Evidence review for combined pharmacological and non-pharmacological treatments review

National Guideline Centre (UK)

Evidence review for combined pharmacological and non-pharmacological treatments review

Attention deficit hyperactivity disorder: diagnosis and management

Evidence review F

NICE Guideline, No. 87

Authors

National Guideline Centre (UK).

London: National Institute for Health and Care Excellence (NICE); 2018 Mar.

ISBN-13: 978-1-4731-2830-9

1. Combined pharmacological and non-pharmacological treatments

1.1. Review question: What is the most clinically and costeffective combination of pharmacological and nonpharmacological treatment for people with ADHD?

1.2. Introduction

Combining medication and non-pharmacological therapy has the potential to increase effectiveness compared with one treatment alone. In people with ADHD combining treatments may increase effects on core ADHD symptoms through the interaction of the two approaches. The potential value of combining medication and non-pharmacological therapy for people with ADHD might lead to beneficial effects in different domains. For example, medication targeting the core ADHD symptoms such as inattention and hyperactivity/impulsivity, and psychosocial interventions targeting secondary problems and coexisting conditions associated with ADHD. Combining pharmacological and non-pharmacological approaches may also have the potential to deliver both immediate effects on ADHD symptoms through medication, along with more long-lasting effects through the development of behavioural and cognitive skills and strategies. This review evaluates the evidence on the use of combined interventions where medication and non-pharmacological therapies are used together to treat ADHD and while the two approaches are complimentary head to head comparisons between the two are evaluated.

This review should be read alongside evidence review C on pharmacological efficacy and sequencing, evidence report D on pharmacological safety and evidence report E on non-pharmacological efficacy and adverse events.

1.3. PICO table

For full details see the review protocol in appendix A.

Table 1

PICO characteristics of review question.

1.4. Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual.⁴⁶ Methods specific to this review question are described in the review protocol in appendix A.

Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy.

Evidence was divided into the following categories:

Non-pharmacological treatments versus pharmacological treatments
Combined treatments versus non-pharmacological treatments
Combined treatments versus pharmacological treatments
Combined treatments versus no treatment/treatment as usual
Combined treatments versus any other combined treatment

Studies were not included if they systematically selected a population who were responders to the primary treatment under investigation (for example a population of only responders to methylphenidate randomised to CBT alone or CBT with methylphenidate).

Evidence was separated into short term (under 3 months) and longer term (greater than 3 months. Evidence was also separated into whether the outcomes were assessed at the end of treatment (post-treatment (PT)) or at the end of a follow-up period beyond the treatment (follow-up (FU)).

A network meta-analysis was considered for this question but deemed inappropriate due to concerns over differences in trial populations, exact trial interventions and insufficient data available for the relevant outcomes (see the methodology chapter for further details). Although it was not deemed appropriate to conduct an NMA across the entirety of the clinical review, in order to pragmatically obtain the best possible evidence for the select areas in which health economic modelling was feasible and a high priority, a more restricted NMA was conducted. Please see Appendix 3 for more information

1.5. Clinical evidence

1.5.1. Included studies

Thirty-three studies (in 35 publications) were included in the review;¹^,³^,⁹^–¹³^,¹⁷^,²⁰^,²¹^,²⁴^,²⁶^,²⁸^,³⁴^,³⁶^–³⁸^,⁴¹^,⁴³^,⁴⁴^,⁴⁹^–⁵²^,⁵⁴^–⁵⁶^,⁵⁹^,⁶¹^–⁶³^,⁶⁵^–⁶⁸ these are summarised in Table 2 and Table 3 below. Evidence from these studies is summarised in the clinical evidence summary tables below.

See also the study selection flow chart in appendix C, study evidence tables in appendix D, forest plots in appendix E and GRADE tables in appendix F.

There were 0 studies in the under 5 year old category 23 studies in the 5 to 18 year old category and 10 studies in >18 year old category.

The majority of studies (n=23) compared combination to pharmacological interventions, 13 compared combination to non-pharmacological interventions, 8 compared pharmacological to non-pharmacological, 4 compared combination to usual care and 1 compared combination to another combination.

A number of studies included more than two arms and therefore contributed to more than one comparison.

1.5.2. Excluded studies

See the excluded studies list in appendix I.

1.5.3. Summary of clinical studies included in the evidence review

Table 2

Summary of studies included in the evidence review for children aged over 5 to 18.

Table 3

Summary of studies included in the evidence review for adults.

See appendix D for full evidence tables.

1.5.4. Quality assessment of clinical studies included in the evidence review

1.5.4.1. Children and young people aged 5 to 18

1.5.4.1.1. Pharmacological treatment versus non-pharmacological treatment in children and young people

Table 4

Clinical evidence summary: Atomoxetine versus parent/family training.

Table 5

Clinical evidence summary: Stimulants versus exercise.

Table 6

Clinical evidence summary: Stimulants versus Neurofeedback.

Table 7

Clinical evidence summary: Stimulants + non-specific supportive therapy versus stimulants.

Table 8

Clinical evidence summary: Mixed medication versus parent/family training.

1.5.4.1.2. Combination versus non-pharmacological treatment in children and young people

Table 9

Clinical evidence summary: Atomoxetine + parent/family training versus parent/family training.

Table 10

Clinical evidence summary: Atomoxetine + PE versus PE.

Table 11

Clinical evidence summary: Atomoxetine + CBT versus CBT.

Table 12

Clinical evidence summary: Stimulants + NF versus NF.

Table 13

Clinical evidence summary: Stimulants + CBT versus CBT.

Table 14

Clinical evidence summary: Mixed medication + PT/FT versus PT/FT.

1.5.4.1.3. Combination versus pharmacological treatment in children and young people

Table 15

Clinical evidence summary: Atomoxetine + PT/FT versus atomoxetine.

Table 16

Clinical evidence summary: Stimulants + PT/FT versus stimulants.

Table 17

Clinical evidence summary: Stimulants + PT/FT versus stimulants + NSST.

Table 18

Clinical evidence summary: Stimulants + attention/memory/cognitive training compared to stimulants.

Table 19

Clinical evidence summary: Stimulants + NF versus stimulants.

Table 20

Clinical evidence summary: Mixed medication + PT/FT versus mixed medication.

Table 21

Clinical evidence summary: Mixed medication + CBT versus mixed medication.

Table 22

Clinical evidence summary: Mixed medication + PE versus mixed medication + NSST.

Table 23

Clinical evidence summary: Mixed medication + sleep intervention versus mixed medication.

Table 24

Clinical evidence summary: Mixed medication + NF compared to mixed medication.

1.5.4.1.4. Combination versus no treatment/usual care in children and young people

Table 25

Clinical evidence summary: Atomoxetine + PT/FT versus placebo/usual care.

Table 26

Clinical evidence summary: Mixed medication + PT/FT versus placebo/usual care.

1.5.4.1.5. Combination versus other combined treatments in children and young people

Table 27

Clinical evidence summary: Stimulants + NF versus stimulants + attention/memory/cognitive training.

1.5.4.2. Adults over the age of 18

1.5.4.2.1. Pharmacological treatment versus non-pharmacological treatment in adults

Table 28

Clinical evidence summary: stimulants + NSST versus CBT.

1.5.4.2.2. Combination versus non-pharmacological treatment in adults

Table 29

Clinical evidence summary: stimulants + CBT/DBT versus CBT/DBT alone.

Table 30

Clinical evidence summary: stimulants + CBT/DBT + PT/FT versus NSST + PT/FT alone.

1.5.4.2.3. Combination versus pharmacological treatment in adults

Table 31

Clinical evidence summary: stimulants + CBT/DBT versus stimulants + NSST alone.

Table 32

Clinical evidence summary: mixed medication + CBT/DBT versus mixed medication alone.

Table 33

Clinical evidence summary: mixed medication + CBT/DBT versus mixed medication + NSST.

1.5.4.2.4. Combination versus no treatment/usual care in adults

Table 34

Clinical evidence summary: Stimulants + CBT/DBT compared to NSST alone.

See appendix F for full GRADE tables.

1.6. Economic evidence

1.6.1. Included studies

2008 guideline literature

One original model from CG72 in adults, looking at a combination of pharmacological and non-pharmacological treatments is included.

Details of the combination model in adults can be found in Table 35.

Published literature

No relevant health economic studies were identified from the update search.

See also the health economic study selection flow chart in Appendix C.

1.6.2. Excluded studies

Four studies were included in CG72 that could be included in the combination review. All were in children.¹⁸^,²⁹^,³¹^,³⁹^,⁶⁹

All of these studies have been selectively excluded due to limited applicability and/or methodological limitations. These are listed in Appendix I, with reasons for exclusion given.

One original model from CG72 in children, looking at a combination of pharmacological and non-pharmacological treatments, has been selectively excluded because the clinical evidence feeding into this model is not included in the guideline clinical review (see Appendix I for more details), and will also be superseded by original modelling in children for this question.

See also the health economic study selection flow chart in appendix G.

1.6.3. Summary of studies included in the economic evidence review

Table 35

Health economic evidence profile: CBT added to medication versus medication alone in adults on medication but with clinically significant symptoms.

Table 36

Health economic evidence profile: combination of Atomoxetine + behavioural therapy versus atomoxetine versus behavioural therapy, in children.

Table 37

Health economic evidence profile: Methylphenidate + self-help behavioural therapy versus methylphenidate, in children on methylphenidate but with functional impairment.

Table 38

Health economic evidence profile: Medication + CBT versus medication, in adolescents on medication but with clinically significant symptoms.

1.6.4. Health economic model

The previous guideline model evaluating combination treatments in comparison to medication alone or behavioural therapy alone, in children, was based on two studies that directly compared the three interventions. The focus was on stimulants as the medication. The question on combination treatments was decided as the first priority for economic modelling because there is a highly relevant trade-off with regards to whether the benefit of any additional interventions are worth the additional cost. It is also considered highly important in mental health for patients to have choices about what treatments they might prefer. Therefore, updating the previous model which sought to compare different types of treatments as well as the combination of the two, would help inform; the treatment pathway to be recommended as to whether there is a hierarchy regarding pharmacological and non-pharmacological treatments, and also whether the combination is cost effective.

There are three models replacing the previous combination model in children, as the clinical data identified from the combination review that had dichotomous outcomes needed for any models was sparse and the committee felt that some interventions couldn’t be combined together. An overview of the 3 models and their results are discussed below, with further detail in the write-up (Appendix 1).

1. Atomoxetine combination model

Model overview

Being evaluated in the model is the combination of Atomoxetine and (group) behavioural therapy, compared to Atomoxetine alone and behavioural therapy alone.

The model is a decision tree with a 1 year time horizon. Atomoxetine dose in the model is using a maintenance dose of 1.2mg/kg per day. Behavioural therapy consists of 10 weekly sessions of 1 hour of parent training with a clinical psychologist (in keeping with the behavioural therapy resource use in the parent training model). Combination treatment is the sum of both these interventions.

The population is children with ADHD, with an age range of 5-15 from the studies informing effect, with average ages of 8-11. They are mixed populations in the sense that some people in the trials have tried medication before, but there is no selective inclusion based only on previous non-response. Because patients begin treatment when they enter they model (as that was how the trials were set up) then in the interventions that include atomoxetine, there is a probability of withdrawal from the treatment because of intolerable side effects. At the end of duration of the trials (10 weeks), patients from all the treatments are either classified as responders or non-responders. Responders remain on the treatment (if it involves atomoxetine, because behavioural therapy is a short term treatment) and remain responding until the end of the model. Patients can also experience adverse events that are tolerable and do not cause them to withdraw from the treatment, but do lead to a decrement in quality of life. If a patient withdraws because of adverse events, or does not respond to the treatment and therefore stops the treatment, then they go on to what is referred to as ‘other treatment’. There are no adverse events assumed from behavioural therapy.

No further lines of treatment were modelled because assumptions would be needed about what these would be, and there is a lack of data on probabilities that are dependent on prior treatment choices. An overarching state of ‘other treatment’ was used as a catch-all to represent other treatment that patients might go on to, i.e. an overall probability of response in the general ADHD child population in which some people may be on a variety of treatments and some people may not be on any active treatment. The cost of ‘other treatment’ is represented only in terms of resource use (the number of consultations associated with responders and non-responders). This is because resource use in terms of staff consultations (with a psychiatrist or nurse) is already included as a key part of the cost of starting and continuing Atomoxetine, and therefore it made sense to continue including this resource use for the whole time horizon of the model so as not to bias against Atomoxetine or for not responding to be a cheaper outcome.

Data

3 studies inform the treatment effect of this model, with an average trial duration of 10 weeks. One comparing all 3 comparisons²¹, one comparing the combination with atomoxetine alone⁶⁵, and one study compared the combination with behavioural therapy alone⁵⁸. Note that where an intervention from the studies had a placebo pill in combination with a behavioural therapy; for the purposes of the model this is being treated as only behavioural therapy. The studies had some differences in terms of intensity of treatments, population medication status, and scales used to define response. But they were combined because they included atomoxetine as the drug. The probabilities of response for each intervention were derived from a network meta-analysis of the three studies undertaken by the health economist for to inform the model. Probability of discontinuation and adverse events was taken from the guideline clinical review.

Resource use such as doses of atomoxetine during titration and maintenance, and staff costs associated with monitoring treatments as well as the staff costs associated with behavioural therapy were elicited from the committee. Utilities were from the same source as the parent training model, as for all the models in the guideline. The utility gain from response is assumed to increase linearly over the trial period to reflect that the effect may not be immediate.

Results

The probabilistic base case results showed that behavioural therapy was the most cost effective because it had the highest net benefit, and also the ICERS of Atomoxetine compared to behavioural therapy (£44,175 per QALY), and combination treatment compared to Atomoxetine (£56,219 per QALY) were above the threshold of £20,000, demonstrating that the additional benefit does not justify the cost of the more expensive interventions.

Various sensitivity analyses were also explored; assuming the response from behavioural therapy decreases linearly from the end of treatment to end of the model for BT alone and combination arms. This showed behavioural therapy still had the highest net benefit, but atomoxetine had a lower ICER than in the base case. This is because reducing the effectiveness of behavioural therapy led to lower total QALYs for the other interventions. Another sensitivity analysis assumed behavioural therapy was individual rather than a group treatment; this increased the cost of the intervention to the extent that behavioural therapy was dominated by atomoxetine. Atomoxetine was now the most cost effective intervention because combination treatment had a very high ICER compared to atomoxetine (£399,620). A final sensitivity analysis also looked at using alternative sources of utility other than the EQ-5D. This showed that although the results were sensitive to changes in the QALY, behavioural therapy still had the highest net benefit.

This model aimed to compare the cost effectiveness of starting a combination of Atomoxetine and behavioural therapy, compared to starting Atomoxetine alone, or a course of behavioural therapy. Although Atomoxetine is a drug that would most likely not be at the beginning of the treatment pathway, the interventions included in the model are comparisons that were identified in the clinical review that had appropriate outcomes that could be utilised in a model. Therefore what the model is really answering is; in children who may be considering using atomoxetine, is it cost effective alone, or in combination with behavioural therapy, or is behavioural therapy alone the best choice in terms of cost effectiveness. What conclusions can be drawn from the model are highly dependent on the clinical data used, and the assumptions made about future pathways in the model and inputs such as resource use.

Limitations include; the clinical effect only being based on 3 studies. Bringing together the conclusions of dichotomous outcomes (what this model is based on) with the clinical review that used continuous outcomes is also a challenge as the two types of outcomes do not always agree. The committee opinion was that the clinical review in general is unlikely to have captured all the benefits of non-pharmacolgical treatment, because these are wider than just ADHD core symptoms. Other benefits also may not have been captured such as longer term impacts which are unknown, and the impact on other sectors. It was not possible to model all treatments individually and in sequences compared to each other and so assumptions (or the lack of) made about further treatment is also a limitation.

2. MPH + self-help behavioural therapy model

Model overview

This model is comparing staying on MPH if you are a partial responder versus adding telephone assisted self-help behavioural therapy in children. The model is interested in the added value of a behavioural therapy on top of medication. The intervention involved parents reading 8 self-help booklets dealing with disruptive behaviour disorders and parenting that were mailed to them approximately every 2 weeks. Parents received 10 phone consultations of about 30 minutes each in the first 6 months, and then 4 booster calls during the second 6 months.

The population is children with ADHD who are on a stable dose of MPH, but had functional impairment (in the study this was functional impairment in at least one of the domains of the Weiss Functional Impairment Rating Scale). This can be seen as the baseline population because children are on MPH in both the intervention and the control group.

This is based on a single study reporting outcomes at 12 months. The GC thought that analysing the cost effectiveness of this study would be useful because it is an intervention they envisaged could be used as a baseline intervention in current practice because; it is more longer term than the usual courses of behavioural therapy, it involves self-help and telephone consultations. Although, as the intervention will be provided on an individual basis, the cost of the behavioural therapy is likely to be high.

The model is a decision tree model with a 1 year time horizon. Children enter the model being stable on methylphenidate, and can either remain on methylphenidate or add behavioural therapy. As the model is using a time horizon of 12 months and the trial data is also 12 months long – no assumptions need to be made beyond 12 months about what patients might then go on to.

Data

As mentioned above clinical data is based on a single study.⁹ The only costs included in the model are the costs of the behavioural therapy, as any other costs are assumed to be common to the both arms. Utilities are also from the same source as the other models, with additional sources being tested in a sensitivity analysis. The utility gain from response is assumed to increase linearly over the trial period to reflect that the effect may not be immediate. The response probabilities are derived from analysis in Winbugs software which gave simulations of baseline and treatment response probabilities to use in the PSA.

Results

The probabilistic base case results showed the ICER of the intervention to be very high (£114,803). The additional benefit from the intervention cannot justify the additional cost of providing the intervention. It is a resource intensive intervention on top of medication because staff time spent on the phone is needed which means the intervention is provided on an individual basis.

A threshold analysis on costs showed that the cost of the intervention would have to be around 17% what it is in the base case to make the intervention cost effective, which is a significant reduction. This would equate to somewhere between two to three 30 minute phone calls. A threshold analysis on QALYs showed that the incremental QALY would need to go from 0.0076 to 0.0434 to make the intervention cost effective. Varying the time horizon found that the effect would have to be stable after the intervention ended up to at least 3 years to make the intervention cost effective. When varying both the time horizon and the utility gain simultaneously, this also showed that around 3.5 years at minimum (regardless of changes in utility gain) would be needed for the ICER to be under £20,000 per QALY. A 2-way sensitivity analysis varying both the baseline response probability and the intervention response relative risk showed that there is not any level of combination of baseline risk and relative risk that would make the intervention cost effective. Varying the utility values using different sources also showed that the model was sensitive to QALYs but the ICERs still remained high.

When assuming the effect increases linearly to 6 months (as the phone calls are more intense up until that point), and stays at that level until 12 months, as opposed to increasing linearly to 12 months; This showed that although the ICER fell, it was still above the NICE threshold because although there is a higher incremental QALY, this is still not high enough to justify the cost.

The results have to be interpreted with caution, because the model is only comparing the addition of a self-help non-pharmacological intervention on top of what was used as a baseline in the study (on MPH). It does not tell us about what else might be cost effective that a patient could add or switch to if they are a partial responder, only that what we have investigated as an addition is not cost effective. It also needs to be interpreted with caution as to whether the results can be extrapolated to other treatments that patients might only be partially responding to. But given the 2-way sensitivity analysis, we can be fairly confident that even another treatment with a higher baseline response rate or higher relative risk wold still not improve the ICER to a level considered cost effective.

This model is not without its limitations. It is only based on a single study. It can be difficult to also marry-up the conclusions of the model with what might be interpreted from the clinical review about the interventions in question. On a continuous scale, the improvements may be more subtle and there could still be an improvement in quality of life even if someone hasn’t gone from non-response to response. For the study this model is based on (Dose 2016), the clinical review did not find the intervention clinically effective based on continuous outcomes (using the guideline cut-off of >20% of the control group risk). However, using the clinical review MID for dichotomous outcomes implies that the intervention has clinical benefit. Therefore the two outcomes are in conflict here. The committee opinion was that the clinical review in general is unlikely to have captured all the benefits of non-pharmacolgical treatment, because these are wider than just ADHD core symptoms. Other benefits also may not have been captured such as longer term impacts which are unknown, and the impact on other sectors. Structural assumptions keeping the model simple are also a limitation.

3. Medication + CBT model

Model overview

This model is comparing staying on medication if you are a partial responder versus adding (individual) CBT. The model is therefore interested in the added value of CBT on top of medication. The population are adolescents who are on a stable dose of medication for the last 2 months (medication is stated as an FDA approved medication for ADHD), but have clinically significant symptoms as rated by a CGI-S rating of 3 or above.

The intervention involved 12 sessions of individual CBT, and two additional parent only sessions were offered.

A with the previous models, the model is a decision tree model with a 1 year time horizon. Patients who enter the model are already on medication but have some clinically significant symptoms. Patients can either stay on their medication or add CBT on top of their medication. Outcomes are in terms of response or no response at the 4 month time-point because that was the length of the trial.

Data

This is based on a single study reporting outcomes at 4 months.⁵⁵

The effect is extrapolated from 4 months to the end of the model (12 months). As the medication the adolescents are currently on is assumed to be the baseline or current practice, then this applies for the whole time horizon of the model. Everyone in the baseline arm of the model stays on the baseline for the whole time period regardless of whether they respond or not. It was decided to extrapolate the effects from the trial and not make further assumptions about what treatments people might go on to following the end of the trial period, as this would involve too many assumptions. It was felt that this would be a larger omission from a model that compared a drug to a non-drug comparison directly (like the ATX model), whereas here we are interested in the addition of an intervention to a common baseline. Because of the baseline applying to both arms it may also be argued that costs are likely to be similar for both arms even if people change treatments over time – unless they change to different treatments or at different times because of the intervention itself, but we had no information on this.

The response probabilities are derived from analysis in Winbugs software which gave simulations of baseline and treatment response probabilities to use in the PSA.

The only costs included in the model are the costs of CBT. The source for utility data is the same as has been used in all the models in this guideline. The utility gain from response is assumed to increase linearly over the trial period to reflect that the effect may not be immediate.

Results

The probabilistic base case results show that the addition of CBT is not cost effective (ICER of £62,007 per QALY). This is mostly down to the high cost of the intervention per person because it is individual rather than group format.

Various sensitivity analyses were conducted; one sensitivity analysis assumed that the effect of CBT diminishes and linearly decreases down from 4 months when the intervention ends to 12 months. This showed that the ICER increased to £105,192 per QALY because the incremental QALYs fell.

Threshold analyses showed that the number of sessions that would need to be provided to make the intervention cost effective would be between 3 and 4 – assuming the same level of effect. The incremental QALY between the intervention and comparison would need to be 0.0582 (base case 0.0188) to make the intervention cost effective. The time horizon of the model would also have to be almost 3 years to make the intervention cost effective, all other things being equal, again assuming the effect post treatment is maintained.

A 2-way sensitivity analysis varying both the baseline response probability and the intervention response relative risk showed that there is not any level of combination of baseline risk and relative risk that would make the intervention cost effective (assuming all other things the same like the base case cost). A 2-way sensitivity analysis varying both the time horizon of the model and the utility gain of responders over non-responders showed that the intervention is cost effective with a shorter time horizon if the incremental utility gain is higher, as expected. Please see Appendix 2 for more details. Finally, varying the utility values using different sources also showed that the model was sensitive to QALYs but the ICERs still remained high.

The model needs to be interpreted with caution because it can only be inferred that the addition of individual CBT is not cost effective compared to staying on something that you are only partially responding to. It is not providing any information on what other treatments might be more cost effective. There are likely to be other treatments that are more cost effective than adding CBT.

Limitations include (which are very similar to those of the previous model); the model is only based on a single study with a small population. There is somewhat of a discord between the data that the models use and the data that the clinical review extracted. As mentioned in the limitations section of the previous model – it may be that the improvements on a continuous scale may be more subtle and there could still be an improvement in quality of life even if someone hasn’t gone from non-response to response. From the clinical review using continuous outcomes; the study used in this model showed that the addition of individual CBT to mixed medication has a clinically important benefit. This agrees with the dichotomous outcome. Even though the two outcome types agree, it still remains that even though an intervention might be effective it isn’t effective enough to make it cost effective. The committee opinion was that the clinical review in general is unlikely to have captured all the benefits of non-pharmacolgical treatment, because these are wider than just ADHD core symptoms. Other benefits also may not have been captured such as longer term impacts which are unknown, and the iimpact on other sectors. The structural assumptions the model has made about not including assumptions about further treatment can be seen as a limitation if in fact the addition of CBT has an impact on underlying resource use.

See Table 36, Table 37 and Table 38 for summaries of all three models.

1.6.5. Unit costs

Drug costs

Relevant unit costs are provided below to aid consideration of cost-effectiveness. The drugs listed below are based on those identified from the clinical review as well as those commonly used even if the review did not find evidence on them, and therefore do not include the entire list of interventions from the protocol.

The costs below are illustrative. For the commonly used ADHD drugs; a low and high dose has been demonstrated and taken from the BNF. Some doses were not taken from the BNF and the reason for this is highlighted. Advice has also been taken from the BNF about whether a single dose per day or the doses can be divided, where available. For drugs that are not used for ADHD then the clinical review was used for dosing information.

Note that there can be various branded generic versions of a drug, but drugs of the same class with the same dose have the same cost in the drug tariff regardless of who manufactures it.

Table 39

UK costs of ADHD drugs for children.

Table 40

UK costs of ADHD drugs for adults.

The pricing structure of the different drugs can also impact the overall cost, as if you are taking a higher dose and you could do this once a day, then a higher dose tablet tends to be cheaper than taking two tablets of half the dose. So with most drugs there are economies of scale of the higher formulations. This isn’t always the case though. With some drugs it is possible to take only one tablet a day, such as the modified release versions, but with others you would need to take tablets at multiple points in the day, which means more pills per day of lower formulations.

Costs of other healthcare resource such as hospital appointments that may differ by intervention are illustrated below.

Other resource use

Table 41

Staff costs associated with selecting and monitoring medication treatment.

For example, people on stimulants may see healthcare professionals more frequently in the beginning in order to make sure the dose is appropriate and then may see healthcare professionals less frequently.

Non pharmacological treatment costs

Highlighted below are some costs associated with non-pharmacological treatment. Table 41 shows the costs of individual staff that may be providing treatment such as behavioural therapy/cognitive behavioural therapy

Costs can vary depending on the band of person providing the treatment. It is also common for the clinician to have an assistant to help with the administration and setting up of the training. The relevant bands for the respective roles were derived from the guideline committee when identifying the inputs for the parent training model.

Table 42

Staff costs associated with behavioural therapy.

The total costs of a course of treatment per person depend upon the number of sessions, whether it is a group or individual course, how much preparation is needed, the band of staff involved, and also the individual components that might make up the course (e.g. if training is also provided for family members/teachers (if children)).

Published costs

Some illustrations of specific costs of behavioural therapy training are provided below from the PSSRU;

Table 43

Published PSSRU costs on cognitive behavioural treatments.

1.7. Resource impact

We do not expect recommendations resulting from this review area to have a significant impact on resources.

1.8. Evidence statements

1.8.1. Clinical evidence statements

Children and young people aged 5 to 18

Atomoxetine versus PT/FT

No evidence for quality of life, clinical global impression scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality) and clinical global impressions scale (PT; 1 study very low quality).
There was no clinically important benefit for ADHD symptoms total (PT parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality), ADHD hyperactivity symptoms (PT teacher rated; 1 study very low quality) and ADHD inattention symptoms (PT parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality).

Stimulants versus Exercise

No evidence for quality of life, ADHD symptoms total, clinical global impression scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study low quality) and ADHD inattention symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study moderate quality).

Stimulants versus NF

No evidence for quality of life, clinical global impression scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study low quality) and ADHD inattention symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study low quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality) (FU teacher rated; 1 study very low quality), ADHD hyperactivity symptoms (PT teacher rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT self-rated; 2 studies very low quality) (FU self-rated; 1 study very low quality), ADHD inattention symptoms (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (FU teacher rated; 1 study very low quality) (PT self-rated; 1 study very low quality) (FU self-rated; 1 study very low quality) and academic performance (PT self-rated; 1 study very low quality) (FU self-rated; 1 study very low quality).
There was a clinically important harm for ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality) (FU teacher rated; 1 study very low quality), ADHD inattention symptoms (PT teacher rated; 1 study very low quality) (PT self-rated; 1 study very low quality) and academic performance (PT self-rated; 1 study very low quality).

Stimulants + NSST versus stimulants

No evidence for quality of life, ADHD symptoms total, ADHD inattention symptoms, clinical global impression scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT teacher rated; 1 study very low quality) (FU teacher rated; 1 study very low quality).
There were no clinically important benefits for ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality).

Mixed medication versus PT/FT

No evidence for quality of life, clinical global impression scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT teacher rated; 1 study low quality) (PT parent rated; 1 study low quality) (PT observer rated; 1 study low quality) and ADHD inattention symptoms (PT teacher rated; 1 study low quality).
There were no clinically important benefits for ADHD symptoms total (FU teacher/parent rated; 1 study moderate quality), ADHD inattention symptoms (PT parent rated; 1 study low quality), numeracy outcomes (PT observer rated; 2 studies very low to moderate quality) and literacy outcomes (PT observer rated; 2 studies very low to moderate quality) (FU observer rated; 1 study moderate quality).

Combination versus non-pharmacological treatment in children and young people

Atomoxetine + PT/FT versus PT/FT

No evidence for quality of life, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT teacher rated; 1 study low quality), ADHD hyperactivity symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study low quality), ADHD inattention symptoms (PT teacher rated; 1 study low quality) and clinical global impression scale (PT; 1 study low quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study low quality) and ADHD inattention symptoms (PT parent rated; 1 study low quality).

Atomoxetine + PE versus PE

No evidence for clinical global impression scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for quality of life (PT parent rated; 1 study moderate quality), ADHD symptoms total (PT parent rated; 1 study high quality), ADHD hyperactivity symptoms (PT parent rated; 1 study high quality), ADHD inattention symptoms (PT parent rated; 1 study high quality) and academic outcomes (PT parent rated; 1 study moderate quality).

Atomoxetine + CBT versus CBT

No evidence for quality of life, ADHD hyperactivity symptoms, ADHD inattention symptoms, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT self-rated; 1 study low quality).
There was a clinically important harm for ADHD symptoms total (PT parent rated; 1 study low quality) and clinical global impressions scale (PT; 1 study very low quality).

Stimulants + NF versus NF

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT self-rated; 1 study very low quality), ADHD inattention symptoms (FU teacher rated; 1 study very low quality) and academic outcomes (PT self-rated; 1 studies very low quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality) (FU teacher rated; 1 study very low quality), ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality) (FU teacher rated; 1 study very low quality) (FU self-rated; 1 study very low quality), ADHD inattention symptoms (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT self-rated; 1 study very low quality) (FU self-rated; 1 study very low quality) and academic outcomes (FU self-rated; 1 study low quality).
There was a clinically important harm for ADHD hyperactivity symptoms (PT self-rated; 1 study very low quality), ADHD inattention symptoms (PT teacher rated; 1 study very low quality) (PT self-rated; 1 study very low quality) and academic outcomes (PT self-rated; 1 study very low quality).

Stimulants + CBT versus CBT

No evidence for quality of life, ADHD hyperactivity symptoms, ADHD inattention symptoms, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT observer rated; 1 study high quality).

Mixed medication + PT/FT versus PT/FT

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT teacher rated; 1 study low quality) (PT observer rate; 1 study low quality) and ADHD inattention symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study low quality).
There were no clinically important benefits for ADHD symptoms total (FU teacher/parent rated; 1 study moderate quality), numeracy outcomes (PT observer rated ; 2 studies very low to low quality), literacy outcomes (PT observer rated; 2 studies very low to moderate quality) (FU observer rated; 1 study moderate quality).
There was a clinically important harm for ADHD hyperactivity symptoms (PT parent rated; 1 study moderate quality).

Combination versus pharmacological treatment in children and young people

Atomoxetine + PT/FT versus atomoxetine

No evidence for quality of life, discontinuation due to side effects, serious adverse events, minor adverse events, emotional dysregulation, numeracy outcomes and literacy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT teacher rated; 1 study very low quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study very low quality), ADHD hyperactivity symptoms (PT parent rated; 2 studies very low quality) (PT teacher rated; 2 studies very low quality), ADHD inattention symptoms (PT parent rated; 2 studies very low quality) (PT teacher rated; 2 studies very low quality), clinical global impression scale (PT; 2 studies very low quality) and behaviour outcomes (PT teacher rated; 1 study very low quality).

Stimulants + PT/FT versus stimulants

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, emotional dysregulation, numeracy outcomes and literacy outcomes.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT teacher rated; 1 study very low quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 3 studies low quality) (FU parent rated; 1 study low quality) (PT teacher rated; 2 1 study low quality), ADHD hyperactivity symptoms (PT parent rated; 2 studies moderate quality) (FU parent rated; 1 study very low quality) (FU teacher rated; 1 study very low quality), ADHD inattention symptoms (PT parent rated; 1 study low quality) and behavioural outcomes (PT parent rated; 1 study low quality).

Stimulants + PT/FT versus stimulants + NSST

No evidence for quality of life, ADHD symptoms total, ADHD inattention symptoms, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT teacher rated; 1 study low quality).
There was a clinically important harm for ADHD hyperactivity symptoms (FU teacher rated; 1 study very low quality).

Stimulants + attention/memory/cognitive training versus stimulants

No evidence for quality of life, ADHD hyperactivity symptoms, ADHD inattention symptoms, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study low quality).

Stimulants + NF versus stimulants

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality), (PT teacher rated; 1 study very low quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality) (FU teacher rated; 1 study very low quality), ADHD hyperactivity symptoms (FU parent rated; 1 study very low quality) (FU teacher rated; 1 study very low quality) (PT self-rated; 1 study very low quality) (FU self-rated; 1 study very low quality), ADHD inattention symptoms (PT parent rated; 1 study very low quality) (FU parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality) (FU teacher rated; 1 study very low quality) (PT self-rated; 2 studies very low quality) (FU self-rated; 1 study very low quality) and academic outcomes (PT self-rated; 1 study very low quality) (FU self-rated; 1 study very low quality).
There was a clinically important harm for ADHD hyperactivity symptoms (PT self-rated; 1 study very low quality) and academic outcomes (PT self-rated; 1 study very low quality).

Mixed medication + PT/FT versus mixed medication

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events and minor adverse events.
There were no clinically important benefits for ADHD symptoms total (FU parent rated; 1 study very low quality) (FU teacher/parent rated; 1 study moderate quality), ADHD hyperactivity symptoms (PT teacher rated; 3 studies very low to moderate quality) (FU parent rated; 1 study low quality), ADHD inattention symptoms (PT parent rated; 1 study moderate quality) (PT teacher rated; 1 study moderate quality) (FU parent rated; 1 study very low quality), behavioural outcomes (PT teacher rated; 2 studies very low quality), emotional dysregulation (PT teacher rated; 1 study very low quality), numeracy outcomes (PT; 2 studies very low to moderate quality), literacy outcomes (PT; 2 studies very low to moderate quality) (FU; 1 study moderate quality) and academic outcomes (PT teacher rated; 2 studies very low quality).
There was a clinically important harm for ADHD hyperactivity symptoms (PT parent rated; 1 study moderate quality) (PT observer rated; 1 study low quality) and emotional dysregulation (PT teacher rated; 1 study very low quality).

Mixed medication + CBT versus mixed medication

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT self-rated; 2 studies low to moderate quality) (PT parent rated; 2 studies low to moderate quality), ADHD hyperactivity symptoms (PT self-rated; 1 study low quality) (PT parent rated; 1 study low quality) and ADHD inattention symptoms (PT self-rated; 1 study low quality) (PT parent rated; 1 study low quality).

Mixed medication + PE versus mixed medication + NSST

No evidence for quality of life, ADHD symptoms total, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse event and literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT parent rated; 1 study low quality) and ADHD inattention symptoms (PT parent rated; 1 study low quality) (FU parent rated; 1 study low quality).
There were no clinically important benefits for ADHD hyperactivity symptoms (FU parent rated; 1 study low quality), behavioural outcomes (PT parent rated; 1 study low quality) (FU parent rated; 1 study low quality) and emotional dysregulation (PT parent rated; 1 study moderate quality) (FU parent rated; 1 study low quality).

Mixed medication + sleep intervention versus mixed medication

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, emotional dysregulation, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 2 studies very low quality) (PT teacher rated; 2 studies low quality), ADHD hyperactivity symptoms (PT teacher rated; 2 studies very low to low quality) (PT parent rated; 2 studies very low quality), ADHD inattention symptoms (PT parent rated; 2 studies very low quality) (PT teacher rated; 2 studies low quality) and behavioural outcomes (PT teacher rated; 2 studies very low to low quality).

Mixed medication + NF versus mixed medication

No evidence for quality of life, ADHD hyperactivity symptoms, ADHD inattention symptoms, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT teacher rated; 1 study low quality) and behavioural outcomes (PT parent rated; 1 study low quality).

Combination versus no treatment/usual care in children and young people

Atomoxetine + PT/FT versus placebo/usual care

No evidence for quality of life, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality), ADHD hyperactivity symptoms (PT parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality), ADHD inattention symptoms (PT parent rated; 1 study very low quality) (PT teacher rated; 1 study very low quality) and clinical global impressions scale (PT; 1 study very low quality).

Mixed medication + PT/FT versus placebo/usual care

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures and emotional dysregulation.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT teacher rated; 1 study low quality) and ADHD inattention symptoms (PT parent rated; 1 study low quality) (PT teacher rated; 1 study low quality).
There were no clinically important benefits for ADHD symptoms total (PT teacher/parent rated; 1 study moderate quality), ADHD hyperactivity symptoms (PT observer rated; 1 study moderate quality), numeracy outcomes (PT observer rated; 2 studies very low to moderate quality) and literacy outcomes (PT observer rated; 2 studies very low to low quality) (FU observer rated; 1 study moderate quality).
There was a clinically important harm for ADHD hyperactivity symptoms (PT parent rated; 1 study low quality).

Combination versus other combined treatments in children and young people

Stimulants + NF versus stimulants + attention/memory/cognitive training

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, emotional dysregulation, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD inattention symptoms (FU teacher rated; 1 study high quality).
There were no clinically important benefits for ADHD symptoms total (PT parent rated; 1 study moderate quality) (PT teacher rated; 1 study moderate quality) (FU parent rated; 1 study moderate quality) (FU teacher rated; 1 study moderate quality), ADHD hyperactivity symptoms (PT parent rated; 1 study moderate quality) (PT teacher rated; 1 study moderate quality) (FU parent rated; 1 study moderate quality) (FU teacher rated; 1 study moderate quality) and ADHD inattention symptoms (PT parent rated; 1 study moderate quality) (PT teacher rated; 1 study moderate quality) (FU parent rated; 1 study moderate quality).

Adults over the age of 18

Pharmacological treatment versus non-pharmacological treatment in adults

Stimulants + NSST versus CBT

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT self-rated; 1 study low quality) (PT observer rated; 1 study low quality), ADHD hyperactivity symptoms (PT observer rated; 1 study low quality), ADHD inattention symptoms (PT observer rated; 1 study moderate quality) and emotional dysregulation (PT self-rated; 1 study moderate quality).

Combination versus non-pharmacological treatment in adults

Stimulants + CBT/DBT versus CBT/DBT alone

No evidence for quality of life, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT self-rated; 1 study low quality) (PT observer rated; 1 study moderate quality) and clinical global impressions scale (FU; 1 study high quality).
There were no clinically important benefits for ADHD symptoms total (PT self-rated; 1 study low quality) (PT observer rated; 2 studies low quality), ADHD hyperactivity symptoms (PT observer rated; 1 study low quality), ADHD inattention symptoms (PT observer rated; 1 study low quality), emotional dysregulation (PT; 2 studies moderate quality) and clinical global impressions scale (PT; 1 study low quality).
There was a clinically important harm for ADHD symptoms total (PT self-rated; 1 study low quality).

Stimulants + CBT/DBT + PT/FT versus NSST + PT/FT alone

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD hyperactivity symptoms (PT observer rated; 1 study low quality).
There were no clinically important benefits for ADHD symptoms total (PT observer rated; 1 study low quality), ADHD inattention symptoms (PT observer rated; 1 study low quality), child ADHD symptoms total (PT parent rated; 1 study low quality) and emotional dysregulation (PT parent rated; 1 study moderate quality).

Combination versus pharmacological treatment in adults

Stimulants + CBT/DBT versus stimulants + NSST alone

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT self-rated; 1 study moderate quality) (PT observer rated; 1 study moderate quality), ADHD hyperactivity symptoms (PT observer rated; 1 study moderate quality), ADHD inattention symptoms (PT observer rated; 1 study moderate quality) and emotional dysregulation (PT; self-rated 1 study moderate quality).

Mixed medication + CBT/DBT versus mixed medication alone

No evidence for discontinuation due to side effects, serious adverse events, minor adverse events, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for ADHD symptoms total (PT observer rated; 1 study low quality) (PT self-rated; 3 studies very low quality) (FU self-rated; 2 studies very low quality), ADHD hyperactivity symptoms (FU self-rated; 2 studies very low quality), ADHD inattention symptoms (PT self-rated; 2 studies very low quality)(FU self-rated; 2 studies very low quality), clinical global impressions scale (PT; 1 study low quality), emotional dysregulation (PT observer rated; 1 study low quality) (PT self-rated; 1 study very low quality) (FU self-rated; 1 study low quality) and behavioural outcomes (FU; 1 study very low quality).
There were no clinically important benefits for quality of life (PT; 1 study very low quality) (FU; 1 study very low quality), ADHD hyperactivity symptoms (PT self-rated; 2 studies very low quality) and behavioural outcomes (PT; 1 study very low quality).

Mixed medication + CBT/DBT versus mixed medication + NSST

No evidence for discontinuation due to side effects, serious adverse events, minor adverse events, behavioural outcomes, literacy outcomes and numeracy outcomes.
There was a clinically important benefit for clinical global impressions scale (PT; 1 study very low quality).
There were no clinically important benefits for quality of life (PT; 1 study low quality), ADHD symptoms total (PT self-rated 2 studies very low quality) (FU self-rated 1 study very low quality), ADHD hyperactivity symptoms (PT self-rated; 1 study very low quality), ADHD inattention symptoms (PT self-rated; 1 study very low quality) and emotional dysregulation (PT self-rated; 1 study very low quality).

Combination versus no treatment/usual care in adults

Stimulants + CBT/DBT compared to NSST alone

No evidence for quality of life, clinical global impressions scale, discontinuation due to side effects, serious adverse events, minor adverse events, behavioural measures, literacy outcomes and numeracy outcomes.
There were no clinically important benefits for ADHD symptoms total (PT self-rated; 1 study low quality) (PT observer rated; 1 study low quality), ADHD hyperactivity symptoms (PT observer rated; 1 study low quality), ADHD inattention symptoms (PT observer rated; 1 study low quality) and emotional dysregulation (PT self-rated; 1 study moderate quality).

1.8.2. Health economic evidence statements

CG72 evidence

One cost-utility analysis found that medication + individual CBT was not cost effective compared to medication alone, for treating ADHD in adults on medication but with clinically significant symptoms (ICER: £65,279). This analysis was assessed as directly applicable with potentially serious limitations.

Update guideline evidence

One original cost-utility analysis found that behavioural therapy was cost effective (had the highest net benefit) compared to atomoxetine, and a combination of behavioural therapy and atomoxetine, for treating ADHD in children. This analysis was assessed as directly applicable with potentially serious limitations.
One original cost-utility analysis found that Methylphenidate + self-help behavioural therapy was not cost effective compared to methylphenidate alone, for treating ADHD in children on methylphenidate but with functional impairment (ICER: £114,803). This analysis was assessed as directly applicable with potentially serious limitations.
One original cost-utility analysis found that medication + individual CBT was not cost effective compared to medication alone, for treating ADHD in adolescents on medication but with clinically significant symptoms (ICER: £62,007). This analysis was assessed as directly applicable with potentially serious limitations.

1.9. The committee’s discussion of the evidence

1.9.1. Interpreting the evidence

1.9.1.1. The outcomes that matter most

The committee considered quality of life, ADHD symptoms and CGI assessment of response to be critical outcomes. ADHD symptoms were separately considered as total, hyperactivity and inattention subscales. The committee did not prioritise any one subscale. ADHD symptoms were separately considered when reported by self, parent, teacher and investigator. The committee considered that all had their merit but that symptoms reported by teacher or investigator were likely to be the most objective assessment of effect.

The committee considered intervention related discontinuations, serious adverse events, behavioural/functional measures, emotional dysregulation and academic outcomes to be important outcomes.

1.9.1.2. The quality of the evidence

The committee noted that the body of evidence for this review was typically low or very low quality. There was no evidence in children under the age of 5 for this review. There was a larger body of evidence for children aged 5 to 18 than for adults over the age of 18. While there were a large number of studies meeting the criteria for the review, in general they were small studies providing imprecise results and only single studies per outcome.

The overall objective of the review was to compare the broad strategies of pharmacological and non-pharmacological interventions both for ADHD symptoms and behaviour, either in isolation or combination. As the committee agreed that different interventions under the headings of pharmacological and non-pharmacological may well have different effects, as established by the separate specific pharmacological and non-pharmacological reviews, these were kept separate. However it was difficult to determine whether or not conflicting results reported by two or more studies related specifically to the interventions under investigation or other factors that differed between trials (for example the exact previous treatment and response of the participants, the quality and content of usual care).

The committee noted that behavioural outcomes, on which one might expect non-pharmacological interventions to have a greater impact such as the outcomes focusing on behaviour and emotional dysregulation, were less commonly reported than ADHD symptom outcomes.

The committee noted that it is much more challenging to provide a true active control arm for non-pharmacological interventions compared with the use of placebo for pharmacological interventions, therefore the trials included in these reviews were rarely if ever blinded to the non-pharmacological intervention allocation.

The committee acknowledged that these limitations in the design of non-pharmacological treatments could impact on the interpretation of the effectiveness of non-pharmacological treatments.

The committee agreed that the quality of the evidence in the review was not sufficient to make strong recommendations about specific combinations of any interventions.

1.9.1.3. Benefits and harms

Overall (and children aged 5 to 18)

Overall the committee agreed that the evidence supported the following statements. Direct comparisons of pharmacological treatment with non-pharmacological treatment showed a benefit for pharmacological treatment, principally in terms of ADHD symptoms. Combined treatments showed a benefit in ADHD symptoms over either pharmacological treatment or non-pharmacological treatment in isolation, this benefit was larger and more consistently observed when compared with non-pharmacological treatment, although the benefit did not consistently equate to a clinically important difference as per the committee’s previously agreed thresholds. Combined treatments showed a benefit in ADHD symptoms compared to no active intervention or usual care. No comparison between any two combined treatments showed a clear picture of consistent clinically important benefit. The committee noted that although the above was an appropriate summary of the evidence, there were many comparisons showing no clinical difference and relatively frequent inconsistencies across the evidence base.

The benefits from the HE modelling were as follows: in the child atomoxetine combination model, total QALYS were as follows; behavioural therapy: 0.773, Atomoxetine: 0.790, combination treatment: 0.794. In the child methylphenidate + self-help behavioural therapy model, total QALYs were 0.7648 in the intervention arm (combination), and 0.7573 in the comparator arm. In the adolescent CBT combination model, total QALYs were 0.7748 in the intervention arm (combination), and 0.7561 in the comparator arm.

The committee noted that although it was not entirely clear from the evidence base, theoretically non-pharmacological treatments and pharmacological treatments are likely to be effective at targeting different aspects of ADHD. Pharmacological treatments may be better for treating the core symptoms of ADHD whereas non-pharmacological treatments may be more beneficial for improving the functional status of people with ADHD.

Before considering whether any treatment at all is necessary for ADHD symptoms, the committee recommended that appropriate environmental modifications were in place – in some situations this may be all that is required to address the impact of milder ADHD symptoms.

The committee noted that any treatment choice for ADHD is associated with potential harms. Drugs are often considered to be ‘more harmful’ (see the pharmacological adverse events review for more detail on specific adverse effects of various drug options), however non-pharmacological treatments may have specific harms of their own (for example for people who feel stigmatised by having to undergo parent training) and if a person’s treatment choice is not optimised to reduce their ADHD symptoms, there is harm from under treatment.

Children under the age of 5

There was no evidence identified in this review for this population. The committee agreed that the effects seen in children aged 5 to 18 were likely to be similar in the under 5 age group, however the committee noted that concerns around the adverse effects of medication in this younger age group.

Adults aged over 18

The committee noted that the studies in the combination review and non-pharmacological review in this age group focused heavily on CBT. CBT was specifically recommended in the previous guideline as the non-pharmacological intervention of choice in adults with ADHD. The non-pharmacological review supported the finding that CBT had a benefit for ADHD symptoms when compared with no intervention or usual care. However both reviews showed little difference between CBT and a non-specific supportive therapy. The committee was keen to emphasise that this did not imply a lack of efficacy of CBT and noted that the non-specific supportive therapies typically involved regular periods of face to face counselling. The committee agreed that this suggested that CBT is effective but that for some people, it may be possible to achieve similar benefits with structured programs that do not necessarily adhere to the principles of CBT.

Subgroups

There was insufficient evidence in this review to inform specific recommendations about subgroups of people with ADHD, either based on the severity of their symptoms or on any co-existing disorders.

Given the health economic evidence and the previous guideline recommendations, the committee agreed that it was appropriate to make consensus based recommendations on which groups may benefit from a combined approach. In children and young people, the committee supported the recommendations from the NICE guideline on antisocial behaviour and conduct disorders in children and young people, in which the families of all children with or at high risk of developing ODD/CD should be offered group parent training programmes.

Previous recommendations differentiated between children with mild or moderate ADHD and severe ADHD and suggested different strategies for the two groups. These recommendations were purely consensus based as no evidence existed to support that differentiation. In this update, again no evidence was found to support a differential strategy based on severity. However again the committee’s consensus view was that medication should be reserved for those in whom ADHD was having significant impairment on their life. The committee agreed that as short term adverse effects of medication are well reported compared to other treatment approaches it is difficult to compare harms across treatments, but they are present in people that take medication (as documented in evidence report D on pharmacological safety) and healthcare professionals should only be offering medication to children in whom the risk benefit balance supported this decision. To achieve this aim, the committee recommended that medication should be first line treatment for those in whom environmental modifications had not reduced the impact of ADHD symptoms on at least one area of a child or adults’ everyday life. This categorisation differs from the previous guideline’s use of ‘severe ADHD’ and the committee agreed it was appropriate to focus more on the impact of symptoms as opposed to a diagnostic assessment of severity of disease. Addressing persistent symptoms in one domain is important in this age group, for example, parent/carer training and environmental modification may have reduced impairment in situations and relationships at home but not at school, it is important that the impairment at school is addressed to ensure the child or young person is has the best opportunity to achieve at school.

The committee noted that much of the evidence in this review on atomoxetine in children came from a study specifically looking at children with ADHD and ASD. Few of the pooled comparisons included this evidence but where this was the case – there was no obvious heterogeneity to support a different treatment effect in this population compared to the general population..

1.9.2. Cost effectiveness and resource use

No published economic evidence was identified for this question. Four studies included as economic evidence for this question in the previous guideline have been selectively excluded for reasons of applicability and methodological quality.

The previous guideline conducted two original economic models looking at combination treatments versus individual treatments, one in children and one in adults. The child model has been selectively excluded because it was based on two studies not included in the clinical review, it is however also superseded by three new models on combinations in children. The adult model is included in this update because no new modelling has been undertaken for adults as it was not felt to add value or change the conclusions of the previous model. A summary of the existing adult combination model and new children models can be found below.

The previous model in adults was in a population of adults with ADHD who are stable on medication but have clinically significant symptoms, and compared adding CBT to medication versus staying on medication alone. It was a decision tree model with a 1 year time horizon based on two short terms trials for clinical effect. This found that the addition of CBT was not cost effective with an ICER of £65,279 per QALY. This analysis was rated as directly applicable with potentially serious limitations, such as only based on two trials, extrapolation of effect, and only included intervention costs.

New health economic analysis – Atomoxetine combination model

The previous child model was updated because it was expected there would be new data in children, and the combination questions have economic implications in terms of the trade-off between two interventions together having a large resource impact weighed up against whether the additional effect is enough to make them cost effective. It was discussed whether the effects of two different types of interventions were expected to be additive, and this was not believed to be the case, therefore even if pharmacological treatment is cost effective compared to doing nothing, and non-pharmacological treatment is cost effective compared to doing nothing; we cannot make the assumption that both together would therefore be cost effective. Only dichotomous outcomes could be used for a model to link to quality of life, which automatically reduces the pool of studies that can be used from the clinical review. The studies that had dichotomous outcomes had comparisons that the committee felt couldn’t be combined, particularly around the differences in behavioural treatments for example it would not be appropriate to combine parent training with CBT. This is why the previous child model is being superseded by 3 models.

The first child model compared atomoxetine in combination with behavioural therapy (group parent training), to atomoxetine alone and behavioural therapy alone. This was a decision tree model with a one year time horizon. The population was mixed in terms of some children in the trials having treatment before, but none selected people specifically who were previous non-responders (or responders). Patients could withdraw from adverse events of atomoxetine and the model also included tolerable adverse events that had a utility decrement but treatment continued. Resource use of drugs and behavioural therapy were elicited from the committee. Clinical effectiveness was from 3 studies and these were combined in a network meta-analysis for the model. The probabilistic results showed behavioural therapy was the most cost effective. This was the cheapest and also the least effective intervention, but had the highest net benefit because the ICERs (when comparing an intervention to the next cheapest) were above the NICE £20,000 threshold (Atomoxetine compared to behavioural therapy: £44,175 per QALY, and combination treatment compared to Atomoxetine: £56,219 per QALY). Atomoxetine is more costly than behavioural therapy because of the ongoing monitoring required for each child, whereas the cost of behavioural therapy is spread over a group of children and is only for a short time frame. A sensitivity analysis using individual behavioural therapy costs showed that atomoxetine dominated behavioural therapy, and atomoxetine was the most cost effective compared to combination treatment. Another sensitivity analysis made assumptions about the effect of behavioural therapy diminishing after the treatment duration (10 weeks) and going down to zero by the end of the model (whereas in the base case the responders were assumed to remain responders for the whole time horizon), behavioural therapy still had the highest net benefit. Using different sources of utility values that derived utilities in different ways (such as direct valuation of health states, and using another generic measure instead of the EQ-5D) also did not lead to a different result. This was done to reassure the GC about the sensitivity of the EQ-5D, which it was debated is perhaps inappropriate for this condition, but there is no empirical evidence to support this. This analysis was assessed as directly applicable with potentially serious limitations. This is because it is only based on a small number of trials, no assumptions were made about further lines of treatment and so the costs and QALYs may be being underestimated because a non-responder will most likely find other treatments that work for them to accrue QALYs and costs. Also, the committee highlighted that the effectiveness of non-pharmacological treatments is not well captured in trials and may be underestimated.

New health economic analysis – Methylphenidate + self-help telephone BT model

The second model compared methylphenidate with the addition of telephone self-help behavioural therapy versus methylphenidate alone, in a population of children who are partial responders to methylphenidate (i.e. from the single clinical study used for effect this is specifically children who are stable on methylphenidate but have some functional impairment). This was a decision tree model with a 1 year time horizon. The clinical study used for effect had 12 month outcomes. No adverse events or costs of methylphenidate were included because this was the baseline common to both arms. Only intervention costs of the behavioural therapy were included. Probabilistic results showed that the addition of the behavioural therapy was highly cost ineffective (ICER = £114,803 per QALY). The incremental cost was high because this is an individual therapy. The incremental QALY was also small because the difference in response probabilities between the comparisons was quite small. Threshold analyses showed that the cost of the intervention would have to be significantly smaller to make the intervention cost effective. See appendix 2 for further detail on other threshold analyses undertaken. A 2-way sensitivity analysis varying the treatment effect and baseline probability showed that no combination of baseline and treatment effect would make the intervention cost effective, all other things being equal. As with the previous model, different utility sources were used, and the effect increased linearly to 6 months and remained at that level (as the phone calls were more intense up to that point) rather than increasing linearly to 12 months. Neither of these sensitivity analyses changed the conclusions. This analysis was assessed as directly applicable with potentially serious limitations. Similarly to the last model; effect is only based on a small sample of data – one study, effect could have been underestimated, and the structure has been kept simple.

New health economic analysis – medication + CBT model

The third model compared medication with the addition of individual CBT versus medication alone. This was in a population of adolescents who were stable on medication but had some clinically significant symptoms. This was a decision tree model with a 1 year time horizon. No adverse events or costs of medication were included because this was the baseline common to both arms. Only intervention costs of CBT were included. The effectiveness of the comparisons was informed by a single study with trial duration of 4 months. Probabilistic results showed that the addition of the individual CBT was not cost effective (ICER = £62,007 per QALY) the incremental cost was again high because the intervention is individual and consists of 12 sessions. The cost of the intervention would need to be below around 32% of the base case cost to make the intervention cost effective. This equates to around 3 to 4 sessions or about 6 hours of CBT. The time horizon of the mode would need to be around 3 years to make the intervention cost effective. A 2-way sensitivity analysis of baseline and treatment effect showed that only with a very low baseline risk and very high treatment effect would the intervention be cost effective. If we also assume the effect of the treatment is not maintained the ICER becomes even larger (£105,192 per QALY). This analysis was assessed as directly applicable with potentially serious limitations. As with the previous models; effect is based on a single study, the effect may be being underestimated because trials are not good at capturing wider outcomes that CBT would address, the structure of the model is kept simple and so costs and effects may be being underestimated.

Children under the age of 5

See the non-pharmacological review and rationale for more information about recommendations in this age group. As a summary; medication is not recommended for this age group. The age of the children are considered too young to be medicated. A sensitivity analysis of the parent training model using a study in the under 5 group showed parent training to be cost effective in a group. Combinations are also not recommended in this group.

Children and young people aged over 5

Taking all the three models for children together, it can be concluded that it is uncertain if combination treatments (meaning combinations of pharma and non-pharma) are cost effective, because of their costs and also uncertainty about their treatment effect. If the behavioural therapy component is provided in a group, then this lowers the cost, which can have an impact on the result (this is more applicable however to parent training than it is to CBT – which is usually individual). However this is highly dependent on the treatment effect. The models need to be interpreted carefully because of the specific populations they are in; i.e. the implication in the second and third model is that a combination is being offered second line as they are partial responders to a drug, and also because they are on different drugs it needs to be taken into consideration with a consensus committee view about the ordering of treatments in the pathway. Additionally there is uncertainty as to whether results might be generalisable to other drugs for example.

This review was also about non-pharmacological treatments compared to pharmacological treatments. The only information on cost effectiveness available to us here is the comparison of atomoxetine versus behavioural therapy from the atomoxetine model. This showed that if we assume the effect of behavioural therapy continues, then atomoxetine is not cost effective compared to behavioural therapy. The drug price would have to be very small for atomoxetine to be cost effective because the costs of monitoring a drug far outweigh the costs of the behavioural therapy. If the effect is not maintained after the course has ended then atomoxetine becomes closer to being cost effective. But if the behavioural therapy is individual rather than a group then behavioural therapy is dominated by atomoxetine. However we haven’t included the costs of further treatment to see how this impacts the results, because less people respond on behavioural therapy so a higher proportion of that cohort may end up on more expensive treatments later on, and titrating and monitoring the effect of a drug is resource intensive. So there are downstream trade-offs that we haven’t been able to account for. It is accepted that pharmacological treatments tend to be more effective. There is also more data from the clinical review showing that drugs are effective versus placebo. And published cost effectiveness evidence also showed that drugs are cost effective versus no treatment. Therefore drugs were considered first line and are offered to all people in this age group.

Based on the cost effectiveness evidence showing that combinations are generally not cost effective, the committee did not recommend combinations for everyone (as supported by the atomoxetine model for example). The committee noted that good current practice provided group support for everyone diagnosed with ADHD that provided education about ADHD and provide -social support. Education about the condition was felt to be an important factor that was highlighted in the qualitative support review. The NICE guideline on patient experience highlights that information about your condition is important, and although it may not directly be an intervention and therefore improve health, it has other benefits that may not be captured in a measure like the QALY. The recommendation states that this could be as little as 1 to 2 sessions, and would incur significantly less cost than a full parent training programme.

It was acknowledged however as part of the review of medication (recommendation 1.10.1), that when medication has been optimised and there are still troublesome symptoms impacting on a person’s everyday life the needs of the patient should be further explored.

The results of the 1 year time horizon model on CBT (and also the telephone support model which was also about individualised treatment), that used a subset of clinical data, showed combinations not to be cost effective. However the committee were concerned that the clinical review (not just the model data) was not capturing the full effects of non-pharmacological treatment. The committee agreed that the effectiveness of non-pharmacological treatments on the condition is not well captured in trials. A more global function measure would be required to capture the impact on factors like self esteem, organisation, relationships, coping with ADHD and in general these more wider factors than just purely symptoms of hyperactivity and inattentiveness. Ideally quality of life or also perhaps the Clinical Global Impressions scales (CGI) are more global, but these were not as prominent in the review data as other outcomes that were more ADHD symptoms based.

The committee agreed it is likely there are benefits from behavioural therapies that are not being captured in the model. If t these were measurable and captured this would lead to more responders which would mean more people to accrue a higher quality of life in the model. It was the opinion of the committee therefore that particularly in adolescents, CBT in addition to medication that has been optimised would be effective at targeting those residual symptoms and this is good current practice. Hence despite the models’ conclusions the committee were uncertain about the results and made a recommendation based on their clinical judgement, to consider combinations in certain circumstances.

Adults aged over 18

For adults, medication was recommended as first line. Clinical evidence from the pharmacological review found medication to be effective. Clinical opinion also agreed with this. There is limited cost effectiveness in adults regarding whether pharmacological or non-pharmacological treatment is more cost effective. Extrapolating from the atomoxetine child model – CBT is the most common form of non-pharmacological treatment provided to adults, and so taking the sensitivity analysis from the atomoxetine model where behavioural therapy was individual tells us that medication is likely to be more cost effective, because of the resource use involved in providing individual behavioural therapy. Non-pharmacological treatment was considered however in the recommendations in specific circumstances. The previous guideline model on combination treatment versus medication in adults who are stable on medication but have remaining impairment (which had a 1 year time horizon and used only two studies for effect) found individual CBT to not be cost effective. Although this model was in the right population, in terms of being in partial responders to drugs (as we are not offering combination to everyone), again the previous arguments still stand that it was considered to have limitations because the trials may not be capturing the full effect of the intervention, which would increase response rates and make the intervention more cost effective. The committee agreed that the previous guideline recommendations about considering combinations in a certain group of adults should be carried forward on clinical grounds, as cost effectiveness was uncertain at best, rather than definitive. This is good current practice and not likely to have a resource impact.

1.9.3. Other factors the committee took into account

The committee agreed that the two treatment approaches target different aspects of ADHD and should not be seen as an either or option and treatment should be focused on the person’s needs. The committee noted that in an area where the evidence base is not definitive and the interventions under review have very different benefit and harm profiles, the element of patient choice and preference is of particular importance. The committee noted that people with ADHD who engage with their treatment choice are more likely to gain benefits, regardless of what that treatment choice is.

References

1.: A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Archives of General Psychiatry. 1999; 56(12):1073–1086 [PubMed: 10591283]

2.: Abbasi SH, Heidari S, Mohammadi MR, Tabrizi M, Ghaleiha A, Akhondzadeh S. Acetyl-L-carnitine as an adjunctive therapy in the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a placebo-controlled trial. Child Psychiatry and Human Development. 2011; 42(3):367–375 [PubMed: 21336630]

3.: Abikoff H, Hechtman L, Klein RG, Weiss G, Fleiss K, Etcovitch J et al. Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. Journal of the American Academy of Child and Adolescent Psychiatry. 2004; 43(7):802–811 [PubMed: 15213581]

4.: Aman MG, Bukstein OG, Gadow KD, Arnold LE, Molina BS, McNamara NK et al. What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder? Journal of the American Academy of Child and Adolescent Psychiatry. 2014; 53(1):47–60.e41 [PMC free article: PMC3984501] [PubMed: 24342385]

5.: Aman MG, Hollway JA, Leone S, Masty J, Lindsay R, Nash P et al. Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children. Research in Developmental Disabilities. 2009; 30(2):386–396 [PubMed: 18768293]

6.: Arnold LE, Gadow KD, Farmer CA, Findling RL, Bukstein O, Molina BS et al. Comorbid anxiety and social avoidance in treatment of severe childhood aggression: response to adding risperidone to stimulant and parent training; mediation of disruptive symptom response. Journal of Child and Adolescent Psychopharmacology. 2015; 25(3):203–212 [PMC free article: PMC4403224] [PubMed: 25885010]

7.: Babinski DE, Waxmonsky JG, Pelham WE, Jr. Treating parents with attention-deficit/hyperactivity disorder: the effects of behavioral parent training and acute stimulant medication treatment on parent-child interactions. Journal of Abnormal Child Psychology. 2014; 42(7):1129–1140 [PubMed: 24687848]

8.: Babinski DE, Waxmonsky JG, Waschbusch DA, Humphrey H, Alfonso A, Crum KI et al. A pilot study of stimulant medication for adults with attention-deficit/hyperactivity disorder (ADHD) who are parents of adolescents with ADHD: the acute effects of stimulant medication on observed parent-adolescent interactions. Journal of Child and Adolescent Psychopharmacology. 2014; 24(10):582–585 [PMC free article: PMC4268552] [PubMed: 25386742]

9.: Dose C, Hautmann C, Buerger M, Schuermann S, Woitecki K, Doepfner M. Telephone-assisted self-help for parents of children with attention-deficit/hyperactivity disorder who have residual functional impairment despite methylphenidate treatment: a randomized controlled trial. Journal of Child Psychology and Psychiatry and Allied Disciplines. 2017; 58(6):682–690 [PubMed: 27878809]

10.: Duric NS, Asmus J, Elgen IB. Self-reported efficacy of neurofeedback treatment in a clinical randomized controlled study of ADHD children and adolescents. Neuropsychiatric Disease and Treatment. 2014; 10:1645–1654 [PMC free article: PMC4159126] [PubMed: 25214789]

11.: Duric NS, Assmus J, Gundersen D, Duric Golos A, Elgen IB. Multimodal treatment in children and adolescents with attention-deficit/hyperactivity disorder: a 6-month follow-up. Nordic Journal of Psychiatry. 2017; Epublication [PubMed: 28345387]

12.: Emilsson B, Gudjonsson G, Sigurdsson JF, Baldursson G, Einarsson E, Olafsdottir H et al. Cognitive behaviour therapy in medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. BMC Psychiatry. 2011; 11:116 [PMC free article: PMC3155481] [PubMed: 21787431]

13.: Estrada RV, Bosch R, Nogueira M, Gomez-Barros N, Valero S, Palomar G et al. Psychoeducation for adults with attention deficit hyperactivity disorder vs. cognitive behavioral group therapy: a randomized controlled pilot study. Journal of Nervous and Mental Disease. 2013; 201(10):894–900 [PubMed: 24080677]

14.: Fabiano GA, Pelham WE, Jr., Gnagy EM, Burrows-MacLean L, Coles EK, Chacko A et al. The single and combined effects of multiple intensities of behavior modification and methylphenidate for children with attention deficit hyperactivity disorder in a classroom setting. School Psychology Review. 2007; 36(2):195–216

15.: Farmer C, Lecavalier L, Yu S, Eugene Arnold L, McDougle CJ, Scahill L et al. Predictors and moderators of parent training efficacy in a sample of children with autism spectrum disorders and serious behavioral problems. Journal of Autism and Developmental Disorders. 2012; 42(6):1037–1044 [PMC free article: PMC3911789] [PubMed: 21822762]

16.: Farmer CA, Brown NV, Gadow KD, Arnold LE, Kolko DG, Findling RL et al. Comorbid symptomatology moderates response to risperidone, stimulant, and parent training in children with severe aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology. 2015; 25(3):213–224 [PMC free article: PMC4403232] [PubMed: 25885011]

17.: Ferrin M, Moreno-Granados JM, Salcedo-Marin MD, Ruiz-Veguilla M, Perez-Ayala V, Taylor E. Evaluation of a psychoeducation programme for parents of children and adolescents with ADHD: immediate and long-term effects using a blind randomized controlled trial. European Child and Adolescent Psychiatry. 2014; 23(8):637–647 [PubMed: 24292412]

18.: Foster EM, Jensen PS, Schlander M, Pelham, Jr., Hechtman L, Arnold LE et al. Treatment for ADHD: Is more complex treatment cost-effective for more complex cases? Health Services Research. 2007; 42(1 I):165–182 [PMC free article: PMC1955245] [PubMed: 17355587]

19.: Gallucci G, Duncan C, Hackerman F. Combination use of atomoxetine and risperidone for hyperactivity and impulsivity in autistic disorder. Mental Health Aspects of Developmental Disabilities. 2006; 9(1):23–25

20.: Gelade K, Janssen TW, Bink M, van Mourik R, Maras A, Oosterlaan J. Behavioral effects of neurofeedback compared to stimulants and physical activity in attention-deficit/hyperactivity disorder: a randomized controlled trial. Journal of Clinical Psychiatry. 2016; 77(10):e1270–e1277 [PubMed: 27631143]

21.: Handen BL, Aman MG, Arnold LE, Hyman SL, Tumuluru RV, Lecavalier L et al. Atomoxetine, parent training, and their combination in children with autism spectrum disorder and attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2015; 54(11):905–915 [PMC free article: PMC4625086] [PubMed: 26506581]

22.: Helseth SA, Waschbusch DA, Gnagy EM, Onyango AN, Burrows-MacLean L, Fabiano GA et al. Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-only, ADHD and conduct problems, and controls. Journal of Consulting and Clinical Psychology. 2015; 83(2):280–292 [PMC free article: PMC4380669] [PubMed: 25495357]

23.: Heriot SA, Evans IM, Foster TM. Critical influences affecting response to various treatments in young children with ADHD: A case series. Child: Care, Health and Development. 2008; 34(1):121–133 [PubMed: 18171453]

24.: Hiscock H, Sciberras E, Mensah F, Gerner B, Efron D, Khano S et al. Impact of a behavioural sleep intervention on symptoms and sleep in children with attention deficit hyperactivity disorder, and parental mental health: randomised controlled trial. BMJ. 2015; 350:h68 [PMC free article: PMC4299655] [PubMed: 25646809]

25.: Jans T, Graf E, Jacob C, Zwanzger U, Gross-Lesch S, Matthies S et al. A randomized controlled multicentre trial on the treatment for ADHD in mothers and children: enrolment and basic characteristics of the study sample. Attention Deficit and Hyperactivity Disorders. 2013; 5(1):29–40 [PubMed: 23070786]

26.: Jans T, Jacob C, Warnke A, Zwanzger U, Gros-Lesch S, Matthies S et al. Does intensive multimodal treatment for maternal ADHD improve the efficacy of parent training for children with ADHD? A randomized controlled multicenter trial. Journal of Child Psychology and Psychiatry and Allied Disciplines. 2015; 56(12):1298–1313 [PubMed: 26123832]

27.: Janssen TWP, Bink M, Geladé K, Mourik R, Maras A, Oosterlaan J. A randomized controlled trial into the effects of neurofeedback, methylphenidate, and physical activity on eeg power spectra in children with adhd. Journal of Child Psychology and Psychiatry. 2016; 57(5):633–644 [PubMed: 26748531]

28.: Jensen PS, Arnold LE, Swanson JM, Vitiello B, Abikoff HB, Greenhill LL et al. 3-Year follow-up of the NIMH MTA study. Journal of the American Academy of Child and Adolescent Psychiatry. 2007; 46(8):989–1002 [PubMed: 17667478]

29.: Jensen PS, Garcia JA, Glied S, Crowe M, Foster M, Schlander M et al. Cost-effectiveness of ADHD treatments: findings from the multimodal treatment study of children with ADHD. American Journal of Psychiatry. 2005; 162(9):1628–1636 [PubMed: 16135621]

30.: Kang KD, Choi JW, Kang SG, Han DH. Sports therapy for attention, cognitions and sociality. International Journal of Sports Medicine. 2011; 32(12):953–959 [PubMed: 22068930]

31.: King S, Griffin S, Hodges Z, Weatherly H, Asseburg C, Richardson G et al. A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents. Health Technology Assessment. 2006; 10(23):iii–iv, xiii–146 [PubMed: 16796929]

32.: Klein RG, Abikoff H. Behavior therapy and methylphenidate in the treatment of children with ADHD. Journal of Attention Disorders. 1997; 2(2):89–114

33.: Konstenius M, Jayaram-Lindstrom N, Beck O, Franck J. Sustained release methylphenidate for the treatment of ADHD in amphetamine abusers: a pilot study. Drug and Alcohol Dependence. 2010; 108(1-2):130–133 [PubMed: 20015599]

34.: Konstenius M, Jayaram-Lindstrom N, Guterstam J, Beck O, Philips B, Franck J. Methylphenidate for ADHD and drug relapse in criminal offenders with substance dependence: A 24-week randomized placebo-controlled trial. Addiction. 2014; 109(3):440–449 [PMC free article: PMC4226329] [PubMed: 24118269]

35.: Konstenius M, Jayaram-Lindstrom N, Guterstam J, Philips B, Beck O, Franck J. Methylphenidate for ADHD in adults with substance dependence: A 24-week randomized placebo-controlled trial. European Psychiatry. 2013; 28:(Suppl 1):1 [PMC free article: PMC4226329] [PubMed: 24118269]

36.: Lee EJ, Jung CH. Additive effects of neurofeedback on the treatment of ADHD: A randomized controlled study. Asian Journal of Psychiatry. 2017; 25:16–21 [PubMed: 28262140]

37.: Levin FR, Evans SM, Brooks DJ, Garawi F. Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. Drug and Alcohol Dependence. 2007; 87(1):20–29 [PubMed: 16930863]

38.: Li L, Yang L, Zhuo CJ, Wang YF. A randomised controlled trial of combined EEG feedback and methylphenidate therapy for the treatment of ADHD. Swiss Medical Weekly. 2013; 143:w13838 [PubMed: 23986461]

39.: Lord J, Paisley S. The clinical effectiveness and cost-effectiveness of methylphenidate for hyperactivity in childhood: Version 2. London. National Institute for Clinical Excellence, 2000.

40.: Meisel V, Servera M, Garcia-Banda G, Cardo E, Moreno I. Neurofeedback and standard pharmacological intervention in ADHD: a randomized controlled trial with six-month follow-up. Biological Psychology. 2013; 94(1):12–21 [PubMed: 23665196]

41.: Merrill BM, Morrow AS, Altszuler AR, Macphee FL, Gnagy EM, Greiner AR et al. Improving homework performance among children with ADHD: a randomized clinical trial. Journal of Consulting and Clinical Psychology. 2017; 85(2):111–122 [PMC free article: PMC5280087] [PubMed: 27618639]

42.: Mesler CF, Holmberg HC, Sperlich B. Multimodal therapy involving high-intensity interval training improves the physical fitness, motor skills, social behavior, and quality of life of boys with ADHD: a randomized controlled study. Journal of Attention Disorders. 2016; Epublication [PubMed: 27013028]

43.: Mohammadi MR, Soleimani AA, Farahmand Z, Keshavarzi S, Ahmadi N. A comparison of effectiveness of regulation of working memory function and methylphenidate on remediation of attention deficit hyperactivity disorder (ADHD). Iranian Journal of Psychiatry. 2014; 9(1):25–30 [PMC free article: PMC4277604] [PubMed: 25561945]

44.: Montoya A, Hervas A, Fuentes J, Cardo E, Polavieja P, Quintero J et al. Cluster-randomized, controlled 12-month trial to evaluate the effect of a parental psychoeducation program on medication persistence in children with attention-deficit/hyperactivity disorder. Neuropsychiatric Disease and Treatment. 2014; 10:1081–1092 [PMC free article: PMC4063801] [PubMed: 24966679]

45.: National Collaborating Centre for Mental Health. Diagnosis and management of ADHD in children, young people and adults. NICE clinical guideline 72. London. Royal College of Psychiatrists and The British Psychological Society, 2008. Available from: http://guidance.nice.org.uk/CG72

46.: National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. London. National Institute for Health and Care Excellence, 2014. Available from: https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869 [PubMed: 26677490]

47.: Pelham WE, Burrows-MacLean L, Gnagy EM, Fabiano GA, Coles EK, Wymbs BT et al. A dose-ranging study of behavioral and pharmacological treatment in social settings for children with ADHD. Journal of Abnormal Child Psychology. 2014; 42(6):1019–1031 [PMC free article: PMC4090274] [PubMed: 24429997]

48.: Pelham WE, Jr., Fabiano GA, Waxmonsky JG, Greiner AR, Gnagy EM, Pelham WE, 3rd et al. Treatment sequencing for childhood ADHD: a multiple-randomization study of adaptive medication and behavioral interventions. Journal of Clinical Child and Adolescent Psychology. 2016; 45(4):396–415 [PMC free article: PMC4930381] [PubMed: 26882332]

49.: Philipsen A, Jans T, Graf E, Matthies S, Borel P, Colla M et al. Effects of group psychotherapy, individual counseling, methylphenidate, and placebo in the treatment of adult attention-deficit/hyperactivity disorder: a randomized clinical trial. JAMA Psychiatry. 2015; 72(12):1199–1210 [PubMed: 26536057]

50.: Riggs PD, Winhusen T, Davies RD, Leimberger JD, Mikulich-Gilbertson S, Klein C et al. Randomized controlled trial of osmotic-release methylphenidate with cognitive-behavioral therapy in adolescents with attention-deficit/hyperactivity disorder and substance use disorders. Journal of the American Academy of Child and Adolescent Psychiatry. 2011; 50(9):903–914 [PMC free article: PMC3164797] [PubMed: 21871372]

51.: Safren SA, Otto MW, Sprich S, Winett CL, Wilens TE, Biederman J. Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms. Behaviour Research and Therapy. 2005; 43(7):831–842 [PubMed: 15896281]

52.: Safren SA, Sprich S, Mimiaga MJ, Surman C, Knouse L, Groves M et al. Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. JAMA. 2010; 304(8):875–880 [PMC free article: PMC3641654] [PubMed: 20736471]

53.: Schachar RJ, Tannock R, Cunningham C, Corkum PV. Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate. Journal of the American Academy of Child and Adolescent Psychiatry. 1997; 36(6):754–763 [PubMed: 9183129]

54.: So CY, Leung PW, Hung SF. Treatment effectiveness of combined medication/behavioural treatment with Chinese ADHD children in routine practice. Behaviour Research and Therapy. 2008; 46(9):983–992 [PubMed: 18692170]

55.: Sprich SE, Safren SA, Finkelstein D, Remmert JE, Hammerness P. A randomized controlled trial of cognitive behavioral therapy for ADHD in medication-treated adolescents. Journal of Child Psychology and Psychiatry and Allied Disciplines. 2016; 57(11):1218–1226 [PMC free article: PMC5026858] [PubMed: 26990084]

56.: Storebo OJ, Gluud C, Winkel P, Simonsen E. Social-skills and parental training plus standard treatment versus standard treatment for children with ADHD--the randomised SOSTRA trial. PloS One. 2012; 7(6):e37280 [PMC free article: PMC3380035] [PubMed: 22745657]

57.: Storebo OJ, Pedersen J, Skoog M, Thomsen PH, Winkel P, Gluud C et al. Randomised social-skills training and parental training plus standard treatment versus standard treatment of children with attention deficit hyperactivity disorder - the SOSTRA trial protocol. Trials. 2011; 12:18 [PMC free article: PMC3038941] [PubMed: 21255399]

58.: Svanborg P, Thernlund G, Gustafsson PA, Hagglof B, Poole L, Kadesjo B. Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in stimulant-naive Swedish children and adolescents. European Child and Adolescent Psychiatry. 2009; 18(4):240–249 [PubMed: 19156355]

59.: Svanborg P, Thernlund G, Gustafsson PA, Hagglof B, Schacht A, Kadesjo B. Atomoxetine improves patient and family coping in attention deficit/hyperactivity disorder: A randomized, double-blind, placebo-controlled study in Swedish children and adolescents. European Child and Adolescent Psychiatry. 2009; 18(12):725–735 [PMC free article: PMC2770135] [PubMed: 19466476]

60.: Tamm L, Adinoff B, Nakonezny PA, Winhusen T, Riggs P. Attention-deficit/hyperactivity disorder subtypes in adolescents with comorbid substance-use disorder. American Journal of Drug and Alcohol Abuse. 2012; 38(1):93–100 [PMC free article: PMC3441182] [PubMed: 21834613]

61.: Thurstone C, Riggs PD, Salomonsen-Sautel S, Mikulich-Gilbertson SK. Randomized, controlled trial of atomoxetine for attention-deficit/hyperactivity disorder in adolescents with substance use disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2010; 49(6):573–582 [PMC free article: PMC2876346] [PubMed: 20494267]

62.: Van der Oord S, Prins PJM, Oosterlaan J, Emmelkamp PMG. Does brief, clinically based, intensive multimodal behavior therapy enhance the effects of methylphenidate in children with ADHD? European Child and Adolescent Psychiatry. 2007; 16(1):48–57 [PubMed: 16972117]

63.: Vidal R, Castells J, Richarte V, Palomar G, Garcia M, Nicolau R et al. Group therapy for adolescents with attention-deficit/hyperactivity disorder: a randomized controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry. 2015; 54(4):275–282 [PubMed: 25791144]

64.: Warden D, Riggs PD, Min SJ, Mikulich-Gilbertson SK, Tamm L, Trello-Rishel K et al. Major depression and treatment response in adolescents with ADHD and substance use disorder. Drug and Alcohol Dependence. 2012; 120(1-3):214–219 [PMC free article: PMC3245790] [PubMed: 21885210]

65.: Waxmonsky JG, Waschbusch DA, Pelham WE, Draganac-Cardona L, Rotella B, Ryan L. Effects of atomoxetine with and without behavior therapy on the school and home functioning of children with attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry. 2010; 71(11):1535–1551 [PubMed: 20673557]

66.: Weiss M, Murray C, Wasdell M, Greenfield B, Giles L, Hechtman L. A randomized controlled trial of CBT therapy for adults with ADHD with and without medication. BMC Psychiatry. 2012; 12:30 [PMC free article: PMC3414742] [PubMed: 22480189]

67.: Young S, Emilsson B, Sigurdsson JF, Khondoker M, Philipp-Wiegmann F, Baldursson G et al. A randomized controlled trial reporting functional outcomes of cognitive-behavioural therapy in medication-treated adults with ADHD and comorbid psychopathology. European Archives of Psychiatry and Clinical Neuroscience. 2017; 267(3):267–276 [PMC free article: PMC5357275] [PubMed: 27752827]

68.: Young S, Khondoker M, Emilsson B, Sigurdsson JF, Philipp-Wiegmann F, Baldursson G et al. Cognitive–behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology: A randomized controlled trial using multi-level analysis. Psychological Medicine. 2015; 45(13):2793–2804 [PMC free article: PMC4595859] [PubMed: 26022103]

69.: Zupancic JAF, Miller A, Raina P. A review of therapies for attention deficit/hyperactivity disorder, Part 3: Economic evaluation of pharmaceutical and psychological/behavioural therapies for attentiondeficit/ hyperactivity disorder. Ottawa. Canadian Coordinating Office for Health Technology Assessment, 1998. Available from: https://www.cadth.ca/media/pdf/adhd_tr_e.pdf

Appendices

Appendix A. Review protocols

Table 44. Review protocol: Combined pharmacological and non-pharmacological treatment

Table 45. Health economic review protocol

Appendix B. Literature search strategies

The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual, Oct 2014, updated 2017. https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869

For more detailed information, please see the Methodology Review.

B.1. Clinical search literature search strategy

Searches for were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and therefore difficult to retrieve. Search filters were applied to the search where appropriate.

Table 46. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

PsycINFO (ProQuest) search terms

B.2. Health Economics literature search strategies

B.2.1. Health economics search strategy

Health economic evidence was identified by conducting a broad search relating to ADHD population in NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA). NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional searches were run on Medline and Embase.

Table 47. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

B.2.2. Quality of Life search strategy

Quality of life evidence was identified by conducting a broad search relating to ADHD population in Medline and Embase.

Table 48. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Appendix C. Clinical evidence selection

Appendix D. Clinical evidence tables

Download PDF (2.1M)

Appendix E. Forest plots

E.1. Children and young people aged 5 to 18

E.1.1. Pharmacological treatment versus non-pharmacological treatment

E.1.2. Combined treatment versus non-pharmacological treatment

E.1.2.1. Atomoxetine + PT/FT versus PT/FT

Figure 52. ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 53. ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 54. ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 55. ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 56. ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 57. ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 58. Responders by CGI-I (PT, <3 months)

E.1.2.2. Atomoxetine + psychoeducation versus psychoeducation

Figure 59. Quality of life (parent rated, total CHIP-CE, unclear range, high is good outcome, CS, PT <3 months)

Figure 60. ADHD symptoms (total, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)

Figure 61. symptoms (hyperactivity, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)

Figure 62. ADHD symptoms (inattention, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)

Figure 63. Academic (parent rated, academic CHIP-CE, unclear range, high is good outcome, CS, PT <3 months)

E.1.2.3. Atomoxetine + CBT versus CBT

Figure 64. ADHD symptoms (total, parent, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months)

Figure 65. ADHD symptoms (total, self, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months)

Figure 66. Responders by CGI-I (PT, <3 months)

E.1.2.4. Stimulants + NF versus NF

Figure 67. ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 68. ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 69. ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 70. ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 71. ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 72. symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 73. ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 74. ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 75. ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 76. ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 77. ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 78. symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 79. ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 80. ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 81. ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 82. ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 83. ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 84. symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 85. Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 86. Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

Figure 87. Academic (general, self, SRQ, 1-10, high is good, PT >3 months)

E.1.2.5. Stimulants + CBT versus CBT

Figure 88. ADHD symptoms (total, observer, ADHD-RS, 0-68, high is poor, FV, PT, >3 months)

E.1.2.6. Mixed medication + PT/FT versus PT/FT

Figure 89. ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 90. ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

Figure 91. ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 92. ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 93. ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 94. ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 95. Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 96. Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 97. Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 98. Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 99. Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

E.1.3. Combined treatment versus pharmacological treatment

E.1.3.1. Atomoxetine + parent/family training versus atomoxetine

Figure 100. ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 101. ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 102. ADHD symptoms (hyperactivity, parent, multiple scales, higher is worse, FV, PT <3 months)

Figure 103. ADHD symptoms (hyperactivity, teacher, multiple scales, higher is worse, FV, PT <3 months)

Figure 104. ADHD symptoms (inattention, parent, multiple scales, higher is worse, FV, PT <3 months)

Figure 105. ADHD symptoms (inattention, teacher, multiple scales, higher is worse, FV, PT <3 months)

Figure 106. Responders by CGI-I (PT, <3 months)

Figure 107. Behaviour/function (behaviour, 0-100, high is good, teacher, PT, <3 months)

E.1.3.2. Stimulants + PT/FT versus stimulants

Figure 108. ADHD symptoms (total, parent, multiple scales, high is poor, FV, PT, >3 months)

Figure 109. ADHD symptoms (total, parent, SWAN, 0-3, high is poor, FV, FU, >3 months)

Figure 110. symptoms (total, teacher, DBDRS, 0-54, high is poor, FV, PT, <3 months)

Figure 111. ADHD symptoms (hyperactivity, parent, multiple scales, 0-3, high is poor, FV, PT, >3 months)

Figure 112. ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 113. ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 114. ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 115. symptoms (inattention, parent, FBB-ADHS, 0-3, high is poor, FV, PT, >3 months)

Figure 116. Behaviour/function (function, parent, WFIRS-P, 0-3, high is poor, FV, PT, >3 months)

E.1.3.3. Stimulants + PT/FT versus stimulants + NSST

Figure 117. ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 118. ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 119. ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 120. symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

E.1.3.4. Stimulants + attention/memory/cognitive training versus stimulants

Figure 121. ADHD symptoms (total, parent, Conners 48, 0-70, high is poor, FV, <3 months PT)

E.1.3.5. Stimulants + NF versus stimulants

Figure 122. ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 123. ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 124. ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 125. ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 126. ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 127. ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 128. ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 129. ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 130. ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 131. ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 132. ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 133. ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 134. ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 135. ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 136. ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 137. ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 138. symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 139. ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 140. Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 141. Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

Figure 142. Academic (general, self, SRQ, 1-10, high is good, PT >3 months)

E.1.3.6. Mixed medication + PT/FT versus mixed medication

Figure 143. ADHD symptoms (total, parent, ADHD-RS-IV,0-54, high is poor, CS, FU, >3 months)

Figure 144. symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 145. ADHD symptoms (hyperactivity, teacher, Conner’s, 0-20, high is poor, FV, PT, <3 months)

Figure 146. ADHD symptoms (hyperactivity, teacher, multiple scales, high is poor, FV, PT, >3 months)

Figure 147. ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 148. ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 149. symptoms (hyperactivity, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

Figure 150. ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 151. ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 152. ADHD symptoms (inattention, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

Figure 153. Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT <3 months)

Figure 154. Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT >3 months)

Figure 155. Emotional dysregulation (CBRS emotional distress subscale, 0-20, high is poor, teacher, PT <3 months)

Figure 156. Emotional dysregulation (CBRS emotional distress subscale, 0-20, high is poor, teacher, PT >3 months)

Figure 157. Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 158. Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 159. Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 160. Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 161. Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

Figure 162. Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT <3 months)

Figure 163. Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT >3 months)

E.1.3.7. Mixed medication + CBT versus mixed medication

Figure 164. ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 165. ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 166. ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 167. ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 168. ADHD symptoms (hyperactivity, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 169. ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 170. ADHD symptoms (inattention, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 171. ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

E.1.3.8. Mixed medication + PE versus mixed medication + NSST

Figure 172. ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

Figure 173. ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

Figure 174. ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

Figure 175. ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

Figure 176. Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

Figure 177. Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

Figure 178. Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, PT <3 months)

Figure 179. Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, FU >3 months)

E.1.3.9. Mixed medication + sleep intervention versus mixed medication

Figure 180. ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 181. ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 182. ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 183. ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 184. ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 185. ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 186. ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 187. ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 188. ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 189. ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 190. ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 191. ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 192. Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, <3 months PT

Figure 193. Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, >3 months PT

E.1.3.10. Mixed medication + NF versus mixed medication

Figure 194. ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT <3 months)

Figure 195. Behaviour/function (CBRS, parent, unclear scale, high is poor, FV, PT <3 months)

E.1.4. Combined treatment versus no treatment/usual care

E.1.4.1. Atomoxetine + PT/FT versus placebo

Figure 196. ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 197. ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 198. ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 199. ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 200. ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 201. ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 202. Responders by CGI-I (PT, <3 months)

E.1.4.2. Mixed medication + PT/FT versus usual care

Figure 203. ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 204. ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

Figure 205. ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 206. ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 207. ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 208. ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 209. Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 210. Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 211. Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 212. Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 213. Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

E.1.5. Combined treatment versus other combined treatment

E.1.5.1. Stimulants + NF versus stimulants + attention/memory/cognitive training

Figure 214. ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 215. ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 216. ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 217. ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 218. ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 219. ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 220. ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 221. ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 222. ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 223. ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 224. ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 225. ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

E.2. Adults over the age of 18

E.2.1. Pharmacological treatment versus non-pharmacological treatment

E.2.1.1. Stimulants + NSST versus CBT alone

Figure 226. ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 227. ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 228. ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 229. ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 230. Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

E.2.2. Combined treatment versus non-pharmacological treatment

E.2.2.1. Stimulants + CBT/DBT versus CBT/DBT alone

Figure 231. ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 232. ADHD symptoms (total, self, multiple tools, decreased by >30%, >3 months PT)

Figure 233. ADHD symptoms (total, observer, TAADDS, decreased by >30%, >3 months PT)

Figure 234. ADHD symptoms (total, observer, multiple tools, high is worse, FV, >3 months PT)

Figure 235. ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 236. symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 237. Emotional dysregulation (multiple tools, 0-15, high is poor, FV, >3 months PT)

Figure 238. Responders by CGI-I (>3 months PT)

Figure 239. Responders by CGI-I (>3 months FU)

E.2.2.2. Stimulants + CBT/DBT + PT/FT versus NSST + PT/FT

Figure 240. ADHD symptoms (total, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

Figure 241. ADHD symptoms (hyperactivity, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

Figure 242. ADHD symptoms (inattention, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

Figure 243. Child’s ADHD symptoms (total, parent, SDQ, 0-10, high is poor, FV, >3 months PT)

Figure 244. Emotional dysregulation (parent, SDQ, 0-10, high is poor, FV, >3 months PT)

E.2.3. Combined treatment versus pharmacological treatment

E.2.3.1. Stimulants + CBT/DBT versus stimulants + NSST

Figure 245. ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 246. symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 247. ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 248. ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 249. Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

E.2.3.2. Mixed medication + CBT/DBT versus mixed medication alone

Figure 250. QoL (Flanagan, 16-112, high is good, FV, <3 months PT)

Figure 251. QoL (Flanagan, 16-112, high is good, FV, <3 months FU)

Figure 252. ADHD symptoms (total, observer, ADHD-RS, 0-54, higher is worse, FV, PT >3 months)

Figure 253. ADHD symptoms (total, self, ADHD-RS, 0-54, higher is worse, FV, PT >3 months)

Figure 254. ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months PT)

Figure 255. ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months FU)

Figure 256. ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months PT)

Figure 257. ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months FU)

Figure 258. symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months PT)

Figure 259. ADHD symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months FU)

Figure 260. Responders by CGI

Figure 261. Emotional dysregulation (HAM-D, observer, 0-53, high is worse, FV, >3 months PT)

Figure 262. Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months PT)

Figure 263. Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months FU)

Figure 264. Behaviour/function (Self-rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months PT)

Figure 265. Behaviour/function (Self-rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months FU)

E.2.3.3. Mixed medication + CBT/DBT versus mixed medication + NSST

Figure 266. QoL (QLESQ, unclear scale, high is better, FV, >3 months PT)

Figure 267. ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months PT)

Figure 268. ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months FU)

Figure 269. ADHD symptoms (hyperactivity, self, CAARS, high is worse, FV, 0-27, >3 months PT)

Figure 270. ADHD symptoms (inattention, self, CAARS, high is worse, FV, 0-27, >3 months PT)

Figure 271. CGI-I responders (>3 months PT)

Figure 272. Emotional dysregulation (Self, BDI, 0-63, high is worse, FV, >3 months PT)

E.2.4. Combined treatment versus no treatment/usual care

E.2.4.1. Stimulants + CBT/DBT versus NSST alone

Figure 273. ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 274. ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 275. ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 276. ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 277. Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

Appendix F. GRADE tables

Children and young people (5-18 years old)

DRUGS versus NON-DRUGS

Table 49. Clinical evidence profile: Atomoxetine versus Parent/Family training for ADHD in children and young people

Table 50. Clinical evidence profile: Stimulants versus exercise for ADHD in children and young people

Table 51. Clinical evidence profile: Stimulants versus Neurofeedback for ADHD in children and young people

Table 52. Clinical evidence profile: Stimulants + NSST versus stimulants for ADHD in children and young people

Table 53. Clinical evidence profile: Mixed medication versus PT/FT for ADHD in children and young people

COMBINATION versus NON-DRUGS

Table 54. Clinical evidence profile: Atomoxetine + PT/FT versus PT/FT for ADHD in children and young people

Table 55. Clinical evidence profile: Atomoxetine + PE versus PE for ADHD in children and young people

Table 56. Clinical evidence profile: Atomoxetine + CBT versus CBT for ADHD in children and young people

Table 57. Clinical evidence profile: Stimulants + NF versus NF for ADHD in children and young people

Table 58. Clinical evidence profile: Stimulants + CBT versus CBT for ADHD in children and young people

Table 59. Clinical evidence profile: Mixed medication + PT/FT versus PT/FT for ADHD in children and young people

COMBINATION versus DRUGS

Table 60. Clinical evidence profile: Atomoxetine + PT/FT versus atomoxetine for ADHD in children and young people

Table 61. Clinical evidence profile: Stimulants + PT/FT versus stimulants for ADHD in children and young people

Table 62. Clinical evidence profile: Stimulants + PT/FT versus stimulants + NSST for ADHD in children and young people

Table 63. Clinical evidence profile: Stimulants + attention/memory/cognitive training versus stimulants for ADHD in children and young people

Table 64. Clinical evidence profile: Stimulants + NF versus stimulants for ADHD in children and young people

Table 65. Clinical evidence profile: Mixed medication + PT/FT versus mixed medication for ADHD in children and young people

Table 66. Clinical evidence profile: Mixed medication + CBT versus mixed medication for ADHD in children and young people

Table 67. Clinical evidence profile: Mixed medication + PE versus mixed medication + NSST for ADHD in children and young people

Table 68. Clinical evidence profile: Mixed medication + sleep intervention versus mixed medication for ADHD in children and young people

Table 69. Clinical evidence profile: Mixed medication + NF versus mixed medication for ADHD in children and young people

COMBINATION versus NOTHING

Table 70. Clinical evidence profile: Atomoxetine + PT/FT versus placebo/usual care for ADHD in children and young people

Table 71. Clinical evidence profile: Mixed medication + PT/FT versus placebo/usual care for ADHD in children and young people

COMBINATION versus OTHER COMBINATION

Table 72. Clinical evidence profile: Stimulants + NF versus stimulants + attention/memory/cognitive training for ADHD in children and young people

Adults (>18 years old)

DRUGS versus NON-DRUGS

Table 73. Clinical evidence profile: Stimulants +NSST versus CBT for ADHD in adults

COMBINATION versus NON-DRUGS

Table 74. Clinical evidence profile: Stimulants + CBT/DBT versus CBT/DBT for ADHD in adults

Table 75. Clinical evidence profile: Stimulants + CBT/DBT + PT/FT versus NSST + PT/FT for ADHD in adults

COMBINATION versus DRUGS

Table 76. Clinical evidence profile: Stimulants + CBT/DBT versus stimulants + NSST for ADHD in adults

Table 77. Clinical evidence profile: Medication + CBT/DBT versus medication for ADHD in adults

Table 78. Clinical evidence profile: Medication + CBT/DBT versus Medication + NSST for ADHD in adults

COMBINATION versus NOTHING/USUAL CARE

Table 79. Clinical evidence profile: Stimulants + CBT/DBT versus NSST for ADHD in adults

Appendix G. Health economic evidence selection

* Non-relevant population, intervention, comparison, design or setting; non-English language

Appendix H. Health economic evidence tables

None.

Appendix I. Excluded studies

I.1. Excluded clinical studies

Table 80. Studies excluded from the clinical review

I.2. Excluded health economic studies

Table 81. Studies excluded from the health economic review

Appendix J. Research recommendations

J.1. Combination in children under 5

Research question: What is the clinical and cost effectiveness of pharmacological vs non-pharmacological treatment versus a combination in children under 5 with ADHD?

Why this is important:

Many children are diagnosed with ADHD under the age of 5 years. There is much hesitancy around the use of ADHD medication in this age group, although there has been little research into the option. There is more evidence in this age group supporting the efficacy of non-pharmacological interventions (for example parent- training programmes), but there is no evidence directly comparing the efficacy of this with pharmacological treatment or a combination of the two.

Criteria for selecting high-priority research recommendations

J.2. Combination in over 5s

Research question: What is the clinical and cost effectiveness of pharmacological vs non-pharmacological treatment versus a combination in children, young people and adults over 5 with ADHD?

Why this is important:

The question of the direct head to head comparisons between pharmacological and non-pharmacological treatment or a combination of the two in children, young people and adults over 5 with ADHD is critical to treatment decisions. There are many small studies looking at a variety of specific interventions under this heading but a paucity of large, well conducted RCTs of the kind that would be required for stronger recommendations and more useful information for patients.

Criteria for selecting high-priority research recommendations

Final

Intervention evidence review

These evidence reviews were developed by the National Guideline Centre

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.

Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Bookshelf ID: NBK578099PMID: 35192260

Table 1PICO characteristics of review question

Population	Children, young people and adults with ADHD. Stratified by age: Under 5 years 5 to 18 years Over 18 years
Intervention(s)	Pharmacological treatments (mixed, stimulants [including methylphenidate, dexamfetamine and lisdexamfetamine], atomoxetine, guanfacine) Non-pharmacological treatments (parent/family/carer training, cognitive behavioural therapy (CBT), Dialectical behaviour therapy (DBT), psychoeducation, attention/memory/cognitive training, neurofeedback, relaxation techniques, organisational skills/school or workplace targeted interventions, exercise, outdoor activities, non-specific supportive therapy (NSST)) Combinations of pharmacological and non-pharmacological treatments
Comparison(s)	Any pharmacological treatment versus any non-pharmacological treatment Any combined treatment versus any pharmacological/non-pharmacological treatment alone Any combined treatment versus any other combined treatment Any combined treatment versus usual care
Outcomes	Quality of life ADHD symptoms (total, inattention, hyperactivity, stratified by rater) Discontinuation due to intervention Serious adverse events Behavioural measures Emotional dysregulation Academic outcomes
Study design	RCTs only

Table 2Summary of studies included in the evidence review for children aged over 5 to 18

Study	Intervention and comparison	Population	Outcomes	Comments
Abikoff 2004³	Stimulants alone (n = 34), 12 months Stimulants + parent/family training (n = 34), 12 months Stimulants + nonspecific supportive therapy (n = 35), 12 months Follow-up to 2 years	Aged 7 to 9.9 (mean 8.2) Participants were all selected as responders to 5 weeks of open label methylphenidate USA	ADHD symptoms	General ADHD population
Dose 2016⁹	Stimulants + parent/family training (n = 51) Stimulants (n = 52) Follow-up and intervention duration 12 months	Aged 6 to 12 Participants were previously using drugs for ADHD and not responding Germany	ADHD symptoms Behaviour/function	General ADHD population Parent/family training predominantly delivered via mailed self-help manuals with telephone follow-up
Duric 2014¹⁰	Stimulants + neurofeedback (n = 22) Stimulants (n = 27) Neurofeedback (n = 24) Follow-up (estimated intervention duration) 10 weeks	Aged 6 to 17 (mean 11.5) Not selected based on previous treatment or response Norway	ADHD symptoms Academic	General ADHD population
Duric 2017¹¹	Stimulants + neurofeedback (n=44), 3 months Stimulants (n=42), 3 months Neurofeedback (n=42), 3 months Follow-up 6 months	Aged 6 to 18 (mean 11.2) Not selected based on previous treatment or response Norway	ADHD symptoms Academic	General ADHD population
Ferrin 2014¹⁷	Mixed medication + psychoeducation (n = 40), 12 weeks Mixed medication + non-specific supportive therapy (n = 36), 12 weeks Follow-up to 15 months	Aged 3 to 19 (mean 10.65) Not selected based on previous treatment or response Spain	ADHD symptoms Behaviour/function Emotional dysregulation	General ADHD population
Gelade 2016²⁰	Stimulants (n = 33) Exercise (n = 37) Follow-up and intervention duration to 10-12 weeks	Mean age 9.63 (SD 1.76) All were free of stimulant use for at least 1 month Netherlands	ADHD symptoms	General ADHD population
Handen 2015²¹	Atomoxetine + parent/family training (n = 32) Atomoxetine (n = 32) Parent/family training (n = 32) Placebo/usual care (n = 32) Follow-up and intervention duration 10 weeks	Aged 5 to 14 (mean age 8.1) USA	ADHD symptoms Responders by CGI-I	ADHD and ASD
Hiscock 2015²⁴	Mixed medication + sleep intervention (n = 122) Mixed medication (n = 122) Follow-up and intervention duration 6 months	Aged 5 to 12 years Not selected based on previous treatment or response Australia	ADHD symptoms Behaviour/function	General ADHD population
Lee 2017³⁶	Mixed medication + neurofeedback (n = 18) Mixed medication (n = 18) Follow-up and intervention duration 10 weeks	Mean age 8.7 (SD 2) Not selected based on previous treatment or response South Korea	ADHD symptoms Behaviour/function	General ADHD population
Li 2013³⁸	Stimulants + neurofeedback (n = 31), 8-20 weeks Stimulants + attention training (n = 29), 8-20 weeks Follow-up to 6 months	Mean age 10.6 (SD 2.8) Not selected based on previous treatment or response China	ADHD symptoms	General ADHD population
MTA study 1999¹^,²⁸	Mixed medication + parent/family training (n = 134), 14 months Mixed medication (n = 120), 14 months Parent/family training (n = 129), 14 months Waitlist/usual care (n = 128) Follow-up to 3 years	Mean age 8.5 (SD 0.8) Not selected based on previous treatment or response USA	ADHD symptoms Academic	General ADHD population
Merrill 2016⁴¹	Mixed medication + parent/family training (n = 39) Parent/family training (n = 36) Mixed medication (n = 36) Waitlist/usual care (n = 36) Follow-up and intervention duration 2 months	Mean age 8 (SD 1.7) Not selected based on previous treatment or response USA	Academic	General ADHD population
Mohammadi 2014⁴³	Stimulants + attention/memory/cognitive training (n = 23) Stimulants (n = 25) Follow-up to ~2 months	Age range from 6 to 12 Not selected based on previous treatment or response Iran	ADHD symptoms	General ADHD population
Montoya 2014⁴⁴	Mixed medication + parent/family training (n = 144) Mixed medication (n = 126) Follow-up to 12 months (intervention duration unclear)	Mean age 9.1 (SD 1.9) Participants were pharmacologically naïve Spain	ADHD symptoms	General ADHD population
Riggs 2011⁵⁰	Stimulants + CBT (n = 151) CBT (n = 152) Follow-up and intervention duration 4 months	Mean age 16.5 (SD 1.3) Participants had not used psychotropic medication in previous month USA	ADHD symptoms	Majority moderate severity Comorbid non-tobacco substance use disorder
So 2008⁵⁴	Stimulants + parent/family training (n = 45) Stimulants (n = 31) Follow-up to 18 months	Mean age 8.0 (SD 0.9) Participants were pharmacologically naïve Hong Kong	ADHD symptoms	General ADHD population
Sprich 2016⁵⁵	Mixed medication + CBT (n = 46), 6 months Mixed medication (n = 46), 6 months Follow-up to 1 month	Mean age 15.13 (SD 1.1) Participants were previously using drugs for ADHD and not responding USA	ADHD symptoms	General ADHD population
Storebo 2012⁵⁶	Mixed medication + parent/family training (n = 28) Mixed medication (n = 27) Follow-up and intervention duration 6 months	Age range 8 to 12 Participants were pharmacologically naïve Denmark	ADHD symptoms Behaviour/function Emotional dysregulation Academic	General ADHD population
Svanborg 2009⁵⁹	Atomoxetine + psychoeducation (n = 49) Psychoeducation (n = 50) Follow-up and intervention duration 10 weeks	Age range 6 to 15 Participants were pharmacologically naïve Sweden	Quality of life ADHD symptoms Academic	General ADHD population
Thurstone 2010⁶¹	Atomoxetine + CBT (n = 32) CBT (n = 33) Follow-up and intervention duration 3 months	Mean age 16.1 (SD 1.6) Not selected based on previous treatment or response USA	ADHD symptoms Responders by CGI-I	Comorbid non-tobacco substance use disorder
Van der Oord⁶²	Stimulants + parent/family training (n = 24) Stimulants (n = 21) Follow-up and intervention duration 10 weeks	Mean age 9.9 (SD 1.2) Participants were pharmacologically naïve Netherlands	ADHD symptoms	General ADHD population
Vidal 2015⁶³	Mixed medication + CBT (n = 59) Mixed medication (n = 60) Follow-up and intervention duration to ~3 months	Mean age 17.47 (SD 1.88) Participants were previously treated with ADHD medication, response not specified Spain	ADHD symptoms	General ADHD population
Waxmonsky 2010⁶⁵	Atomoxetine + parent/family training (n = 29) Atomoxetine (n = 27) Follow-up and intervention duration 2 months	Mean age 8.59 (SD 1.58) Not selected based on previous treatment or response USA	ADHD symptoms Responders by CGI-I Behaviour/function	General ADHD population

Table 3Summary of studies included in the evidence review for adults

Study

Intervention and comparison

Population

Outcomes

Comments

Emilsson 2011¹²

Mixed medication + CBT (n = 15), 8 weeks

Mixed medication (n = 17), 8 weeks

Follow-up to ~5 months

Mean age 33.88 (SD 11.47)

Participants were previously treated with ADHD medication, with persistent symptoms

Iceland

ADHD symptoms

General ADHD population

Estrada 2013¹³

Mixed medication + CBT (n = 15)

Mixed medication + non-specific supportive therapy (n = 17)

Follow-up and intervention duration 3 months

Mean age 39.47 (SD 7.68)

Participants were previously treated with ADHD medication, partially responsive

Spain

Quality of life

ADHD symptoms

Emotional dysregulation

General ADHD population

Jans 2015²⁶

Stimulants + CBT + parent/family training (n = 77)

Non-specific supportive therapy + parent/family training (n = 66)

Follow-up and intervention duration 1 year

Mean age 38.32 (SD 5.69)

Participants were not previously treated with methylphenidate or psychotherapy

Germany

ADHD symptoms (maternal)

ADHD symptoms (child)

Emotional dysregulation

Mothers with ADHD, with children with ADHD (treatment aimed at mothers)

Both groups received parent/family training after a period of either stimulant and CBT treatment or non-specific supportive treatment

Konstenius 2014³⁴

Stimulants + CBT (n = 27)

CBT (n = 26)

Follow-up and intervention duration 6 months

Mean age 41.5 (SD 9.83)

Not selected based on previous treatment or response

Sweden

ADHD symptoms

Participants from medium security prisons with comorbid amphetamine dependence

Levin 2007³⁷

Stimulants + CBT (n = 53)

CBT (n = 53)

Follow-up and intervention duration 14 weeks

Mean age 37 (SD 6.5)

Not selected based on previous treatment or response

USA

ADHD symptoms

Responders by CGI-I

Comorbid cocaine dependence

Philipsen 2015⁴⁹

Stimulants + CBT (n = 103)

Stimulants + non-specific supportive therapy (n = 110)

Placebo + CBT (n = 107)

Placebo + non-specific supportive therapy (n = 103)

Follow-up and intervention duration 1 year

Mean age 35 (SD 10.26)

Participants had not used stimulants for ADHD or psychotherapy aimed at ADHD in preceding 6 months

Germany

ADHD symptoms

Emotional dysregulation

General ADHD population

Safren 2005⁵¹

Mixed medication + CBT (n = 16)

Mixed medication (n = 15)

Follow-up and intervention duration 15 weeks

Mean age 45.5 (SD 10.6)

Participants were previously using ADHD medication and responsive but with persistent symptoms

USA

ADHD symptoms

Emotional dysregulation

General ADHD population

Safren 2010⁵²

Mixed medication + CBT (n = 38), 15 weeks

Mixed medication + non-specific supportive therapy (n = 32), 15 weeks

Follow-up to ~18 months

Mean age 43.2 (SD 11.3)

Participants were previously using medication for ADHD and had persistent symptoms

USA

ADHD symptoms

CGI-I responders

General ADHD population

Weiss 2012⁶⁶

Stimulants + CBT (n = 23), 14 weeks

CBT (n = 25)

Follow-up to 5 months, 14 weeks

Mean age 35.6 (SD 9.9)

Not selected based on previous treatment or response

USA and Canada

ADHD symptoms

Responders by CGI-I

Emotional dysregulation

General ADHD population

Young 2015⁶⁷^,⁶⁸

Mixed medication + CBT (n = 25)

Mixed medication (n = 32)

Follow-up and intervention duration 3 months

Mean age 35.2 (SD 11.7)

Previously on medication for ADHD, response not specified

Iceland

Quality of life

ADHD symptoms

Emotional dysregulation Behaviour/function

General ADHD population

Table 4Clinical evidence summary: Atomoxetine versus parent/family training

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with PT/FT

Risk difference with Atomoxetine (95% CI)

ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.45

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.21 lower

(0.5 lower to 0.08 higher)

ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.46

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.03 higher

(0.35 lower to 0.41 higher)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.44

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.32 lower

(0.68 lower to 0.04 higher)

ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.28

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.04 higher

(0.43 lower to 0.51 higher)

ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.45

The mean ADHD symptoms (inattention, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.09 lower

(0.41 lower to 0.23 higher)

ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.64

The mean ADHD symptoms (inattention, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.02 higher

(0.37 lower to 0.41 higher)

Responders by CGI-I (PT, <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

RR 1.61

(0.83 to 3.13)

290 per 1000

177 more per 1000

(from 49 fewer to 618 more)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

Table 5Clinical evidence summary: Stimulants versus exercise

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Exercise

Risk difference with Stimulants (95% CI)

ADHD symptoms (hyperactivity, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, swan, high is poor, fv, pt <3 months) in the control groups was

1.07

The mean ADHD symptoms (hyperactivity, parent, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.45 lower

(0.84 to 0.06 lower)

ADHD symptoms (hyperactivity, teacher, SWAN,0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, swan, high is poor, fv, pt <3 months) in the control groups was

1.1

The mean ADHD symptoms (hyperactivity, teacher, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.87 lower

(1.3 to 0.44 lower)

ADHD symptoms (inattention, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, swan, high is poor, fv, pt <3 months) in the control groups was

1.11

The mean ADHD symptoms (inattention, parent, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.50 lower

(0.86 to 0.14 lower)

ADHD symptoms (inattention, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

MODERATE^a

due to risk of bias

The mean ADHD symptoms (inattention, teacher, swan, high is poor, fv, pt <3 months) in the control groups was

1.33

The mean ADHD symptoms (inattention, teacher, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.76 lower

(1.12 to 0.4 lower)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

Table 6Clinical evidence summary: Stimulants versus Neurofeedback

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with NF

Risk difference with Stimulants (95% CI)

ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

23.5

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

4.60 higher

(0.46 to 8.74 higher)

ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

23.8

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.30 lower

(5.21 lower to 4.61 higher)

ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.70 higher

(2.93 lower to 8.33 higher)

ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

25.3

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.80 higher

(4.45 lower to 6.05 higher)

ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

9.2

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

3.00 higher

(0.49 to 5.51 higher)

ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

1.40 higher

(1.43 lower to 4.23 higher)

ADHD symptoms (hyperactivity, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^b^,^d

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, swan, high is poor, fv, pt <3 months) in the control groups was

1.02

The mean ADHD symptoms (hyperactivity, parent, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.40 lower

(0.79 to 0.01 lower)

ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

10.8

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

0.40 higher

(3.33 lower to 4.13 higher)

ADHD symptoms (hyperactivity, teacher, Barkley’s,0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

10.5

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

2.50 higher

(0.59 lower to 5.59 higher)

ADHD symptoms (hyperactivity, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^b^,^d

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, swan, high is poor, fv, pt <3 months) in the control groups was

1.16

The mean ADHD symptoms (hyperactivity, teacher, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.93 lower

(1.39 to 0.47 lower)

ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self, srq, 1-10, high is good, cs, pt <3 months) in the control groups was

1.4

The mean ADHD symptoms (hyperactivity, self, srq, 1-10, high is good, cs, pt <3 months) in the intervention groups was

0.10 lower

(1.63 lower to 1.43 higher)

ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, <3 months) in the control groups was

5.8

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, <3 months) in the intervention groups was

0.60 higher

(0.90 lower to 2.10 higher)

ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, >3 months) in the control groups was

5.8

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, >3 months) in the intervention groups was

0.10 higher

(1.18 lower to 1.38 higher)

ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

14.3

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

1.60 higher

(0.91 lower to 4.11 higher)

ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

13.9

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

1.80 lower

(4.42 lower to 0.82 higher)

ADHD symptoms (inattention, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^b^,^d

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, swan, high is poor, fv, pt <3 months) in the control groups was

1.11

The mean ADHD symptoms (inattention, parent, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.50 lower

(0.84 to 0.16 lower)

ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

10.2

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.30 higher

(0.55 lower to 5.15 higher)

ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

14.8

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

1.70 lower

(4.53 lower to 1.13 higher)

ADHD symptoms (inattention, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

(1 study)

10-12 weeks

LOW^b^,^d

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, swan, high is poor, fv, pt <3 months) in the control groups was

1.3

The mean ADHD symptoms (inattention, teacher, swan, high is poor, fv, pt <3 months) in the intervention groups was

0.73 lower

(1.09 to 0.37 lower)

ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, <3 months) in the control groups was

6.5

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, <3 months) in the intervention groups was

0.20 higher

(1.02 lower to 1.42 higher)

ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, >3 months) in the control groups was

5.6

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, >3 months) in the intervention groups was

0.40 higher

(0.68 lower to 1.48 higher)

ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self, srq, 1-10, high is good, cs, pt <3 months) in the control groups was

1.8

The mean ADHD symptoms (inattention, self, srq, 1-10, high is good, cs, pt <3 months) in the intervention groups was

0.40 lower

(1.75 lower to 0.95 higher)

Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, cs, pt <3 months) in the control groups was

1.5

The mean academic (general, self, 1-10, high is good, cs, pt <3 months) in the intervention groups was

1.40 lower

(3.22 lower to 0.42 higher)

Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, pt <3 months) in the control groups was

5.8

The mean academic (general, self, 1-10, high is good, pt <3 months) in the intervention groups was

0.60 higher

(0.90 lower to 2.10 higher)

Academic (general, self, SRQ, 1-10, high is good, FU >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, pt >3 months) in the control groups was

5.8

The mean academic (general, self, 1-10, high is good, pt >3 months) in the intervention groups was

0.10 higher

(1.18 lower to 1.38 higher)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

(c): Downgraded by 2 increments if the confidence interval crossed both MIDs.

(d): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

Table 7Clinical evidence summary: Stimulants + non-specific supportive therapy versus stimulants

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Stimulants

Risk difference with Stimulants + NSST (95% CI)

ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, pt >3 months) in the control groups was

1.1

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, pt >3 months) in the intervention groups was

0.10 lower

(0.38 lower to 0.18 higher)

ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, fu >3 months) in the control groups was

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, fu >3 months) in the intervention groups was

0.20 lower

(0.44 lower to 0.04 higher)

ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, pt >3 months) in the control groups was

1.2

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, pt >3 months) in the intervention groups was

0.30 lower

(0.68 lower to 0.08 higher)

ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, fu >3 months) in the control groups was

1.1

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, fu >3 months) in the intervention groups was

0.40 lower

(0.7 to 0.1 lower)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

Table 8Clinical evidence summary: Mixed medication versus parent/family training

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with parent/family training

Risk difference with Mixed medication (95% CI)

ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

242

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean ADHD symptoms (total, teacher and parent, snap, 0-3, high is poor, fv, fu >3 months) in the control groups was

1.27

The mean ADHD symptoms (total, teacher and parent, snap, 0-3, high is poor, fv, fu >3 months) in the intervention groups was

0.06 lower

(0.21 lower to 0.09 higher)

ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

239

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, high is poor, fv, pt, >3 months) in the control groups was

1.1

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, high is poor, fv, pt, >3 months) in the intervention groups was

0.28 lower

(0.47 to 0.09 lower)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

250

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, high is poor, fv, pt >3 months) in the control groups was

1.24

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, high is poor, fv, pt >3 months) in the intervention groups was

0.33 lower

(0.5 to 0.16 lower)

ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

217

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, snap, 0-3, high is poor, fv, pt >3 months) in the control groups was

0.29

The mean ADHD symptoms (hyperactivity, observer, snap, 0-3,high is poor, fv, pt >3 months) in the intervention groups was

0.13 lower

(0.19 to 0.07 lower)

ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

250

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, snap, 0-3, high is poor, fv, pt >3 months) in the control groups was

1.4

The mean ADHD symptoms (inattention, parent, snap, 0-3, high is poor, fv, pt >3 months) in the intervention groups was

0.28 lower

(0.45 to 0.11 lower)

ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

240

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, snap, 0-3, high is poor, fv, pt >3 months) in the control groups was

1.47

The mean ADHD symptoms (inattention, teacher, snap, 0-3, high is poor, fv, pt >3 months) in the intervention groups was

0.36 lower

(0.56 to 0.16 lower)

Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean academic outcomes (maths accuracy %, observer, high is better, pt <3 months) in the control groups was

91.9

The mean academic outcomes (maths accuracy %, observer, high is better, pt <3 months) in the intervention groups was

4.14 lower

(7.04 to 1.24 lower)

Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

258

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

100.3

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the intervention groups was

0.60 lower

(3.86 lower to 2.66 higher)

Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean academic outcomes (reading accuracy %, observer, high is better, pt <3 months) in the control groups was

91.59

The mean academic outcomes (reading accuracy %, observer,high is better, pt <3 months) in the intervention groups was

5.45 lower

(9.36 to 1.54 lower)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

258

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

96.2

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the intervention groups was

1.70 higher

(1.84 lower to 5.24 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

242

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, fu >3 months) in the control groups was

98.3

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, fu >3 months) in the intervention groups was

0.50 lower

(3.98 lower to 2.98 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

(c): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 9Clinical evidence summary: Atomoxetine + parent/family training versus parent/family training

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with parent/family training

Risk difference with Atomoxetine + PT/FT (95% CI)

ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.45

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.22 lower

(0.54 lower to 0.1 higher)

ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms

(total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.46

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.32 lower

(0.72 lower to 0.08 higher)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.44

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.29 lower

(0.65 lower to 0.07 higher)

ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.28

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.30 lower

(0.77 lower to 0.17 higher)

ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.45

The mean ADHD symptoms (inattention, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.15 lower

(0.5 lower to 0.2 higher)

ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.64

The mean ADHD symptoms (inattention, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.34 lower

(0.75 lower to 0.07 higher)

Responders by CGI-I (PT, <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

RR 1.67

(0.86 to 3.22)

290 per 1000

194 more per 1000

(from 41 fewer to 644 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

Table 10Clinical evidence summary: Atomoxetine + PE versus PE

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with PE	Risk difference with Atomoxetine + PE (95% CI)
Quality of life (parent rated, total CHIP-CE, unclear range, high is good outcome, CS, PT <3 months)	99 (1 study) 10 weeks	MODERATE^a due to imprecision		The mean quality of life (parent rated, total chip-ce, unclear range, high is good outcome, cs, pt <3 months) in the control groups was 5.2	The mean quality of life (parent rated, total chip-ce, unclear range, high is good outcome, cs, pt <3 months) in the intervention groups was 1.40 higher (1.93 lower to 4.73 higher)
ADHD symptoms (total, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)	99 (1 study) 10 weeks	HIGH		The mean ADHD symptoms (total, parent, ADHD-rs, high is poor, cs, pt, <3 months) in the control groups was −6.3	The mean ADHD symptoms (total, parent, ADHD-rs, high is poor, cs, pt, <3 months) in the intervention groups was 12.70 lower (16.86 to 8.54 lower)
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)	99 (1 study) 10 weeks	HIGH		The mean ADHD symptoms (hyperactivity, parent, ADHD-rs, high is poor, cs, pt, <3 months) in the control groups was −2.5	The mean ADHD symptoms (hyperactivity, parent, ADHD-rs, high is poor, cs, pt, <3 months) in the intervention groups was 6.20 lower (8.42 to 3.98 lower)
ADHD symptoms (inattention, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)	99 (1 study) 10 weeks	HIGH		The mean ADHD symptoms (inattention, parent, ADHD-rs, high is poor, cs, pt, <3 months) in the control groups was −3.8	The mean ADHD symptoms (inattention, parent, ADHD-rs, high is poor, cs, pt, <3 months) in the intervention groups was 6.50 lower (8.5 to 4.5 lower)
Academic (parent rated, academic CHIP-CE, unclear range, high is good outcome, CS, PT <3 months)	99 (1 study) 10 weeks	MODERATE^a due to imprecision		The mean academic (parent rated, academic chip-ce, unclear range, high is good outcome, cs, pt <3 months) in the control groups was 2.4	The mean academic (parent rated, academic chip-ce, unclear range, high is good outcome, cs, pt <3 months) in the intervention groups was 4.30 higher (0.83 to 7.77 higher)

(a): Downgraded by 1 increment if the confidence interval crossed 1 MID.

Table 11Clinical evidence summary: Atomoxetine + CBT versus CBT

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with CBT	Risk difference with Atomoxetine + CBT (95% CI)
ADHD symptoms (total, parent, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months)	65 (1 study) 12 weeks	LOW^a^,^b due to risk of bias, imprecision		The mean ADHD symptoms (total, parent, dsm-iv checklist, 0-54, high is poor, cs, pt <3 months) in the control groups was 8.82	The mean ADHD symptoms (total, parent, dsm-iv checklist, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 5.00 higher (1.87 lower to 11.87 higher)
ADHD symptoms (total, self, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months)	65 (1 study) 12 weeks	LOW^a^,^b due to risk of bias, imprecision		The mean ADHD symptoms (total, self, dsm-iv checklist, 0-54, high is poor, cs, pt <3 months) in the control groups was 19.02	The mean ADHD symptoms (total, self, dsm-iv checklist, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.83 lower (7.52 lower to 5.86 higher)
Responders by CGI-I (PT, <3 months)	65 (1 study) 12 weeks	VERY LOW^a^,^c due to risk of bias, imprecision	RR 0.88 (0.57 to 1.34)	Moderate
Responders by CGI-I (PT, <3 months)	65 (1 study) 12 weeks	VERY LOW^a^,^c due to risk of bias, imprecision	RR 0.88 (0.57 to 1.34)	606 per 1000	73 fewer per 1000 (from 261 fewer to 206 more)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

(c): Downgraded by 2 increments if the confidence interval crossed both MIDs.

Table 12Clinical evidence summary: Stimulants + NF versus NF

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with NF

Risk difference with Stimulants + NF (95% CI)

ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

23.5

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

1.10 higher

(3.03 lower to 5.23 higher)

ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

23.8

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

1.10 lower

(6.01 lower to 3.81 higher)

ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, <3 months) in the

control groups was

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

0.10 higher

(5.87 lower to 6.07 higher)

ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

25.3

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

3.20 lower

(8.73 lower to 2.33 higher)

ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

9.2

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

0.30 higher

(2.21 lower to 2.81 higher)

ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.90 higher

(2.00 lower to 3.80 higher)

ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

10.8

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.10 lower

(6.03 lower to 1.83 higher)

ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

10.5

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.00 higher

(3.24 lower to 3.24 higher)

ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, <3 months) in the control groups was

5.8

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, <3 months) in the intervention groups was

1.20 higher

(0.36 lower to 2.76 higher)

ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, FU, >3 months)

(1 study)

6 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, >3 months) in the control groups was

5.8

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, >3 months) in the intervention groups was

0.10 higher

(1.18 lower to 1.38 higher)

ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self, srq, 1-10, high is good, cs, pt <3 months) in the control groups was

1.4

The mean ADHD symptoms (hyperactivity, self, srq, 1-10, high is good, cs, pt <3 months) in the intervention groups was

0.40 lower

(2 lower to 1.2 higher)

ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

14.3

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

0.80 higher

(1.71 lower to 3.31 higher)

ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

13.9

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

2.10 lower

(4.79 lower to 0.59 higher)

ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

10.2

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.20 higher

(0.78 lower to 5.18 higher)

ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

14.8

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

3.20 lower

(6.17 to 0.23 lower)

ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, <3 months) in the control groups was

6.5

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, <3 months) in the intervention groups was

0.20 lower

(1.42 lower to 1.02 higher)

ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, >3 months) in the control groups was

5.6

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, >3 months) in the intervention groups was

1.30 higher

(0.22 to 2.38 higher)

ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self, srq, 1-10, high is good, cs, pt <3 months) in the control groups was

1.8

The mean ADHD symptoms (inattention, self, srq, 1-10, high is good, cs, pt <3 months) in the intervention groups was

0.60 lower

(1.88 lower to 0.68 higher)

Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, cs, pt <3 months) in the control groups was

1.5

The mean academic (general, self, 1-10, high is good, cs, pt <3 months) in the intervention groups was

2.50 lower

(4.31 to 0.69 lower)

Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, pt <3 months) in the control groups was

5.8

The mean academic (general, self, 1-10, high is good, pt <3 months) in the intervention groups was

1.20 higher

(0.36 lower to 2.76 higher)

Academic (general, self, SRQ, 1-10, high is good, FU >3 months)

(1 study)

6 months

LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, pt >3 months) in the control groups was

5.8

The mean academic (general, self, 1-10, high is good, pt >3 months) in the intervention groups was

0.10 higher

(1.18 lower to 1.38 higher)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

(c): Downgraded by 2 increments if the confidence interval crosses 2 MIDs.

Table 13Clinical evidence summary: Stimulants + CBT versus CBT

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with CBT

Risk difference with Stimulants + CBT (95% CI)

ADHD symptoms (total, observer, ADHD-RS, 0-68, high is poor, FV, PT, >3 months)

303

(1 study)

16 weeks

HIGH

The mean ADHD symptoms (total, observer, ADHD-rs, 0-68, high is poor, fv, pt, >3 months) in the control groups was

16.4

The mean ADHD symptoms (total, observer, ADHD-rs, 0-68, high is poor, fv, pt, >3 months) in the intervention groups was

0.60 higher

(1.04 lower to 2.24 higher)

Table 14Clinical evidence summary: Mixed medication + PT/FT versus PT/FT

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with PF/FT

Risk difference with Mixed medication + PT/FT (95% CI)

ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

254

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean ADHD symptoms (total, teacher and parent, snap, high is poor, fv, fu >3 months) in the control groups was

1.27

The mean ADHD symptoms (total, teacher and parent, snap, high is poor, fv, fu >3 months) in the intervention groups was

0.07 lower

(0.21 lower to 0.07 higher)

ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

253

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, snap, high is poor, fv, pt, >3 months) in the control groups was

1.1

The mean ADHD symptoms (hyperactivity, teacher, snap, high is poor, fv, pt, >3 months) in the intervention groups was

0.35 lower

(0.53 to 0.17 lower)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

262

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean ADHD symptoms (hyperactivity, parent, snap, high is poor, fv, pt >3 months) in the control groups was

1.24

The mean ADHD symptoms (hyperactivity, parent, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.61 higher

(0.45 to 0.77 higher)

ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

221

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, snap, high is poor, fv, pt >3 months) in the control groups was

0.29

The mean ADHD symptoms (hyperactivity, observer, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.08 lower

(0.14 to 0.02 lower)

ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

262

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, snap, high is poor, fv, pt >3 months) in the control groups was

1.4

The mean ADHD symptoms (inattention, parent, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.38 lower

(0.54 to 0.22 lower)

ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

254

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, snap, high is poor, fv, pt >3 months) in the control groups was

1.47

The mean ADHD symptoms (inattention, teacher, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.35 lower

(0.54 to 0.16 lower)

Academic outcomes (maths accuracy %, high is better, observer, PT <3 months)

(1 study)

8 days

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean academic outcomes (maths accuracy %, observer, high is better, pt <3 months) in the control groups was

91.89

The mean academic outcomes (maths accuracy %, observer, high is better, pt <3 months) in the intervention groups was

0.99 lower

(3.42 lower to 1.44 higher)

Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

270

(1 study)

8 weeks

LOW^c

due to risk of bias

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132,high is better, pt >3 months) in the control groups was

100.3

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132,high is better, pt >3 months) in the intervention groups was

0.20 higher

(3.4 lower to 3.8 higher)

Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean academic outcomes (reading accuracy %, observer, high is better, pt <3 months) in the control groups was

91.59

The mean academic outcomes (reading accuracy %, observer, high is better, pt <3 months) in the intervention groups was

1.17 lower

(4.34 lower to 2 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

270

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

96.2

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132,high is better, pt >3 months) in the intervention groups was

3.20 higher

(0.39 lower to 6.79 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

254

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132,high is better, fu >3 months) in the control groups was

98.3

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132,high is better, fu >3 months) in the intervention groups was

0.60 lower

(4.02 lower to 2.82 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

(c): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 15Clinical evidence summary: Atomoxetine + PT/FT versus atomoxetine

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Atomoxetine

Risk difference with Atomoxetine + PT/FT (95% CI)

ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.24

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.01 lower

(0.32 lower to 0.3 higher)

ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.49

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.35 lower

(0.73 lower to 0.03 higher)

ADHD symptoms (hyperactivity, parent, multiple scales, higher is worse, FV, PT <3 months)

120

(2 studies)

8-10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, multiple scales, higher is worse, fv, pt <3 months) in the control groups was

1.19

The mean ADHD symptoms (hyperactivity, parent, multiple scales, higher is worse, fv, pt <3 months) in the intervention groups was

0.21 standard deviations lower

(0.57 lower to 0.15 higher)

ADHD symptoms (hyperactivity, teacher, multiple scales, higher is worse, FV, PT <3 months)

120

(2 studies)

8-10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, multiple scales, higher is worse, fv, pt <3 months) in the control groups was

1.13

The mean ADHD symptoms (hyperactivity, teacher, multiple scales, higher is worse, fv, pt <3 months) in the intervention groups was

0.16 standard deviations lower

(0.52 lower to 0.2 higher)

ADHD symptoms (inattention, parent, multiple scales, higher is worse, FV, PT <3 months)

120

(2 studies)

8-10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, multiple scales, higher is worse, fv, pt <3 months) in the control groups was

1.50

The mean ADHD symptoms (inattention, parent, multiple scales, higher is worse, fv, pt <3 months) in the intervention groups was

0.37 standard deviations lower

(0.73 to 0.01 lower)

ADHD symptoms (inattention, teacher, multiple scales, higher is worse, FV, PT <3 months)

120

(2 studies)

8-10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, multiple scales, higher is worse, fv, pt <3 months) in the control groups was

1.52

The mean ADHD symptoms (inattention, teacher, multiple scales, higher is worse, fv, pt <3 months) in the intervention groups was

0.38 standard deviations lower

(0.74 to 0.02 lower)

Responders by CGI-I (PT, <3 months)

119

(2 studies)

8-10 weeks

VERY LOW^a^,^c

due to risk of bias, imprecision

RR 1.05

(0.73 to 1.5)

Moderate

494 per 1000

25 more per 1000

(from 133 fewer to 247 more)

Behaviour/function (behaviour, 0-100, high is good, teacher, PT, <3 months)

(1 study)

8 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (behaviour, 0-100, high is good, teacher, pt, <3 months) in the control groups was

77.84

The mean behaviour/function (behaviour, 0-100, high is good, teacher, pt, <3 months) in the intervention groups was

5.06 higher

(4.59 lower to 14.71 higher)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

(c): Downgraded by 2 increments if the confidence interval crossed both MIDs.

Table 16Clinical evidence summary: Stimulants + PT/FT versus stimulants

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Stimulants

Risk difference with Stimulants + PT/FT (95% CI)

ADHD symptoms (total, parent, multiple scales, high is poor, FV, PT, >3 months)

224

(3 studies)

2-12 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, multiple scales, high is poor, fv, pt, >3 months) in the control groups was

4.44

The mean ADHD symptoms (total, parent, multiple scales, high is poor, fv, pt, >3 months) in the intervention groups was

0.42 standard deviations lower

(0.69 to 0.15 lower)

ADHD symptoms (total, parent, SWAN, 0-3, high is poor, FV, FU, >3 months)

(1 study)

12 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, swan, 0-3, high is poor, fv, fu, >3 months) in the control groups was

0.71

The mean ADHD symptoms (total, parent, swan, 0-3, high is poor, fv, fu, >3 months) in the intervention groups was

0.13 lower

(0.39 lower to 0.13 higher)

ADHD symptoms (total, teacher, DBDRS, 0-54, high is poor, FV, PT, <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, dbdrs, 0-54, high is poor, fv, pt, <3 months) in the control groups was

13.75

The mean ADHD symptoms (total, teacher, dbdrs, 0-54, high is poor, fv, pt, <3 months) in the intervention groups was

2.15 higher

(3.48 lower to 7.78 higher)

ADHD symptoms (hyperactivity, parent, FBB-ADHS, 0-3, high is poor, FV, PT, >3 months)

137

(2 studies)

12 months

MODERATE^a

due to risk of bias

The mean ADHD symptoms (hyperactivity, parent, fbbadhs, 0-3, high is poor, fv, pt, >3 months) in the control groups was

1.26

The mean ADHD symptoms (hyperactivity, parent, fbbadhs, 0-3, high is poor, fv, pt, >3 months) in the intervention groups was

0.05 standard deviations lower

(0.35 lower to 0.25 higher)

ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

(1 study)

12 months

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, fu >3 months) in the control groups was

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, fu >3 months) in the intervention groups was

0.10 lower

(0.36 lower to 0.16 higher)

ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

(1 study)

12 months

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, pt >3 months) in the control groups was

1.2

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, pt >3 months) in the intervention groups was

0.30 lower

(0.7 lower to 0.1 higher)

ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

(1 study)

12 months

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, fu >3 months) in the control groups was

1.1

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, fu >3 months) in the intervention groups was

0.10 lower

(0.46 lower to 0.26 higher)

ADHD symptoms (inattention, parent, FBB-ADHS, 0-3, high is poor, FV, PT, >3 months)

103

(1 study)

12 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, fbb-adhs, 0-3, high is poor, fv, pt, >3 months) in the control groups was

1.67

The mean ADHD symptoms (inattention, parent, fbb-adhs, 0-3, high is poor, fv, pt, >3 months) in the intervention groups was

0.29 lower

(0.53 to 0.05 lower)

Behaviour/function (function, parent, WFIRS-P, 0-3, high is poor, FV, PT, >3 months)

103

(1 study)

12 months

LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (function, parent, wfirs-p, 0-3, high is poor, fv, pt, >3 months) in the control groups was

0.96

The mean behaviour/function (function, parent, wfirs-p, 0-3, high is poor, fv, pt, >3 months) in the intervention groups was

0.10 lower

(0.3 lower to 0.1 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

(c): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 17Clinical evidence summary: Stimulants + PT/FT versus stimulants + NSST

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with stimulants + NSST

Risk difference with Stimulants + PT/FT versus stimulants + NSST (95% CI)

ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, pt >3 months) in the control groups was

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, pt >3 months) in the intervention groups was

0.20 higher

(0.08 lower to 0.48 higher)

ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, fu >3 months) in the control groups was

0.8

The mean ADHD symptoms (hyperactivity, parent, ctrs, 0-3, higher is worse, fv, fu >3 months) in the intervention groups was

0.10 higher

(0.11 lower to 0.31 higher)

ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

(1 study)

12 months

LOW^a

due to risk of bias

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, pt >3 months) in the control groups was

0.9

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, pt >3 months) in the intervention groups was

0 higher

(0.36 lower to 0.36 higher)

ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

(1 study)

12 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, fu >3 months) in the control groups was

0.7

The mean ADHD symptoms (hyperactivity, teacher, ctrs, 0-3, higher is worse, fv, fu >3 months) in the intervention groups was

0.30 higher

(0.03 to 0.57 higher)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

Table 18Clinical evidence summary: Stimulants + attention/memory/cognitive training compared to stimulants

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Stimulants

Risk difference with Stimulants + attention/memory/cognitive training (95% CI)

ADHD symptoms (total, parent, Conners 48, 0-70, high is poor, FV, <3 months PT)

(1 study)

<3 months

LOW^a

due to risk of bias

The mean ADHD symptoms (total, parent, conners 48, high is poor, fv, <3 months pt) in the control groups was

58.4

The mean ADHD symptoms (total, parent, conners 48, high is poor, fv, <3 months pt) in the intervention groups was

8.67 lower

(11.5 to 5.84 lower)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 19Clinical evidence summary: Stimulants + NF versus stimulants

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Stimulants

Risk difference with Stimulants + NF (95% CI)

ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

28.1

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

3.50 lower

(7.57 lower to 0.57 higher)

ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

23.5

The mean ADHD symptoms (total, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.80 lower

(5.67 lower to 4.07 higher)

ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

23.7

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.60 lower

(8.51 lower to 3.31 higher)

ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

26.1

The mean ADHD symptoms (total, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

4.00 lower

(9.55 lower to 1.55 higher)

ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

12.2

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.70 lower

(5.14 to 0.26 lower)

ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

11.4

The mean ADHD symptoms (hyperactivity, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.50 lower

(3.27 lower to 2.27 higher)

ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

11.2

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

2.50 lower

(6.37 lower to 1.37 higher)

ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

13.1

The mean ADHD symptoms (hyperactivity, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

1.50 lower

(5.64 lower to 2.64 higher)

ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, <3 months) in the control groups was

6.4

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, <3 months) in the intervention groups was

0.60 higher

(0.83 lower to 2.03 higher)

ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, >3 months) in the control groups was

5.9

The mean ADHD symptoms (hyperactivity, self-rated, srq, 1-10, high is poor, pt, >3 months) in the intervention groups was

0.00 higher

(1.22 lower to 1.22 higher)

ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self, srq, 1-10, high is good, cs, pt <3 months) in the control groups was

1.3

The mean ADHD symptoms (hyperactivity, self, srq, 1-10, high is good, cs, pt <3 months) in the intervention groups was

0.30 lower

(1.87 lower to 1.27 higher)

ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, <3 months) in the control groups was

15.9

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, <3 months) in the intervention groups was

0.80 lower

(3.05 lower to 1.45 higher)

ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, >3 months) in the control groups was

12.1

The mean ADHD symptoms (inattention, parent, barkley’s, high is poor, pt, >3 months) in the intervention groups was

0.30 lower

(2.94 lower to 0 higher)

ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, <3 months) in the control groups was

12.5

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, <3 months) in the intervention groups was

0.10 lower

(3.16 lower to 2.96 higher)

ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, >3 months) in the control groups was

13.1

The mean ADHD symptoms (inattention, teacher, barkley’s, high is poor, pt, >3 months) in the intervention groups was

1.50 lower

(4.48 lower to 1.48 higher)

ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, <3 months) in the control groups was

6.7

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, <3 months) in the intervention groups was

0.40 lower

(1.62 lower to 0.82 higher)

ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, FU, >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, >3 months) in the control groups was

The mean ADHD symptoms (inattention, self-rated, srq, 1-10, high is poor, pt, >3 months) in the intervention groups was

0.90 higher

(0.18 lower to 1.98 higher)

ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self, srq, 1-10, high is good, cs, pt <3 months) in the control groups was

1.4

The mean ADHD symptoms (inattention, self, srq, 1-10, high is good, cs, pt <3 months) in the intervention groups was

0.20 lower

(1.58 lower to 1.18 higher)

Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

(1 study)

<3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, cs, pt <3 months) in the control groups was

0.1

The mean academic (general, self, 1-10, high is good, cs, pt <3 months) in the intervention groups was

1.10 lower

(2.84 lower to 0.64 higher)

Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

(1 study)

3 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, pt <3 months) in the control groups was

6.4

The mean academic (general, self, 1-10, high is good, pt <3 months) in the intervention groups was

0.60 higher

(0.83 lower to 2.03 higher)

Academic (general, self, SRQ, 1-10, high is good, FU >3 months)

(1 study)

6 months

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean academic (general, self, 1-10, high is good, pt >3 months) in the control groups was

5.9

The mean academic (general, self, 1-10, high is good, pt >3 months) in the intervention groups was

0.00 higher

(1.22 lower to 1.22 higher)

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

(c): Downgraded by 2 increments if the confidence interval crossed both MIDs.

Table 20Clinical evidence summary: Mixed medication + PT/FT versus mixed medication

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Mixed medication

Risk difference with Mixed medication + PT/FT (95% CI)

ADHD symptoms (total, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

270

(1 study)

12 months

VERY LOW^b^,^c

due to risk of bias, imprecision

1 Control group results unavailable

The mean ADHD symptoms (total, parent, 0-54, high is poor, cs, fu, >3 months) in the intervention groups was

0.27 standard deviations lower

(0.51 to 0.03 lower)

ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

242

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean ADHD symptoms (total, teacher and parent, snap, high is poor, fv, fu >3 months) in the control groups was

1.21

The mean ADHD symptoms (total, teacher and parent, snap, high is poor, fv, fu >3 months) in the intervention groups was

0.01 lower

(0.15 lower to 0.13 higher)

ADHD symptoms (hyperactivity, teacher, Conner’s, 0-20, high is poor, FV, PT, <3 months)

(1 study)

3 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, conner’s, high is poor, fv, pt, <3 months) in the control groups was

13.93

The mean ADHD symptoms (hyperactivity, teacher, conner’s, high is poor, fv, pt, <3 months) in the intervention groups was

2.22 higher

(4.38 lower to 8.82 higher)

ADHD symptoms (hyperactivity, teacher, multiple scales, high is poor, FV, PT, >3 months)

309

(2 studies)

3-14 months

MODERATE^b

due to risk of bias

The mean ADHD symptoms (hyperactivity, teacher, multiple scales, high is poor, fv, pt, >3 months) in the control groups was

3.13

The mean ADHD symptoms (hyperactivity, teacher, multiple scales, high is poor, fv, pt, >3 months) in the intervention groups was

0.05 standard deviations lower

(0.28 lower to 0.17 higher)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

254

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean ADHD symptoms (hyperactivity, parent, snap, high is poor, fv, pt >3 months) in the control groups was

0.91

The mean ADHD symptoms (hyperactivity, parent, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.94 higher

(0.78 to 1.1 higher)

ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

224

(1 study)

14 months

LOW^b^,^c

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, snap, high is poor, fv, pt >3 months) in the control groups was

0.16

The mean ADHD symptoms (hyperactivity, observer, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.05 higher

(0 to 0.1 higher)

ADHD symptoms (hyperactivity, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

270

(1 study)

12 months

LOW^d

due to risk of bias

1 Control group results unavailable

The mean ADHD symptoms (hyperactivity, parent, 0-54, high is poor, cs, fu, >3 months) in the intervention groups was

0.22 standard deviations lower

(0.46 lower to 0.02 higher)

ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

254

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean ADHD symptoms (inattention, parent, snap, high is poor, fv, pt >3 months) in the control groups was

1.12

The mean ADHD symptoms (inattention, parent, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.10 lower

(0.27 lower to 0.07 higher)

ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

254

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean ADHD symptoms (inattention, teacher, snap, high is poor, fv, pt >3 months) in the control groups was

1.11

The mean ADHD symptoms (inattention, teacher, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.01 higher

(0.18 lower to 0.2 higher)

ADHD symptoms (inattention, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

270

(1 study)

12 months

VERY LOW^c^,^d

due to risk of bias, imprecision

1 Control group results unavailable

The mean ADHD symptoms (inattention, parent, 0-54, high is poor, cs, fu, >3 months) in the intervention groups was

0.27 standard deviations lower

(0.51 to 0.03 lower)

Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT <3 months)

(1 study)

3 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean behaviour/function (cbrs aggressive behaviour subscale, high is poor, teacher, pt <3 months) in the control groups was

11.58

The mean behaviour/function (cbrs aggressive behaviour subscale, high is poor, teacher, pt <3 months) in the intervention groups was

1.58 lower

(8.11 lower to 4.95 higher)

Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT >3 months)

(1 study)

6 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean behaviour/function (cbrs aggressive behaviour subscale, high is poor, teacher, pt >3 months) in the control groups was

12.78

The mean behaviour/function (cbrs aggressive behaviour subscale, high is poor, teacher, pt >3 months) in the intervention groups was

2.28 lower

(8.8 lower to 4.24 higher)

Emotional dysregulation (CBRS emotional distress subscale, 0-20, high is poor, teacher, PT <3 months)

(1 study)

3 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean emotional dysregulation (cbrs emotional distress subscale, high is poor, teacher, pt <3 months) in the control groups was

13.04

The mean emotional dysregulation (cbrs emotional distress subscale, high is poor, teacher, pt <3 months) in the intervention groups was

4.22 higher

(2.14 lower to 10.58 higher)

Emotional dysregulation (CBRS emotional distress subscale, 0-20, high is poor, teacher, PT >3 months)

(1 study)

6 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean emotional dysregulation (cbrs emotional distress subscale, high is poor, teacher, pt >3 months) in the control groups was

14.44

The mean emotional dysregulation (cbrs emotional distress subscale, high is poor, teacher, pt >3 months) in the intervention groups was

2.35 higher

(4.16 lower to 8.86 higher)

Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean academic outcomes (maths accuracy %, observer, high is better, pt <3 months) in the control groups was

87.75

The mean academic outcomes (maths accuracy %, observer, high is better, pt <3 months) in the intervention groups was

3.15 higher

(0.15 to 6.15 higher)

Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

260

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

99.7

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the intervention groups was

0.80 higher

(2.78 lower to 4.38 higher)

Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean academic outcomes (reading accuracy %, observer, high is better, pt <3 months) in the control groups was

86.14

The mean academic outcomes (reading accuracy %, observer, high is better, pt <3 months) in the intervention groups was

4.28 higher

(0.3 to 8.26 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

260

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

97.9

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the intervention groups was

1.50 higher

(2.06 lower to 5.06 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

242

(1 study)

14 months

MODERATE^b

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, fu >3 months) in the control groups was

97.8

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, fu >3 months) in the intervention groups was

0.10 lower

(3.53 lower to 3.33 higher)

Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT <3 months)

(1 study)

3 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean academic outcomes (general, cbrs academic subscale, high is poor, teacher, pt <3 months) in the control groups was

17.88

The mean academic outcomes (general, cbrs academic subscale, high is poor, teacher, pt <3 months) in the intervention groups was

2.25 higher

(4.95 lower to 9.45 higher)

Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT >3 months)

(1 study)

6 months

VERY LOW^c^,^d

due to risk of bias, imprecision

The mean academic outcomes (general, cbrs academic subscale, high is poor, teacher, pt >3 months) in the control groups was

21.52

The mean academic outcomes (general, cbrs academic subscale, high is poor, teacher, pt >3 months) in the intervention groups was

0.48 lower

(7.09 lower to 6.13 higher)

(a): Control group not available.

(b): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(c): Downgraded by 1 increment if the confidence interval crossed 1MID.

(d): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 21Clinical evidence summary: Mixed medication + CBT versus mixed medication

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Mixed medication

Risk difference with Mixed medication + CBT (95% CI)

ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

(1 study)

4 months

MODERATE^b

due to risk of bias

1 Control group results unavailable

The mean ADHD symptoms (total, self, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was

1.08 standard deviations lower

(1.52 to 0.64 lower)

ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

119

(1 study)

12 sessions

LOW^c

due to risk of bias

The mean ADHD symptoms (total, self, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the control groups was

26.09

The mean ADHD symptoms (total, self, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the intervention groups was

7.62 lower

(7.98 to 7.26 lower)

ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

119

(1 study)

12 sessions

LOW^c

due to risk of bias

The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the control groups was

28.44

The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the intervention groups was

9.39 lower

(9.79 to 8.99 lower)

ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

(1 study)

4 months

MODERATE^b

due to risk of bias

1 Control group results unavailable

The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was

2.21 standard deviations lower

(2.74 to 1.69 lower)

ADHD symptoms (hyperactivity, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

119

(1 study)

12 sessions

LOW^c

due to risk of bias

The mean ADHD symptoms (hyperactivity, self, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the control groups was

11.72

The mean ADHD symptoms (hyperactivity, self, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the intervention groups was

3.43 lower

(3.74 to 3.12 lower)

ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

119

(1 study)

12 sessions

LOW^c

due to risk of bias

The mean ADHD symptoms (hyperactivity, parent, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the control groups was

11.56

The mean ADHD symptoms (hyperactivity, parent, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the intervention groups was

3.84 lower

(4.12 to 3.56 lower)

ADHD symptoms (inattention, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

119

(1 study)

12 sessions

LOW^c

due to risk of bias

The mean ADHD symptoms (inattention, self, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the control groups was

14.47

The mean ADHD symptoms (inattention, self, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the intervention groups was

4.33 lower

(4.51 to 4.15 lower)

ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

119

(1 study)

12 sessions

LOW^c

due to risk of bias

The mean ADHD symptoms (inattention, parent, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the control groups was

16.99

The mean ADHD symptoms (inattention, parent, ADHD-rs, 0-54, high is poor, fv, pt >3 months) in the intervention groups was

5.68 lower

(5.89 to 5.47 lower)

1: Control group not available.

2: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(a): Control group not available.

(b): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(c): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 22Clinical evidence summary: Mixed medication + PE versus mixed medication + NSST

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Mixed medication + NSST

Risk difference with Mixed medication + PE (95% CI)

ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

(1 study)

12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, cprs, 0-27, high is poor, fv, pt <3 months) in the control groups was

8.45

The mean ADHD symptoms (hyperactivity, parent, cprs, 0-27, high is poor, fv, pt <3 months) in the intervention groups was

1.71 lower

(3.67 lower to 0.25 higher)

ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

(1 study)

64 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, cprs, 0-27, high is poor, fv, fu >3 months) in the control groups was

8.47

The mean ADHD symptoms (hyperactivity, parent, cprs, 0-27, high is poor, fv, fu >3 months) in the intervention groups was

1.07 lower

(3.02 lower to 0.88 higher)

ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

(1 study)

12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, cprs, 0-27, high is poor, fv, pt <3 months) in the control groups was

The mean ADHD symptoms (inattention, parent, cprs, 0-27, high is poor, fv, pt <3 months) in the intervention groups was

3.05 lower

(4.63 to 1.47 lower)

ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

(1 study)

64 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, cprs, 0-27, high is poor, fv, fu >3 months) in the control groups was

10.41

The mean ADHD symptoms (inattention, parent, cprs, 0-27, high is poor, fv, fu >3 months) in the intervention groups was

2.15 lower

(3.93 to 0.37 lower)

Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

(1 study)

12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (opposition, parent, cprs, 0-27, high is poor, fv, pt <3 months) in the control groups was

6.18

The mean behaviour/function (opposition, parent, cprs, 0-27, high is poor, fv, pt <3 months) in the intervention groups was

1.23 lower

(2.94 lower to 0.48 higher)

Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

(1 study)

64 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (opposition, parent, cprs, 0-27, high is poor, fv, fu >3 months) in the control groups was

5.63

The mean behaviour/function (opposition, parent, cprs, 0-27, high is poor, fv, fu >3 months) in the intervention groups was

0.43 lower

(2.21 lower to 1.35 higher)

Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, PT <3 months)

(1 study)

12 weeks

MODERATE^a

due to risk of bias

The mean emotional dysregulation (sdq, parent, 0-25, high is poor, fv, pt <3 months) in the control groups was

3.5

The mean emotional dysregulation (sdq, parent, 0-25, high is poor, fv, pt <3 months) in the intervention groups was

0.11 lower

(1.21 lower to 0.99 higher)

Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, FU >3 months)

(1 study)

64 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean emotional dysregulation (sdq, parent, 0-25, high is poor, fv, fu >3 months) in the control groups was

3.75

The mean emotional dysregulation (sdq, parent, 0-25, high is poor, fv, fu >3 months) in the intervention groups was

0.29 lower

(1.32 lower to 0.74 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

Table 23Clinical evidence summary: Mixed medication + sleep intervention versus mixed medication

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Mixed medication	Risk difference with Mixed medication + sleep intervention (95% CI)
ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)	244 (1 study) 3 months	LOW^b due to risk of bias		1 Control group results unavailable	The mean ADHD symptoms (total, teacher, ADHD-rs, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.21 standard deviations lower (0.46 lower to 0.04 higher)
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)	244 (1 study) 3 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.39 standard deviations lower (0.64 to 0.13 lower)
ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)	244 (1 study) 6 months	LOW^b due to risk of bias		1 Control group results unavailable	The mean ADHD symptoms (total, teacher, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was 0.18 standard deviations lower (0.43 lower to 0.07 higher)
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)	244 (1 study) 6 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was 0.41 standard deviations lower (0.66 to 0.15 lower)
ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)	244 (1 study) 3 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (hyperactivity, teacher, ADHD-rs, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.28 standard deviations lower (0.53 to 0.03 lower)
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)	244 (1 study) 3 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (hyperactivity, parent, ADHD-rs, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.27 standard deviations lower (0.52 to 0.02 lower)
ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)	244 (1 study) 6 weeks	LOW^b due to risk of bias		1 Control group results unavailable	The mean ADHD symptoms (hyperactivity, teacher, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was 0.18 standard deviations lower (0.44 lower to 0.07 higher)
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)	244 (1 study) 6 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (hyperactivity, parent, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was 0.29 standard deviations lower (0.54 to 0.04 lower)
ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)	244 (1 study) 3 months	LOW^b due to risk of bias		1 Control group results unavailable	The mean ADHD symptoms (inattention, teacher, ADHD-rs, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.11 standard deviations lower (0.36 lower to 0.14 higher)
ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)	244 (1 study) 3 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (inattention, parent, ADHD-rs, 0-54, high is poor, cs, pt <3 months) in the intervention groups was 0.43 standard deviations lower (0.68 to 0.18 lower)
ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)	244 (1 study) 6 months	LOW^b due to risk of bias		1 Control group results unavailable	The mean ADHD symptoms (inattention, teacher, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was 0.11 standard deviations lower (0.36 lower to 0.14 higher)
ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)	244 (1 study) 6 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean ADHD symptoms (inattention, parent, ADHD-rs, 0-54, high is poor, cs, pt >3 months) in the intervention groups was 0.46 standard deviations lower (0.72 to 0.21 lower)
Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, <3 months PT	244 (1 study) 3 months	LOW^b due to risk of bias		1 Control group results unavailable	The mean behaviour/function (teacher, sdq, 0-54, high is poor, cs, <3 months pt in the intervention groups was 0.25 standard deviations lower (0.5 lower to 0 higher)
Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, >3 months PT	244 (1 study) 6 months	VERY LOW^b^,^c due to risk of bias, imprecision		1 Control group results unavailable	The mean behaviour/function (teacher, sdq, 0-54, high is poor, cs, >3 months pt in the intervention groups was 0.32 standard deviations lower (0.57 to 0.06 lower)

(a): No control group data available.

(b): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(c): Downgraded by 1 increment if the confidence interval crossed 1MID.

Table 24Clinical evidence summary: Mixed medication + NF compared to mixed medication

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Mixed medication

Risk difference with Mixed medication + NF (95% CI)

ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, fv, pt <3 months) in the control groups was

15.22

The mean ADHD symptoms (total, parent, ADHD-rs, 0-54, high is poor, fv, pt <3 months) in the intervention groups was

4.44 lower

(7.07 to 1.81 lower)

Behaviour/function (CBRS, parent, unclear scale, high is poor, FV, PT <3 months)

(1 study)

10 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (cbrs, parent, unclear scale, high is poor, fv, pt <3 months) in the control groups was

11.33

The mean behaviour/function (cbrs, parent, unclear scale, high is poor, fv, pt <3 months) in the intervention groups was

3.72 lower

(6.96 to 0.48 lower)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID.

Table 25Clinical evidence summary: Atomoxetine + PT/FT versus placebo/usual care

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Placebo/usual care

Risk difference with Atomoxetine + PT/FT (95% CI)

ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.74

The mean ADHD symptoms (total, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.51 lower

(0.89 to 0.13 lower)

ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.44

The mean ADHD symptoms (total, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.30 lower

(0.71 lower to 0.11 higher)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.69

The mean ADHD symptoms (hyperactivity, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.54 lower

(0.96 to 0.12 lower)

ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.25

The mean ADHD symptoms (hyperactivity, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.27 lower

(0.72 lower to 0.18 higher)

ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.79

The mean ADHD symptoms (inattention, parent, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.49 lower

(0.87 to 0.11 lower)

ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the control groups was

1.63

The mean ADHD symptoms (inattention, teacher, snap, 0-3, higher is worse, fv, pt <3 months) in the intervention groups was

0.33 lower

(0.78 lower to 0.12 higher)

Responders by CGI-I (PT, <3 months)

(1 study)

10 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

RR 2.5

(1.12 to 5.59)

Moderate

194 per 1000

291 more per 1000

(from 23 more to 890 more)

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

(a): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

Table 26Clinical evidence summary: Mixed medication + PT/FT versus placebo/usual care

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Placebo/usual care

Risk difference with Mixed medication + PT/FT (95% CI)

ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

243

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean ADHD symptoms (total, teacher and parent, snap, high is poor, fv, fu >3 months) in the control groups was

1.26

The mean ADHD symptoms (total, teacher and parent, snap, high is poor, fv, fu >3 months) in the intervention groups was

0.06 lower

(0.2 lower to 0.08 higher)

ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

262

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, teacher, snap, high is poor, fv, pt, >3 months) in the control groups was

1.25

The mean ADHD symptoms (hyperactivity, teacher, snap, high is poor, fv, pt, >3 months) in the intervention groups was

0.50 lower

(0.69 to 0.31 lower)

ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

263

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, parent, snap, high is poor, fv, pt >3 months) in the control groups was

1.35

The mean ADHD symptoms (hyperactivity, parent, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.50 higher

(0.34 to 0.66 higher)

ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

223

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean ADHD symptoms (hyperactivity, observer, snap, high is poor, fv, pt >3 months) in the control groups was

0.18

The mean ADHD symptoms (hyperactivity, observer, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.03 higher

(0.02 lower to 0.08 higher)

ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

263

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, parent, snap, high is poor, fv, pt >3 months) in the control groups was

1.49

The mean ADHD symptoms (inattention, parent, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.47 lower

(0.63 to 0.31 lower)

ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

262

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, teacher, snap, high is poor, fv, pt >3 months) in the control groups was

1.48

The mean ADHD symptoms (inattention, teacher, snap, high is poor, fv, pt >3 months) in the intervention groups was

0.36 lower

(0.55 to 0.17 lower)

Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean academic outcomes (maths accuracy%, observer, high is better, pt <3 months) in the control groups was

83.85

The mean academic outcomes (maths accuracy%, observer, high is better, pt <3 months) in the intervention groups was

7.05 higher

(3.69 to 10.41 higher)

Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

267

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

100.4

The mean academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, pt >3 months) in the intervention groups was

0.10 higher

(3.69 lower to 3.89 higher)

Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

(1 study)

8 weeks

VERY LOW^b^,^c

due to risk of bias, imprecision

The mean academic outcomes (reading accuracy, %, observer, high is better, pt <3 months) in the control groups was

82.76

The mean academic outcomes (reading accuracy, %, observer, high is better, pt <3 months) in the intervention groups was

7.66 higher

(3.35 to 11.97 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

267

(1 study)

14 months

LOW^a^,^b

due to risk of bias, imprecision

The mean academic outcomes (reading accuracy,, observer, WIAT, 0-132, high is better, pt >3 months) in the control groups was

95.4

The mean academic outcomes (reading accuracy,, observer, WIAT, 0-132, high is better, pt >3 months) in the intervention groups was

4.00 higher

(0.47 to 7.53 higher)

Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

243

(1 study)

14 months

MODERATE^a

due to risk of bias

The mean academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, fu >3 months) in the control groups was

The mean academic outcomes (reading accuracy,, observer, WIAT, 0-132, high is better, fu >3 months) in the intervention groups was

1.70 higher

(1.87 lower to 5.27 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1MID.

(c): Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 27Clinical evidence summary: Stimulants + NF versus stimulants + attention/memory/cognitive training

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Stimulants + attention/memory/cognitive training

Risk difference with Stimulants + NF (95% CI)

ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

(1 study)

8-20 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (total, parent, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the control groups was

41.2

The mean ADHD symptoms (total, parent, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the intervention groups was

2.60 lower

(6.97 lower to 1.77 higher)

ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

(1 study)

8-20 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (total, teacher, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the control groups was

41.8

The mean ADHD symptoms (total, teacher, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the intervention groups was

3.90 lower

(8.79 lower to 0.99 higher)

ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

(1 study)

6 months

MODERATE^a

due to imprecision

The mean ADHD symptoms (total, parent, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the control groups was

44.9

The mean ADHD symptoms (total, parent, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the intervention groups was

7.00 lower

(10.85 to 3.15 lower)

ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

(1 study)

6 months

MODERATE^a

due to imprecision

The mean ADHD symptoms (total, teacher, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the control groups was

43.7

The mean ADHD symptoms (total, teacher, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the intervention groups was

8.70 lower

(13.12 to 4.28 lower)

ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

(1 study)

8-20 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (hyperactivity, parent, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the control groups was

17.3

The mean ADHD symptoms (hyperactivity, parent, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the intervention groups was

0.70 lower

(3.42 lower to 2.02 higher)

ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

(1 study)

8-20 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (hyperactivity, teacher, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the control groups was

18.4

The mean ADHD symptoms (hyperactivity, teacher, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the intervention groups was

1.60 lower

(4.57 lower to 1.37 higher)

ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

(1 study)

6 months

MODERATE^a

due to imprecision

The mean ADHD symptoms (hyperactivity, parent, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the control groups was

19.2

The mean ADHD symptoms (hyperactivity, parent, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the intervention groups was

3.20 lower

(5.83 to 0.57 lower)

ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

(1 study)

6 months

MODERATE^a

due to imprecision

The mean ADHD symptoms (hyperactivity, teacher, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the control groups was

19.8

The mean ADHD symptoms (hyperactivity, teacher, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the intervention groups was

3.70 lower

(6.89 to 0.51 lower)

ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

(1 study)

8-20 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (inattention, parent, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the control groups was

23.9

The mean ADHD symptoms (inattention, parent, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the intervention groups was

1.30 lower

(3.83 lower to 1.23 higher)

ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

(1 study)

8-20 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (inattention, teacher, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the control groups was

23.6

The mean ADHD symptoms (inattention, teacher, dsm-iv, high is poor, unclear scale, fv, pt <3 months) in the intervention groups was

2.40 lower

(5.1 lower to 0.3 higher)

ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

(1 study)

6 weeks

MODERATE^a

due to imprecision

The mean ADHD symptoms (inattention, parent, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the control groups was

25.7

The mean ADHD symptoms (inattention, parent, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the intervention groups was

4.10 lower

(6.43 to 1.77 lower)

ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

(1 study)

6 months

HIGH

The mean ADHD symptoms (inattention, teacher, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the control groups was

25.4

The mean ADHD symptoms (inattention, teacher, dsm-iv, high is poor, unclear scale, fv, fu >3 months) in the intervention groups was

5.50 lower

(7.4 to 3.6 lower)

(a): Downgraded by 1 increment if the confidence interval crossed 1 MID.

Table 28Clinical evidence summary: stimulants + NSST versus CBT

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with CBT

Risk difference with Stimulants + NSST (95% CI)

ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

213

(1 study)

1 years

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the CBT groups was

16.9

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the intervention groups was

1.80 lower

(3.63 lower to 0.03 higher)

ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

210

(1 study)

1 years

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, observer, caars, high is worse, fv, >3 months pt) in the CBT groups was

16.4

The mean ADHD symptoms (total, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

1.80 lower

(3.49 to 0.11 lower)

ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

210

(1 study)

1 years

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the CBT groups was

14.9

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

1.60 lower

(3.41 lower to 0.21 higher)

ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

213

(1 study)

1 years

MODERATE^a

due to risk of bias

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the CBT groups was

15.2

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

0.80 higher

(0.95 lower to 2.55 higher)

Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

210

(1 study)

1 years

MODERATE^a

due to risk of bias

The mean emotional dysregulation (bdi, 0-63, high is poor, fv, >3 months pt) in the CBT groups was

9.4

The mean emotional dysregulation (bdi, 0-63, high is poor, fv, >3 months pt) in the intervention groups was

0.20 higher

(1.77 lower to 2.17 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs.

Table 29Clinical evidence summary: stimulants + CBT/DBT versus CBT/DBT alone

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with CBT/DBT alone

Risk difference with Stimulants + CBT/DBT (95% CI)

ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

209

(1 study)

1 years

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the control groups was

16.9

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the intervention groups was

1.60 lower

(2.50 to 0.70 lower)

ADHD symptoms (total, self, multiple tools, decreased by >30%, >3 months PT) - General population

106

(1 study)

14 weeks

LOW^b

due to imprecision

RR 0.86

(0.59 to 1.26)

Moderate

547 per 1000

77 fewer per 1000

(from 224 fewer to 142 more)

ADHD symptoms (total, self, multiple tools, decreased by >30%, >3 months PT) - Secure estate

(1 study)

24 weeks

LOW^a^,^b

due to risk of bias, imprecision

RR 2.34

(1.17 to 4.69)

Moderate

269 per 1000

360 more per 1000

(from 46 more to 993 more)

ADHD symptoms (total, observer, TAADDS, decreased by >30%, >3 months PT)

106

(1 study)

14 weeks

MODERATE^a

due to imprecision

RR 1.4

(0.81 to 2.41)

Moderate

283 per 1000

113 more per 1000

(from 54 fewer to 399 more)

ADHD symptoms (total, observer, multiple tools, high is worse, FV, >3 months PT)

257

(2 studies)

20-52 weeks

LOW^a^,^b

due to risk of bias, imprecision

Control group results unavailable

The mean ADHD symptoms (total, observer, multiple tools, high is worse, fv, >3 months pt) in the intervention groups was

0.43 standard deviations lower

(0.67 to 0.18 lower)

ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

209

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the control groups was

14.9

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

1.90 lower

(2.84 to 0.96 lower)

ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

209

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the control groups was

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

1.00 lower

(1.92 to 0.08 lower)

Emotional dysregulation (multiple tools, high is poor, FV, >3 months PT)

257

(2 studies)

20-52 weeks

MODERATE^a

due to risk of bias

Control group results unavailable

The mean emotional dysregulation (multiple tools, high is poor, fv, >3 months pt) in the intervention groups was

0.06 standard deviations lower

(0.3 lower to 0.19 higher)

Responders by CGI-I (>3 months PT)

106

(1 study)

14 weeks

LOW^b

due to imprecision

RR 1.12

(0.65 to 1.96)

Moderate

302 per 1000

36 more per 1000

(from 106 fewer to 290 more)

Responders by CGI-I (>3 months FU)

(1 study)

20 weeks

HIGH

RR 4.08

(1.58 to 10.5)

Moderate

160 per 1000

493 more per 1000

(from 93 more to 1000 more)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 30Clinical evidence summary: stimulants + CBT/DBT + PT/FT versus NSST + PT/FT alone

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with NSST + PT/FT

Risk difference with Stimulants + CBT/DBT + PT/FT (95% CI)

ADHD symptoms (total, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

143

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, observer, caars, 0-36, high is poor, fv, >3 months pt) in the control groups was

15.8

The mean ADHD symptoms (total, observer, caars, 0-36, high is poor, fv, >3 months pt) in the intervention groups was

2.70 lower

(4.58 to 0.82 lower)

ADHD symptoms (hyperactivity, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

143

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, caars, 0-36, high is poor, fv, >3 months pt) in the control groups was

13.7

The mean ADHD symptoms (hyperactivity, observer, caars, 0-36, high is poor, fv, >3 months pt) in the intervention groups was

3.00 lower

(4.88 to 1.12 lower)

ADHD symptoms (inattention, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

143

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, observer, caars, 0-36, high is poor, fv, >3 months pt) in the control groups was

15.1

The mean ADHD symptoms (inattention, observer, caars, 0-36, high is poor, fv, >3 months pt) in the intervention groups was

2.70 lower

(4.79 to 0.61 lower)

Child’s ADHD symptoms (total, parent, SDQ, 0-10, high is poor, FV, >3 months PT)

144

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean child’s ADHD symptoms (total, parent, sdq, 0-10, high is poor, fv, >3 months pt) in the control groups was

6.2

The mean child’s ADHD symptoms (total, parent, sdq, 010, high is poor, fv, >3 months pt) in the intervention groups was

0.50 lower

(1.13 lower to 0.13 higher)

Emotional dysregulation (parent, SDQ, 0-10, high is poor, FV, >3 months PT)

144

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean emotional dysregulation (parent, sdq, 0-10, high is poor, fv, >3 months pt) in the control groups was

3.1

The mean emotional dysregulation (parent, sdq, 0-10, high is poor, fv, >3 months pt) in the intervention groups was

0.20 higher

(0.43 lower to 0.83 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 31Clinical evidence summary: stimulants + CBT/DBT versus stimulants + NSST alone

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Stimulants + NSST

Risk difference with Stimulants + CBT/DBT (95% CI)

ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

213

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the control groups was

15.1

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the intervention groups was

0.20 higher

(1.55 lower to 1.95 higher)

ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

213

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean ADHD symptoms (total, observer, caars, high is worse, fv, >3 months pt) in the control groups was

14.6

The mean ADHD symptoms (total, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

0.30 higher

(1.45 lower to 2.05 higher)

ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

209

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the control groups was

13.3

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

0.30 lower

(1.98 lower to 1.38 higher)

ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

209

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the control groups was

15.2

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

0.20 lower

(1.88 lower to 1.48 higher)

Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

213

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean emotional dysregulation (bdi, 0-63, high is poor, fv, >3 months pt) in the control groups was

9.6

The mean emotional dysregulation (bdi, 0-63, high is poor, fv, >3 months pt) in the intervention groups was

0.70 lower

(2.66 lower to 1.26 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 32Clinical evidence summary: mixed medication + CBT/DBT versus mixed medication alone

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with mixed medication alone

Risk difference with mixed medication + CBT/DBT (95% CI)

QoL (Flanagan, 16-112, high is good, FV, <3 months PT)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean qol (flanagan, 16-112, high is good, fv, <3 months pt) in the control groups was

70.9

The mean qol (flanagan, 16-112, high is good, fv, <3 months pt) in the intervention groups was

3.60 higher

(3.68 lower to 10.88 higher)

QoL (Flanagan, 16-112, high is good, FV, <3 months FU)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean qol (flanagan, 16-112, high is good, fv, <3 months fu) in the control groups was

72.22

The mean qol (flanagan, 16-112, high is good, fv, <3 months fu) in the intervention groups was

7.62 higher

(1.03 to 14.21 higher)

ADHD symptoms (total, observer, ADHD-RS, 0-54, higher is worse, FV, PT >3 months)

(1 study)

15 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, observer, ADHD-rs, 0-54, higher is worse, fv, pt >3 months) in the control groups was

20.8

The mean ADHD symptoms (total, observer, ADHD-rs, 0-54, higher is worse, fv, pt >3 months) in the intervention groups was

5.61 lower

(12.11 lower to 0.89 higher)

ADHD symptoms (total, self, ADHD-RS, 0-54, higher is worse, FV, PT >3 months)

(1 study)

15 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, self, ADHD-rs, 0-54, higher is worse, fv, pt >3 months) in the control groups was

23.87

The mean ADHD symptoms (total, self, ADHD-rs, 0-54, higher is worse, fv, pt >3 months) in the intervention groups was

9.12 lower

(15.69 to 2.55 lower)

ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months PT)

104

(2 studies)

8-12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, self, barkley, 0-54, high is poor, fv, <3 months pt) in the control groups was 21.57

The mean ADHD symptoms (total, self, barkley, 0-54, high is poor, fv, <3 months pt) in the intervention groups was

5.01 lower (8.30 to 1.72 lower)

ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months FU)

(2 studies)

12 weeks

VERY LOW^a^,^b

due to risk of bias,

The mean ADHD symptoms (total, self, barkley, 0-54, high is poor, fv, <3 months fu) in the control groups was 22.34

The mean ADHD symptoms (total, self, barkley, 0-54, high is poor, fv, <3 months fu) in the intervention groups was

8.23 lower (11.86 lower to 4.61 lower)

ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months PT)

104

(2 studies)

8-12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self, barkley, 0-27, high is poor, fv, <3 months pt) in the control groups was 7.86

The mean ADHD symptoms (hyperactivity, self, barkley, 0-27, high is poor, fv, <3 months pt) in the intervention groups was

1.36 lower (3.46 lower to 0.74 higher)

ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months FU)

(2 studies)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self, barkley, 0-27, high is poor, fv, <3 months fu) in the control groups was

8.16

The mean ADHD symptoms (hyperactivity, self, barkley, 0-27, high is poor, fv, <3 months fu) in the intervention groups was

2.97 lower (4.90 to 1.03 lower)

ADHD symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months PT)

104

(2 studies)

8-12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self, barkley, 0-27, high is poor, fv, <3 months pt) in the control groups was 13.71

The mean ADHD symptoms (inattention, self, barkley, 0-27, high is poor, fv, <3 months pt) in the intervention groups was

3.63 lower (5.55 to 1.71 lower)

ADHD symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months FU)

(2 studies)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self, barkley, 0-27, high is poor, fv, <3 months fu) in the control groups was 14.19

The mean ADHD symptoms (inattention, self, barkley, 0-27, high is poor, fv, <3 months fu) in the intervention groups was

5.26 lower (7.60 to 2.93 lower)

Responders by CGI (two point change in CGI-S, >3 months PT)

(1 study)

15 weeks

LOW^a^,^b

due to risk of bias, imprecision

RR 4.22

(1.08 to 16.45)

Moderate

133 per 1000

428 more per 1000

(from 11 more to 1000 more)

Emotional dysregulation (observer, HAM-D, 0-53, high is worse, FV, >3 months PT)

(1 study)

15 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean emotional dysregulation (observer, ham-d, 0-53, high is worse, fv, >3 months pt) in the control groups was

The mean emotional dysregulation (observer, ham-d, 0-53, high is worse, fv, >3 months pt) in the intervention groups was

5.56 lower

(9.71 to 1.41 lower)

Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months PT)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean emotional dysregulation (bdi, 0-64, high is worse, fv, <3 months PT) in the control groups was

The mean emotional dysregulation (bdi, 0-64, high is worse, fv, <3 months pt) in the intervention groups was

5.62 lower

(9.85 to 1.39 lower)

Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months FU)

(1 study)

12 weeks

LOW^a

due to risk of bias

The mean emotional dysregulation (bdi, 0-64, high is worse, fv, <3 months fu) in the control groups was

13.14

The mean emotional dysregulation (bdi, 0-64, high is worse, fv, <3 months fu) in the intervention groups was

8.10 lower

(11.72 to 4.43 lower)

Behaviour/function (Self rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months PT)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (rate antisocial scale, unclear range, high is worse, fv, <3 months pt) in the control groups was

10.29

The mean behaviour/function (rate antisocial scale, unclear range, high is worse, fv, <3 months pt) in the intervention groups was

1.05 lower

(1.99 to 0.11 lower)

Behaviour/function (Self rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months FU)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean behaviour/function (rate antisocial scale, unclear range, high is worse, fv, <3 months fu) in the control groups was

11.19

The mean behaviour/function (rate antisocial scale, unclear range, high is worse, fv, <3 months fu) in the intervention groups was

2.43 lower

(3.97 to 0.89 lower)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 33Clinical evidence summary: mixed medication + CBT/DBT versus mixed medication + NSST

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Medication + NSST

Risk difference with Medication + CBT/DBT (95% CI)

QoL (QLESQ, unclear scale, high is better, FV, >3 months PT)

(1 study)

12 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean qol (qlesq, unclear scale, high is better, fv, >3 months pt) in the control groups was

207.4

The mean qol (qlesq, unclear scale, high is better, fv, >3 months pt) in the intervention groups was

33.10 higher

(35.83 lower to 102.03 higher)

ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months PT)

110

(2 studies)

12-15 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

Control group results unavailable

The mean ADHD symptoms (total, self, ADHD-rs, high is worse, fv, 0-54, >3 months pt) in the intervention groups was

0.33 standard deviations lower

(0.7 lower to 0.05 higher)

ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months FU)

(1 study)

52 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, self, ADHD-rs, high is worse, fv, 0-54, >3 months fu) in the control groups was

16.97

The mean ADHD symptoms (total, self, ADHD-rs, high is worse, fv, 0-54, >3 months fu) in the intervention groups was

3.58 lower

(6.34 to 0.82 lower)

ADHD symptoms (hyperactivity, self, CAARS, high is worse, FV, 0-27, >3 months PT)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, self, caars, high is worse, fv, 0-27, >3 months pt) in the control groups was

13.88

The mean ADHD symptoms (hyperactivity, self, caars, high is worse, fv, 0-27, >3 months pt) in the intervention groups was

1.72 higher

(4.41 lower to 7.85 higher)

ADHD symptoms (inattention, self, CAARS, high is worse, FV, 0-27, >3 months PT)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, self, caars, high is worse, fv, 0-27, >3 months pt) in the control groups was

18.58

The mean ADHD symptoms (inattention, self, caars, high is worse, fv, 0-27, >3 months pt) in the intervention groups was

1.35 higher

(4.62 lower to 7.32 higher)

CGI-I responders (>3 months PT)

(1 study)

15 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

RR 2.21

(1.17 to 4.16)

Moderate

243 per 1000

294 more per 1000

(from 41 more to 768 more)

Emotional dysregulation (Self, BDI, 0-63, high is worse, FV, >3 months PT)

(1 study)

12 weeks

VERY LOW^a^,^b

due to risk of bias, imprecision

The mean emotional dysregulation (bdi, 0-63, high is worse, fv, >3 months pt) in the control groups was

13.64

The mean emotional dysregulation (bdi, 0-63, high is worse, fv, >3 months pt) in the intervention groups was

1.24 lower

(9.37 lower to 6.89 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 34Clinical evidence summary: Stimulants + CBT/DBT compared to NSST alone

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with NSST alone

Risk difference with Stimulants + CBT/DBT (95% CI)

ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

206

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the control groups was

The mean ADHD symptoms (total, self, caars, high is worse, fv, >3 months pt) in the intervention groups was

2.70 lower

(4.45 to 0.95 lower)

ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

206

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (total, observer, caars, high is worse, fv, >3 months pt) in the control groups was

17.5

The mean ADHD symptoms (total, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

2.60 lower

(4.49 to 0.71 lower)

ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

206

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the control groups was

15.2

The mean ADHD symptoms (hyperactivity, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

2.20 lower

(4.02 to 0.38 lower)

ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

206

(1 study)

52 weeks

LOW^a^,^b

due to risk of bias, imprecision

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the control groups was

17.5

The mean ADHD symptoms (inattention, observer, caars, high is worse, fv, >3 months pt) in the intervention groups was

2.50 lower

(4.32 to 0.68 lower)

Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

206

(1 study)

52 weeks

MODERATE^a

due to risk of bias

The mean emotional dysregulation (bdi, 0-63, high is poor, fv, >3 months pt) in the control groups was

10.1

The mean emotional dysregulation (bdi, 0-63, high is poor, fv, >3 months pt) in the intervention groups was

1.20 lower

(3.30 lower to 0.90 higher)

(a): Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

(b): Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs.

Table 35Health economic evidence profile: CBT added to medication versus medication alone in adults on medication but with clinically significant symptoms

Study

Applicability

Limitations

Other comments

Incremental cost

Incremental effects

Costeffectiveness

Uncertainty

CG72 Original analysis⁴⁵ [UK]

Directly applicable^(a)

Potentially serious limitations^(b)

Decision tree model with 1 year time horizon comparing adding 15 weeks of individual CBT on top of medication versus medication alone (in adults with ADHD who have been stabilised on medication and continue to show clinically significant symptoms).

Clinical effectiveness from a single RCT (Safren 2005⁵¹).

Includes only CBT costs.

£1,122

0.016

£65,279

No probabilistic analysis.

Various one way sensitivity analyses and threshold analyses tested.

The ICER stayed above the threshold under all scenarios but group CBT. However this varied wildly (from £13,566 to £535,556 per QALY in the various alternative hypotheses tested).

: Abbreviations: ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life years; RCT: randomised controlled trial; CBT: Cognitive behavioural Therapy.

(a): UK NHS perspective. Directly relevant comparisons to the question.

(b): Based only on one study with 31 participants. Includes only intervention costs – no other cost savings utilities from a study comparing two doses of atomoxetine and may not reflect utilities associated with behavioural therapy. Extrapolation of effect over 1 year time horizon. Assuming tin the sensitivity analysis that group CBT is as effective as individual CBT. No probabilistic sensitivity analysis.

Table 36Health economic evidence profile: combination of Atomoxetine + behavioural therapy versus atomoxetine versus behavioural therapy, in children

Study

Applicability

Limitations

Other comments

Incremental cost

Incremental effects (QALYs)

Costeffectiveness

Uncertainty

Original NICE analysis [UK]

Directly applicable^(a)

Potentially serious limitations^(b)

Decision tree model with 1 year time horizon comparing; atomoxetine combined with behavioural therapy, behavioural therapy, and atomoxetine, in children.

Clinical effectiveness is from 3 studies included in the clinical review (with trial periods of around 10 weeks) that had relevant dichotomous outcomes. Includes adverse events from ATX.

Cost included are the intervention costs, including staff costs for monitoring drug and staff resource use also used to represent costs associated with response/no response. Utilities associated with response/no response included and combined with costs to derive cost per QALY.

ATX versus BT = £732

Combination versus ATX = £227

ATX versus BT = 0.017

Combination versus ATX = 0.004

ATX versus BT = £44,175

Combination versus ATX = £56,219

Behavioural therapy most cost effective.

Net benefits:

BT = £14,589

ATX = £14,197

Combination = £14,051

Base case results were probabilistic based on 10,000 simulations.

Various one way sensitivity analyses were tested;

-: assuming response from behavioural therapy diminishes after treatment ends; BT still most cost effective.

-: BT on an individual basis; ATX most cost effective.

-: Using alternative source of utility data; BT still most cost effective.

: Abbreviations: ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life years; RCT: BT: behavioural therapy; ATX: Atomoxetine

(a): UK NHS perspective. Directly relevant comparisons to the question. Uses EQ-5D.

(b): Based only on three trials, with varying intensity of particularly behavioural therapy interventions. No assumptions made about further sequences of treatments which may be underestimating QALYs/costs. Extrapolation of effect for behavioural therapy. No deterioration of the condition or impact of effect modelled over time.

Table 37Health economic evidence profile: Methylphenidate + self-help behavioural therapy versus methylphenidate, in children on methylphenidate but with functional impairment

Study

Applicability

Limitations

Other comments

Incremental cost

Incremental effects (QALYs)

Costeffectiveness

Uncertainty

Original NICE analysis [UK]

Directly applicable^(a)

Potentially serious limitations^(b)

Decision tree model with 1 year time horizon comparing; adding telephone assisted self-help behavioural therapy to MPH versus staying on MPH alone (in a population of children who are partial responders to the MPH).

Clinical effectiveness is from a single study (trial length of 12 months) that had relevant dichotomous outcomes.

Costs included are only the costs of the behavioural therapy. Utilities associated with response/no response included and combined with costs to derive cost per QALY.

£868

0.0076

£114,803

Base case results were probabilistic based on 10,000 simulations.

Various threshold and sensitivity analyses (SA’s) were tested;

-: Threshold analyses; cost of intervention would have to be below £151 to make intervention cost effective, equating to 2-3 sessions. Incremental QALY would have to be 0.0434. Time horizon Would have to be around 3 years.

-: Assuming effect increases linearly to 6 months as the phone calls are more intense up until that point, and stays at that level until 12 months (ICER = £76,407).

-: 2-way SA varying baseline response probability and intervention response RR showed that no level of combination of baseline risk and RR would make the intervention cost effective.

-: 2-way SA varying time horizon and utility gain showed that intervention can be cost effective if time horizon is generally over 3 years.

-: Using alternative sources of utility data; ICER still remained high.

: Abbreviations: ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life years; RR: relative risk; BT: behavioural therapy; MPH: methylphenidate (a) UK NHS perspective. Directly relevant comparisons to the question. Uses EQ-5D.

(a): UK NHS perspective. Directly relevant comparisons to the question. Uses EQ-5D.

(b): Effect based only on one study. No assumptions made about other treatments or impact of behavioural therapy on the underlying resource use. No deterioration of the condition or impact of effect modelled over time. Effect felt to be underestimated.

Table 38Health economic evidence profile: Medication + CBT versus medication, in adolescents on medication but with clinically significant symptoms

Study

Applicability

Limitations

Other comments

Incremental cost

Incremental effects

Cost-effectiveness

Uncertainty

Original NICE analysis [UK]

Directly applicable^(a)

Potentially serious limitations^(b)

Decision tree model with 1 year time horizon comparing; adding individual CBT on to medication versus staying on medication alone (in a population of adolescents partially responsive to medication).

Clinical effectiveness is from a single study (trial length of 4 months) that had relevant dichotomous outcomes.

Costs included are only the costs of the CBT. Utilities associated with response/no response included and combined with costs to derive cost per QALY.

£1,164

0.0188

£62,007

Base case results were probabilistic based on 10,000 simulations.

Various threshold and sensitivity analyses (SA’s) were tested;

-: Cost of intervention would have to be below £375 to make the intervention cost effective. Incremental QALY would have to be 0.0582. Time horizon would have to be 2.8 years.

-: Assuming the added effect of CBT diminishes after treatment ends (ICER = £105,192).

-: 2-way SA varying baseline response probability and intervention response RR showed that no level of combination of baseline risk and RR would make the intervention cost effective.

-: 2-way SA varying time horizon and utility gain showed that intervention can be cost effective with a longer time horizon of 2-4 years depending on utilty gain.

-: Using alternative sources of utility data; ICER still remained high.

: Abbreviations: ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life years; CBT: Cognitive behavioural Therapy; RR: relative risk

(a): UK NHS perspective. Directly relevant comparisons to the question. Used EQ-5D.

(b): Effect based only on one study. No assumptions made about other treatments or impact of behavioural therapy on the underlying resource use. No deterioration of the condition or impact of effect modelled over time. Effect felt to be underestimated.

Table 39UK costs of ADHD drugs for children

Drug	Daily dose (or unit or total)	Cost (per unit)	Cost – monthly	Cost – annual	Source
Methylphenidate hydrochloride
Methylphenidate immediate release	Low dose: 10mg per day	5mg tablet (pack of 30) = £3.03	£6.14	£73.73	Dose: BNF Cost: BNF (DT price)
Methylphenidate immediate release	High dose: 60mg per day	20mg tablet (pack of 30) = £10.92	£33.22	£398.58	Dose: BNF Cost: BNF (DT price)
Modified release tablet	Low dose: 18mg per day	18mg tablet (pack of 30) = £31.19	£31.62	£379.48	Dose: BNF Cost: BNF (DT price)
Modified release tablet	High dose: 54mg per day	54mg tablet (pack of 30) = £60.48	£61.32	£735.84	Dose: BNF Cost: BNF (DT price)
Modified release capsule	Low dose: 20mg per day	20mg capsule (pack of 30) = £30.00	£30.42	£365.00	Dose: BNF Cost: BNF (DT price)
Modified release capsule	High dose: 60 mg per day	60mg capsule (pack of 30) = £67.32	£68.26	£819.06	Dose: BNF Cost: BNF (NHS indicative price)^(a)
Atomoxetine
Capsule	Low dose: 40 mg per day	40mg capsule (pack of 28) = £53.09	£57.67	£692.07	Dose: BNF Cost: BNF (DT price)
Capsule	High dose: 100 mg per day	100mg capsule (pack of 28) = £70.79	£76.90	£922.80	Dose: BNF Cost: BNF (DT price)
Oral solution	High dose: 100 mg per day	4mg/1ml oral solution (300 ml) = £85	£215.45	£2,585.42	Dose: Using equivalent high tablet dose Cost: BNF (DT price)
Dexamfetamine
Tablet	Low dose: 5mg per day	5mg tablet (pack of 28) = £21.53	£23.39	£280.66	Dose: BNF Cost: BNF (DT price)
Tablet	High dose: 20mg per day	10mg tablet (pack of 30) = £39.78	£80.67	£967.98	Dose: BNF Cost: BNF (DT price)
Oral solution	High dose: 20mg per day	5mg/5ml oral solution (500ml) = £114.49	£139.30	£1,671.55	Dose: Using equivalent high tablet dose Cost: BNF (DT price)
Lisdexamfetamine
	Low dose: 20mg per day^(b)	20mg capsule (pack of 28) = £54.62	£59.33	£712.01	Dose: guideline committee Cost: BNF (DT price)
	Low dose: 30mg per day	30mg capsule (pack of 28) = £58.24	£63.27	£759.20	Dose: BNF Cost: BNF (DT price)
	High dose: 70mg per day	70mg capsule (pack of 28) = £83.16	£90.34	£1,084.05	Dose: BNF Cost: BNF (DT price)
Other drugs^(c)
Guanfacine hydrochloride (modified release)	4mg per day	4mg tablet (pack of 28) = £76.16	£82.73	£992.80	Dose: Clinical review Cost: BNF (NHS indicative price)
Clonidine hydrochloride	400 micrograms per day^(d)	100 microgram tablet (pack of 112) = £8.04	£8.73	£104.81	Dose: Clinical review Cost: BNF (DT price)
Risperidone	2mg per day	1mg tablet (pack of 20) = £0.80	£2.43	£29.20	Dose: Clinical review Cost: BNF (DT price)
Amantadine hydrochloride	150mg per day	100mg tablet (pack of 56) = £41.00	£33.40	£400.85	Dose: Clinical review Cost: BNF (DT price)
Melatonin (modified release)	6mg per day	2mg tablet (pack of 30) = £15.39	£46.81	£561.74	Dose: Clinical review Cost: BNF (DT price)
Bupropion hydrochloride (modified release)	150mg per day	150mg tablet (pack of 60) = £41.76	£21.17	£254.04	Dose: Clinical review Cost: BNF (DT price)
Modafinil	300mg per day	100mg tablet (pack of 30) = £5.88	£17.89	£214.62	Dose: Clinical review Cost: BNF (DT price)
Buspirone hydrochloride	30mg per day	10mg tablet (pack of 30) = £4.63	£14.08	£169.00	Dose: Clinical review Cost: BNF (DT price)
Aripiprazole	20mg per day	10mg tablet (pack of 28) = £2.77	£6.02	£72.22	Dose: Clinical review Cost: BNF (DT price)
Venlafaxine hydrochloride	75mg per day	37.5mg tablet (pack of 56) = £2.04	£2.22	£26.59	Dose: Clinical review Cost: BNF (DT price)

: Source: BNF, October 2017.

(a): No drug tariff price available for the 60mg.

(b): A dose of 20mg is demonstrated here as committee opinion was that this is a dose that would be used in children, even though it is below the BNF starting dose.

(c): Guanfacine is the only drug from this list licensed for ADHD. It is less commonly used and is a newer drug so one example dose within the licensed range is demonstrated here. The doses of the other drugs below guanfacine were taken from the clinical review as there was no information in the BNF about doses for this condition.

(d): Based on a dose from a trial of 8micrograms per kg and assuming a 50kg child (a conservative estimate of weight)

Table 40UK costs of ADHD drugs for adults

Drug	Daily dose (or unit or total)	Cost (per unit)	Cost – monthly	Cost – annual	Source of dose
Methylphenidate hydrochloride
Methylphenidate immediate release	Low dose: 20mg per day	10mg tablet (pack of 30) = £5.49	£11.13	£133.59	Dose: BNF Cost: BNF (DT price)
Methylphenidate immediate release	High dose: 100mg per day	As above	£55.36	£664.30	Dose: BNF Cost: BNF (DT price)
Modified release tablet	Low dose: 36mg per day	36mg tablet (pack of 30) = £42.45	£43.04	£516.48	Dose: BNF Cost: BNF (DT price)
Modified release tablet	High dose: 108mg per day	54mg tablet^(a) (pack of 30) = £60.48	£122.64	£1,471.68	Dose: BNF Cost: BNF (DT price)
Modified release capsule	Low dose: 20mg per day	20mg capsule (pack of 30) = £30.00	£30.42	£365.00	Dose: BNF Cost: BNF (DT price)
Modified release capsule	High dose: 100mg per day	50mg capsule (pack of 30) = £62.52	£126.78	£1,521.32	Dose: BNF Cost: BNF (NHS indicative price)^(a)
Atomoxetine
	Low dose: 40 mg per day	40mg tablet (pack of 28) = £53.09	£57.67	£692.07	Dose: BNF Cost: BNF (DT price)
	High dose: 100 mg per day	100mg tablet (pack of 28) = £70.79	£92.28	£1,107.36	Dose: BNF Cost: BNF (DT price)
Lisdexamfetamine dimesylate
	Low dose: 30 mg per day	30mg tablet (pack of 28) = £58.24	£63.27	£759.20	Dose: BNF Cost: BNF (DT price)
	High dose: 70 mg per day	70mg tablet (pack of 28) = £83.16	£90.34	£1,084.05	Dose: BNF Cost: BNF (DT price)
Dexamfetamine sulfate
	Low dose: 20mg per day	10mg tablet (pack of 30) = £39.78	£80.67	£967.98	Dose: BNF Cost: BNF (DT price)
	High dose: 60mg per day	20mg tablet (pack of 30) = £79.56	£161.33	£1,935.96	Dose: BNF Cost: BNF (NHS indicative price)^(a)
Other drugs
Guanfacine hydrochloride (modified release)	4mg per day	4mg tablet (pack of 28) = £76.16	£82.73	£992.80	Dose: Estimate based on children’s dose Cost: BNF (NHS indicative price)
Bupropion hydrochloride (modified release)	300 mg per day	150mg tablet (pack of 60) = £41.76	£42.34	£508.08	Dose: Clinical review Cost: BNF (DT price)
Reboxetine (Edronax)	8mg per day	4mg tablet (pack of 60) = £18.91	£19.17	£230.07	Dose: Clinical review Cost: BNF (DT price)
Venlafaxine hydrochloride	225 mg per day	37.5mg tablet (pack of 56) = £2.04	£6.65	£79.78	Dose: Clinical review Cost: BNF (DT price)

: Source: BNF, October 2017.

(a): No BNF drug tariff price for this dose yet.

Table 41Staff costs associated with selecting and monitoring medication treatment

Staff	Costs	Source
Psychiatric Consultant	£106 per hour	PSSRU 2016
Band 5 nurse	£36 per hour	PSSRU 2016

Table 42Staff costs associated with behavioural therapy

Staff

Costs

Source

Clinical psychologist

(Band 8a, clinical psychologist principal (community based))

£62 per hour

PSSRU 2016

Band 4 assistant

£30 per hour

PSSRU 2016

Table 43Published PSSRU costs on cognitive behavioural treatments

Intervention

Details

Costs

Source

Cognitive Behavioural Therapy for adolescents (individual).^(a)

Length of contact; 55 minutes (average duration of sessions)

£97 per CBT session

PSSRU 2016

Mindfulness based cognitive therapy – group based intervention for adults.^(b)

Therapy sessions lasted 2 hours with 12 people attending each session.

£52 per hour of non-direct contact,

£86 per hour of direct contact,

£173 per session,

£14 per service user (=£173/12 people)

PSSRU 2016

(a): This cost is based on costs estimated for a randomised controlled trial of interventions for adolescents with depression. The setting was two Child and Mental Health Services (CAMHS) teams in secondary care where CBT was delivered.

(b): Mindfulness-based cognitive therapy (MBCT) is a manualised skills training programme designed to enable patients to learn skills that prevent the recurrence of depression. It is derived from mindfulness-based stress reduction, a programme with proven efficacy in ameliorating distress in people suffering chronic disease. To provide the unit costs of this service, we have drawn on information provided by Kuyken et al. (2008) which was based on data from three mindfulness-based cognitive therapy therapists who took part in the study. There were 12 individuals in each group.

Table 44Review protocol: Combined pharmacological and non-pharmacological treatment

Field	Content
Review question	What is the most clinically and cost-effective combination of pharmacological and non-pharmacological treatment for people with ADHD?
Type of review question	Intervention A review of health economic evidence related to the same review question was conducted in parallel with this review. For details see the health economic review protocol for this NICE guideline.
Objective of the review	To identify the most clinically and cost-effective combination of pharmacological and/or non-pharmacological treatment for people with ADHD
Eligibility criteria – population / disease / condition / issue / domain	Children, young people and adults with ADHD. Stratified by age: <5 years 5 to 18 years >18 years Note that papers will not be included if their population has been selected exclusively on the basis of response or tolerance to an intervention under investigation
Eligibility criteria – interventions	Pharmacological treatments (mixed, stimulants (including methylphenidate, dexamfetamine and lisdexamfetamine), atomoxetine) Non-pharmacological treatments (parent/family/carer training, CBT/DBT, psychoeducation, attention/memory/cognitive training, neurofeedback, relaxation techniques, organisational skills/school or workplace targeted interventions, exercise, outdoor activities Combinations of pharmacological and non-pharmacological treatments
Eligibility criteria – comparator(s) / control or reference (gold) standard	Any pharmacological treatment versus any non-pharmacological treatment Any combined treatment versus any pharmacological/non-pharmacological treatment alone Any combined treatment versus any other combined treatment Any combined treatment versus usual care
Outcomes and prioritisation	Outcomes to be extracted for end of intervention and latest follow-up if both available. Outcomes to be stratified into short term (up to 3 months follow-up) and long term (>3 months follow-up). Where multiple timepoints are reported within each definition, the longest timepoint only will be extracted. Critical: Quality of life [continuous] ADHD symptoms (total; parent/partner/carer) [continuous] ADHD symptoms (total; teacher) [continuous] ADHD symptoms (total; self-rated except for children <13) [continuous] ADHD symptoms (total; investigator) [continuous] ADHD symptoms (inattention; parent/partner/carer) [continuous] ADHD symptoms (inattention; teacher) [continuous] ADHD symptoms (inattention; self- except for children <13) [continuous] ADHD symptoms (inattention; investigator) [continuous] ADHD symptoms (hyperactivity/impulsivity; parent/partner/carer) [continuous] ADHD symptoms (hyperactivity/impulsivity; teacher) [continuous] ADHD symptoms (hyperactivity/impulsivity; self-rated except for children <13) [continuous] ADHD symptoms (hyperactivity/impulsivity; investigator) [continuous] Clinical Global Impressions scale – improved (much improved or very much improved) [dichotomous] Important: Discontinuation due to intervention (for example perceived lack of efficacy, adverse events) [dichotomous] Serious adverse events [dichotomous] Behavioural measures [continuous] Emotional dysregulation [continuous] Academic outcomes (literacy, numeracy or combined) [continuous]
Eligibility criteria – study design	RCTs, systematic reviews of RCTs
Other inclusion exclusion criteria	Exclusions: Crossover trials with inappropriate washout period Pharmacological treatment received <2 weeks Trials that only include responders to treatment under investigation ADHD diagnosis made not using DSM-III/ICD-910 or later versions of these Studies published after the publication of DSM-III (1978) will be included if describe their population as having a formal diagnosis of ADHD Studies evaluating treatments for ADHD in a population of people with ASD will be included if no formal diagnosis of ADHD has been made, but evidence of moderate to severe symptoms of hyperactivity, impulsivity, and/or inattention is demonstrated according to validated symptom questionnaires)
Proposed sensitivity / subgroup analysis, or meta-regression	Previous treatment and response of population will be used for subgroup analysis in the case of heterogeneity. Studies including dietary interventions will only be included where dietary interventions are combined with pharmacological treatment and compared to an intervention other than dietary interventions alone. Dichotomous data for ADHD symptom scales other than CGI-I, will only be extracted if continuous data is not available and the definition of improved used is consistent with at least a 20% reduction in symptoms from baseline. Appraisal of methodological quality: The methodological quality of each study will be assessed using NICE checklists and GRADE. Stratification: Age Pre-schoolers (under 6 years) Children and young people (6-17 years) Adults (>18 years) Subgroups: Comorbidities: Intellectual disability (</>70 IQ) Autism spectrum (including Asperger’s, PDD, NOS/atypical) Neurological disorder (epilepsy) Affective disorder (depression and anxiety all combined) Tic disorder and Tourette’s Personality disorder Addiction Age: Adults (18-65 years) Older adults (>65 years) Severity Mild, moderate and severe Population Previous use of interventions, degree of response Secure estate Other adults Dose Low Medium High Method of titration Fixed dosage Titrate to optimal dose Diagnostic method DSM-III+ ICD-10 Country UK, Europe, USA, Japan. Other countries to allocate as appropriate. For non-pharmacological interventions: Mode of delivery Self-help Facilitated remotely (i.e. online, telephone support) Face to face (1 on 1) Face to face (group interventions) Place of delivery In educational setting (children or young adults) Home setting Clinic setting Secure estate
Selection process – duplicate screening / selection / analysis	A sample of at least 10% of the abstract lists were double-sifted by a senior research fellow and discrepancies rectified, with committee input where consensus could not be reached, for more information please see the separate Methods report for this guideline.
Data management (software)	Databases: Medline, Embase, the Cochrane Library, Psychinfo
Information sources – databases and dates	Clinical search databases to be used: Medline, Embase, Cochrane Library,PsycINFO Date: From October 2007 Health economics search databases to be used: Medline, Embase, NHSEED, HTA Date: Medline, Embase from 2014 NHSEED, HTA – from 2008 Language: Restrict to English only Supplementary search techniques: backward citation searching Key papers: Not known
Identify if an update	Not an update
Author contacts	https://www.nice.org.uk/guidance/cg72
Highlight if amendment to previous protocol	Not an amendment
Search strategy – for one database	For details please see appendix B
Data collection process – forms / duplicate	A standardised evidence table format will be used, and published as appendix D of the evidence report.
Data items – define all variables to be collected	For details please see evidence tables in Appendix D (clinical evidence tables) or H (health economic evidence tables).
Methods for assessing bias at outcome / study level	Standard study checklists were used to critically appraise individual studies. For details please see section 6.2 of Developing NICE guidelines: the manual The risk of bias across all available evidence was evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group http://www.gradeworkinggroup.org/
Criteria for quantitative synthesis	For details please see section 6.4 of Developing NICE guidelines: the manual.
Methods for quantitative analysis – combining studies and exploring (in)consistency	For details please see the separate Methods report for this guideline.
Meta-bias assessment – publication bias, selective reporting bias	For details please see section 6.2 of Developing NICE guidelines: the manual.
Confidence in cumulative evidence	For details please see sections 6.4 and 9.1 of Developing NICE guidelines: the manual and the methods report of this guideline
Rationale / context – what is known	For details please see the introduction to the evidence review.
Describe contributions of authors and guarantor	A multidisciplinary committee developed the evidence review. The committee was convened by the National Guideline Centre (NGC) and chaired by Gillian Baird in line with section 3 of Developing NICE guidelines: the manual and the methods report of this guideline. Staff from NGC undertook systematic literature searches, critically appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the evidence review in collaboration with the committee. For details please see Developing NICE guidelines: the manual.
Sources of funding / support	NGC is funded by NICE and hosted by the Royal College of Physicians.
Name of sponsor	NGC is funded by NICE and hosted by the Royal College of Physicians.
Roles of sponsor	NICE funds NGC to develop guidelines for those working in the NHS, public health and social care in England.
PROSPERO registration number	Not registered

Table 45Health economic review protocol

Review question	All questions – health economic evidence
Objectives	To identify health economic studies relevant to any of the review questions.
Search criteria	Populations, interventions and comparators must be as specified in the clinical review protocols in appendix A above. Studies must be of a relevant health economic study design (cost–utility analysis, cost-effectiveness analysis, cost–benefit analysis, cost–consequences analysis, comparative cost analysis). Studies must not be a letter, editorial or commentary, or a review of health economic evaluations. (Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will then be ordered.) Unpublished reports will not be considered unless submitted as part of a call for evidence. Studies must be in English.
Search strategy	A health economic study search will be undertaken using population-specific terms and a health economic study filter – see appendix B. For questions being updated, the search will be run from December 2007, which was the cut-off date for the searches conducted for NICE guideline CG72
Review strategy	Studies not meeting any of the search criteria above will be excluded. Studies published before 2001, abstract-only studies and studies from non-OECD countries or the USA will also be excluded. Studies published after 2001 that were included in the previous guideline will be reassessed for inclusion and may be included or selectively excluded based on their relevance to the questions covered in this update and whether more applicable evidence is also identified. Each remaining study will be assessed for applicability and methodological limitations using the NICE economic evaluation checklist which can be found in appendix H of Developing NICE guidelines: the manual (2014).⁴⁶ Inclusion and exclusion criteria If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’ then it will be included in the guideline. A health economic evidence table will be completed and it will be included in the health economic evidence profile. If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’ then it will usually be excluded from the guideline. If it is excluded then a health economic evidence table will not be completed and it will not be included in the health economic evidence profile. If a study is rated as ‘Partially applicable’, with ‘Potentially serious limitations’ or both then there is discretion over whether it should be included. Where there is discretion The health economist will make a decision based on the relative applicability and quality of the available evidence for that question, in discussion with the guideline committee if required. The ultimate aim is to include health economic studies that are helpful for decision-making in the context of the guideline and the current NHS setting. If several studies are considered of sufficiently high applicability and methodological quality that they could all be included, then the health economist, in discussion with the committee if required, may decide to include only the most applicable studies and to selectively exclude the remaining studies. All studies excluded on the basis of applicability or methodological limitations will be listed with explanation as excluded health economic studies in appendix I. The health economist will be guided by the following hierarchies. Setting: UK NHS (most applicable). OECD countries with predominantly public health insurance systems (for example, France, Germany, Sweden). OECD countries with predominantly private health insurance systems (for example, Switzerland). Studies set in non-OECD countries or in the USA will be excluded before being assessed for applicability and methodological limitations. Health economic study type: Cost–utility analysis (most applicable). Other type of full economic evaluation (cost–benefit analysis, cost-effectiveness analysis, cost–consequences analysis). Comparative cost analysis. Non-comparative cost analyses including cost-of-illness studies will be excluded before being assessed for applicability and methodological limitations. Year of analysis: The more recent the study, the more applicable it will be. Studies published in 2001 or later (including any such studies included in the previous guideline) but that depend on unit costs and resource data entirely or predominantly from before 2001 will be rated as ‘Not applicable’. Studies published before 2001 (including any such studies included in the previous guideline) will be excluded before being assessed for applicability and methodological limitations. Quality and relevance of effectiveness data used in the health economic analysis: The more closely the clinical effectiveness data used in the health economic analysis match with the outcomes of the studies included in the clinical review the more useful the analysis will be for decision-making in the guideline. Economic evaluations that are based on studies excluded from the clinical review will be excluded.

Table 46Database date parameters and filters used

Database	Dates searched	Search filter used
Medline (OVID)	01 October 2007 – 28 April 2017	Exclusions Randomised controlled trials Systematic review studies
Embase (OVID)	01 October 2007 – 28 April 2017	Exclusions Randomised controlled trials Systematic review studies
The Cochrane Library (Wiley)	Cochrane Reviews 2007 to 2017 Issue 4 of 12 CENTRAL 2007 to 2017 Issue 3 of 12 DARE and NHSEED 2007 to 2015 Issue 1 of 4 HTA 2007 to 2017 Issue 1 of 4	None
PsycINFO (ProQuest)	01 October 2007 – 28 April 2017	Exclusions Randomised controlled trials Systematic review studies

Medline (Ovid) search terms

1.	“attention deficit and disruptive behavior disorders”/ or attention deficit disorder with hyperactivity/
2.	((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)).ti.
3.	((attenti* or disrupt) adj3 disorder).ab.
4.	(ADHD or addh or ad hd or ad??hd).ti,ab.
5.	(attenti* adj3 deficit*).ti,ab.
6.	(((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd).ti,ab.
7.	(minimal brain adj2 (dysfunct* or disorder*)).ti,ab.
8.	or/1-7
9.	exp Child Development Disorders, Pervasive/
10.	(autistic or autism or asperger*).ti,ab.
11.	pervasive developmental disorder*.ti,ab.
12.	(asd or pdd or pdd-nos).ti,ab.
13.	or/9-12
14.	hyperkinesis/
15.	(hyperactiv* or inattent* or hyperkin* or hyper-kin*).ti,ab.
16.	14 or 15
17.	13 and 16
18.	8 or 17
19.	limit 18 to English language
20.	letter/
21.	editorial/
22.	news/
23.	exp historical article/
24.	Anecdotes as Topic/
25.	comment/
26.	case report/
27.	(letter or comment*).ti.
28.	or/20-27
29.	randomized controlled trial/ or random*.ti,ab.
30.	28 not 29
31.	animals/ not humans/
32.	Animals, Laboratory/
33.	exp animal experiment/
34.	exp animal model/
35.	exp Rodentia/
36.	(rat or rats or mouse or mice).ti.
37.	or/30-36
38.	19 not 37
39.	randomized controlled trial.pt.
40.	controlled clinical trial.pt.
41.	randomi#ed.ab.
42.	placebo.ab.
43.	drug therapy.fs.
44.	randomly.ab.
45.	trial.ab.
46.	groups.ab.
47.	or/39-46
48.	Clinical Trials as topic.sh.
49.	trial.ti.
50.	or/39-42,44,48-49
51.	Meta-Analysis/
52.	Meta-Analysis as Topic/
53.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
54.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
55.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
56.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
57.	(search* adj4 literature).ab.
58.	(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.
59.	cochrane.jw.
60.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
61.	or/51-60
62.	38 and (50 or 61)

Embase (Ovid) search terms

1.	attention deficit disorder/
2.	((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)).ti.
3.	((attenti* or disrupt) adj3 disorder).ab.
4.	(ADHD or addh or ad hd or ad??hd).ti,ab.
5.	(attenti* adj3 deficit*).ti,ab.
6.	(((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd).ti,ab.
7.	(minimal brain adj2 (dysfunct* or disorder*)).ti,ab.
8.	or/1-7
9.	exp autism/
10.	(autistic or autism or asperger*).ti,ab.
11.	pervasive developmental disorder*.ti,ab.
12.	(asd or pdd or pdd-nos).ti,ab.
13.	or/9-12
14.	hyperactivity/
15.	hyperkinesia/
16.	(hyperactiv* or inattent* or hyperkin* or hyper-kin*).ti,ab.
17.	or/14-16
18.	13 and 17
19.	8 or 18
20.	limit 19 to English language
21.	letter.pt. or letter/
22.	note.pt.
23.	editorial.pt.
24.	case report/ or case study/
25.	(letter or comment*).ti.
26.	or/21-25
27.	randomized controlled trial/ or random*.ti,ab.
28.	26 not 27
29.	animal/ not human/
30.	nonhuman/
31.	exp Animal Experiment/
32.	exp Experimental Animal/
33.	animal model/
34.	exp Rodent/
35.	(rat or rats or mouse or mice).ti.
36.	or/28-35
37.	20 not 36
38.	random*.ti,ab.
39.	factorial*.ti,ab.
40.	(crossover* or cross over*).ti,ab.
41.	((doubl* or singl) adj blind).ti,ab.
42.	(assign* or allocat* or volunteer* or placebo*).ti,ab.
43.	crossover procedure/
44.	single blind procedure/
45.	randomized controlled trial/
46.	double blind procedure/
47.	or/38-46
48.	systematic review/
49.	meta-analysis/
50.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
51.	((systematic or evidence) adj3 (review* or overview*)).ti,ab.
52.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
53.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
54.	(search* adj4 literature).ab.
55.	(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.
56.	cochrane.jw.
57.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
58.	or/48-57
59.	37 and (47 or 58)

Cochrane Library (Wiley) search terms

#1.	[mh ^“attention deficit and disruptive behavior disorders”]
#2.	[mh ^“attention deficit disorder with hyperactivity”]
#3.	((attenti* or disrupt) near/3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)):ti
#4.	((attenti* or disrupt) near/3 disorder):ab
#5.	(ADHD or addh or ad next hd or ad-hd):ti,ab
#6.	(attenti* near/3 deficit*):ti,ab
#7.	(((hyperkin* or (hyper near/1 kin)) near/1 (syndrome or disorder*)) or hkd):ti,ab
#8.	(minimal near/1 brain near/2 (dysfunct* or disorder*)):ti,ab
#9.	(or #1-#8)
#10.	[mh “Child Development Disorders, Pervasive”]
#11.	(autistic or autism or asperger*):ti,ab
#12.	(pervasive next developmental next disorder*):ti,ab
#13.	(asd or pdd or pdd-nos):ti,ab
#14.	(or #10-#13)
#15.	[mh ^hyperkinesis]
#16.	(hyperactiv* or inattent* or hyperkin* or hyper-kin*):ti,ab
#17.	#15 or #16
#18.	#14 and #17

PsycINFO (ProQuest) search terms

1.	(SU.EXACT.EXPLODE(“Attention Deficit Disorder”) OR TI((attenti* OR disrupt) NEAR/3 (adolescent OR adult* OR behav* OR child* OR class OR classes OR classroom* OR condition* OR difficult* OR disorder* OR learn* OR people OR person* OR poor OR problem* OR process* OR youngster)) OR AB((attenti OR disrupt) NEAR/3 disorder) OR TI,AB(ADHD OR addh OR ad-hd OR ad??hd) OR TI,AB(attenti* NEAR/3 deficit) OR TI,AB(((hyperkin OR (hyper-kin)) NEAR/1 (syndrome OR disorder)) OR hkd) OR TI,AB(minimal NEAR/1 brain NEAR/2 (dysfunct OR disorder))) OR ((SU.EXACT.EXPLODE(“Autism Spectrum Disorders”) or TI,AB(autistic or autism or asperger) or TI,AB(pervasive-developmental-disorder) or TI,AB(asd or pdd or pdd-nos)) AND (SU.EXACT(“Hyperkinesis”) or TI,AB(hyperactiv or inattent* or hyperkin* or hyper-kin*)))
2.	(su.exact.explode(“clinical trials”) OR ti,ab((clinical OR control) NEAR/3 trial) OR ti,ab((single* OR double* OR treble* OR triple) NEAR/5 (blind OR mask)) OR ti,ab(volunteer OR control-group OR controls) OR su.exact(“placebo”) OR ti,ab(placebo*))
3.	((SU.EXACT(“Literature Review”) or RTYPE(review) or ti(review) or me(literature review)) AND (ti,ab(systematic or evidence or methodol* or quantitative))) or (SU.EXACT(“Meta Analysis”) or ti,ab(meta-analys or metanalys* or metaanalys* or meta analys) or ti,ab((systematic or evidence or methodol* or quantitative) near/3 (review or overview)) or ti,ab((pool or combined or combining) near/2 (data or trials or studies or results)) or RTYPE(systematic or meta*) or ME(meta analysis or systematic review))
4.	1 AND (2 OR 3)
5.	Limit to English
6.	NOT (Dissertations & Theses AND Books)

Table 47Database date parameters and filters used

Database

Dates searched

Search filter used

Medline

2014 – 28 April 2017

Exclusions

Health economics

Embase

2014 – 28 April 2017

Exclusions

Health economics

Centre for Research and Dissemination (CRD)

HTA - 2008 – 28 April 2017

NHSEED - 2008 to March 2015

None

Medline (Ovid) search terms

1.	“attention deficit and disruptive behavior disorders”/ or attention deficit disorder with hyperactivity/
2.	((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)).ti.
3.	((attenti* or disrupt) adj3 disorder).ab.
4.	(ADHD or addh or ad hd or ad??hd).ti,ab.
5.	(attenti* adj3 deficit*).ti,ab.
6.	(((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd).ti,ab.
7.	(minimal brain adj2 (dysfunct* or disorder*)).ti,ab.
8.	or/1-7
9.	limit 8 to English language
10.	letter/
11.	editorial/
12.	news/
13.	exp historical article/
14.	Anecdotes as Topic/
15.	comment/
16.	case report/
17.	(letter or comment*).ti.
18.	or/10-17
19.	randomized controlled trial/ or random*.ti,ab.
20.	18 not 19
21.	animals/ not humans/
22.	Animals, Laboratory/
23.	exp animal experiment/
24.	exp animal model/
25.	exp Rodentia/
26.	(rat or rats or mouse or mice).ti.
27.	or/20-26
28.	9 not 27
29.	Economics/
30.	Value of life/
31.	exp “Costs and Cost Analysis”/
32.	exp Economics, Hospital/
33.	exp Economics, Medical/
34.	Economics, Nursing/
35.	Economics, Pharmaceutical/
36.	exp “Fees and Charges”/
37.	exp Budgets/
38.	budget*.ti,ab.
39.	cost*.ti.
40.	(economic* or pharmaco?economic*).ti.
41.	(price* or pricing*).ti,ab.
42.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
43.	(financ* or fee or fees).ti,ab.
44.	(value adj2 (money or monetary)).ti,ab.
45.	or/29-44
46.	exp models, economic/
47.	*Models, Theoretical/
48.	*Models, Organizational/
49.	markov chains/
50.	monte carlo method/
51.	exp Decision Theory/
52.	(markov* or monte carlo).ti,ab.
53.	econom* model*.ti,ab.
54.	(decision* adj2 (tree* or analy* or model*)).ti,ab.
55.	or/46-54
56.	28 and (45 or 55)

Embase (Ovid) search terms

1.	attention deficit disorder/
2.	((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)).ti.
3.	((attenti* or disrupt) adj3 disorder).ab.
4.	(ADHD or addh or ad hd or ad??hd).ti,ab.
5.	(attenti* adj3 deficit*).ti,ab.
6.	(((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd).ti,ab.
7.	(minimal brain adj2 (dysfunct* or disorder*)).ti,ab.
8.	or/1-7
9.	limit 8 to English language
10.	letter.pt. or letter/
11.	note.pt.
12.	editorial.pt.
13.	case report/ or case study/
14.	(letter or comment*).ti.
15.	or/10-14
16.	randomized controlled trial/ or random*.ti,ab.
17.	15 not 16
18.	animal/ not human/
19.	nonhuman/
20.	exp Animal Experiment/
21.	exp Experimental Animal/
22.	animal model/
23.	exp Rodent/
24.	(rat or rats or mouse or mice).ti.
25.	or/17-24
26.	9 not 25
27.	statistical model/
28.	exp economic aspect/
29.	27 and 28
30.	*theoretical model/
31.	*nonbiological model/
32.	stochastic model/
33.	decision theory/
34.	decision tree/
35.	monte carlo method/
36.	(markov* or monte carlo).ti,ab.
37.	econom* model*.ti,ab.
38.	(decision* adj2 (tree* or analy* or model*)).ti,ab.
39.	or/29-38
40.	*health economics/
41.	exp *economic evaluation/
42.	exp *health care cost/
43.	exp *fee/
44.	budget/
45.	funding/
46.	budget*.ti,ab.
47.	cost*.ti.
48.	(economic* or pharmaco?economic*).ti.
49.	(price* or pricing*).ti,ab.
50.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
51.	(financ* or fee or fees).ti,ab.
52.	(value adj2 (money or monetary)).ti,ab.
53.	or/40-52
54.	26 and (39 or 53)

NHS EED and HTA (CRD) search terms

#1.	MeSH DESCRIPTOR Attention Deficit and Disruptive Behavior Disorders
#2.	MeSH DESCRIPTOR Attention Deficit Disorder with Hyperactivity
#3.	(((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*))):TI
#4.	(((attenti* or disrupt) adj3 disorder))
#5.	((ADHD or addh or ad hd or ad??hd))
#6.	((attenti* adj3 deficit*))
#7.	((((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd))
#8.	((minimal brain adj2 (dysfunct* or disorder*)))
#9.	#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8
#10.	(#9) IN NHSEED, HTA

Table 48Database date parameters and filters used

Database

Dates searched

Search filters used

Medline

2008 – 28 September 2015

Exclusions

Quality of life

Embase

2008 – 28 September 2015

Exclusions

Quality of life

Medline (Ovid) search terms

1.	“attention deficit and disruptive behavior disorders”/ or attention deficit disorder with hyperactivity/
2.	((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)).ti.
3.	((attenti* or disrupt) adj3 disorder).ab.
4.	(ADHD or addh or ad hd or ad??hd).ti,ab.
5.	(attenti* adj3 deficit*).ti,ab.
6.	(((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd).ti,ab.
7.	(minimal brain adj2 (dysfunct* or disorder*)).ti,ab.
8.	or/1-7
9.	limit 8 to English language
10.	letter/
11.	editorial/
12.	news/
13.	exp historical article/
14.	Anecdotes as Topic/
15.	comment/
16.	case report/
17.	(letter or comment*).ti.
18.	or/10-17
19.	randomized controlled trial/ or random*.ti,ab.
20.	18 not 19
21.	animals/ not humans/
22.	Animals, Laboratory/
23.	exp animal experiment/
24.	exp animal model/
25.	exp Rodentia/
26.	(rat or rats or mouse or mice).ti.
27.	or/20-26
28.	9 not 27
29.	quality-adjusted life years/
30.	sickness impact profile/
31.	(quality adj2 (wellbeing or well being)).ti,ab.
32.	sickness impact profile.ti,ab.
33.	disability adjusted life.ti,ab.
34.	(qal* or qtime* or qwb* or daly*).ti,ab.
35.	(euroqol* or eq5d* or eq 5*).ti,ab.
36.	(qol* or hql* or hqol* or h qol* or hrqol* or hr qol*).ti,ab.
37.	(health utility* or utility score* or disutilit* or utility value*).ti,ab.
38.	(hui or hui1 or hui2 or hui3).ti,ab.
39.	(health* year* equivalent* or hye or hyes).ti,ab.
40.	discrete choice*.ti,ab.
41.	rosser.ti,ab.
42.	(willingness to pay or time tradeoff or time trade off or tto or standard gamble*).ti,ab.
43.	(sf36* or sf 36* or short form 36* or shortform 36* or shortform36*).ti,ab.
44.	(sf20 or sf 20 or short form 20 or shortform 20 or shortform20).ti,ab.
45.	(sf12* or sf 12* or short form 12* or shortform 12* or shortform12*).ti,ab.
46.	(sf8* or sf 8* or short form 8* or shortform 8* or shortform8*).ti,ab.
47.	(sf6* or sf 6* or short form 6* or shortform 6* or shortform6*).ti,ab.
48.	or/29-47
49.	28 and 48

Embase (Ovid) search terms

1.	attention deficit disorder/
2.	((attenti* or disrupt) adj3 (adolescent or adult* or behav* or child* or class or classes or classroom* or condition* or difficult* or disorder* or learn* or people or person* or poor or problem* or process* or youngster*)).ti.
3.	((attenti* or disrupt) adj3 disorder).ab.
4.	(ADHD or addh or ad hd or ad??hd).ti,ab.
5.	(attenti* adj3 deficit*).ti,ab.
6.	(((hyperkin* or hyper kin) adj1 (syndrome or disorder*)) or hkd).ti,ab.
7.	(minimal brain adj2 (dysfunct* or disorder*)).ti,ab.
8.	or/1-7
9.	limit 8 to English language
10.	letter.pt. or letter/
11.	note.pt.
12.	editorial.pt.
13.	case report/ or case study/
14.	(letter or comment*).ti.
15.	or/10-14
16.	randomized controlled trial/ or random*.ti,ab.
17.	15 not 16
18.	animal/ not human/
19.	nonhuman/
20.	exp Animal Experiment/
21.	exp Experimental Animal/
22.	animal model/
23.	exp Rodent/
24.	(rat or rats or mouse or mice).ti.
25.	or/17-24
26.	9 not 25
27.	quality adjusted life year/
28.	“quality of life index”/
29.	short form 12/ or short form 20/ or short form 36/ or short form 8/
30.	sickness impact profile/
31.	(quality adj2 (wellbeing or well being)).ti,ab.
32.	sickness impact profile.ti,ab.
33.	disability adjusted life.ti,ab.
34.	(qal* or qtime* or qwb* or daly*).ti,ab.
35.	(euroqol* or eq5d* or eq 5*).ti,ab.
36.	(qol* or hql* or hqol* or h qol* or hrqol* or hr qol*).ti,ab.
37.	(health utility* or utility score* or disutilit* or utility value*).ti,ab.
38.	(hui or hui1 or hui2 or hui3).ti,ab.
39.	(health* year* equivalent* or hye or hyes).ti,ab.
40.	discrete choice*.ti,ab.
41.	rosser.ti,ab.
42.	(willingness to pay or time tradeoff or time trade off or tto or standard gamble*).ti,ab.
43.	(sf36* or sf 36* or short form 36* or shortform 36* or shortform36*).ti,ab.
44.	(sf20 or sf 20 or short form 20 or shortform 20 or shortform20).ti,ab.
45.	(sf12* or sf 12* or short form 12* or shortform 12* or shortform12*).ti,ab.
46.	(sf8* or sf 8* or short form 8* or shortform 8* or shortform8*).ti,ab.
47.	(sf6* or sf 6* or short form 6* or shortform 6* or shortform6*).ti,ab.
48.	or/27-47
49.	26 and 48

Figure 1ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 2ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 3ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 4ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 5ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 6ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 7Responders by CGI-I (PT, <3 months)

Figure 8ADHD symptoms (hyperactivity, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 9ADHD symptoms (hyperactivity, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 10ADHD symptoms (inattention, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 11ADHD symptoms (inattention, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 12ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 13ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 14ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 15ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 16ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 17ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 18ADHD symptoms (hyperactivity, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 19ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 20ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 21ADHD symptoms (hyperactivity, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 22ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 23ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 24ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 25ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 26ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 27ADHD symptoms (inattention, parent, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 28ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 29ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 30ADHD symptoms (inattention, teacher, SWAN, 0-3, high is poor, FV, PT <3 months)

Figure 31ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 32ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 33ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 34Academic (general, self, 1-10, high is good, CS, PT <3 months)

Figure 35Academic (general, self, 1-10, high is good, PT <3 months)

Figure 36Academic (general, self, 1-10, high is good, PT >3 months)

Figure 37ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 38ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 39ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 40ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 41ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 42ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

Figure 43ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 44ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 45ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 46ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 47Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 48Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 49Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 50Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 51Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

Figure 52ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 53ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 54ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 55ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 56ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 57ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 58Responders by CGI-I (PT, <3 months)

Figure 59Quality of life (parent rated, total CHIP-CE, unclear range, high is good outcome, CS, PT <3 months)

Figure 60ADHD symptoms (total, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)

Figure 61symptoms (hyperactivity, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)

Figure 62ADHD symptoms (inattention, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months)

Figure 63Academic (parent rated, academic CHIP-CE, unclear range, high is good outcome, CS, PT <3 months)

Figure 64ADHD symptoms (total, parent, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months)

Figure 65ADHD symptoms (total, self, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months)

Figure 66Responders by CGI-I (PT, <3 months)

Figure 67ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 68ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 69ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 70ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 71ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 72symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 73ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 74ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 75ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 76ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 77ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 78symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 79ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 80ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 81ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 82ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 83ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 84symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 85Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 86Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

Figure 87Academic (general, self, SRQ, 1-10, high is good, PT >3 months)

Figure 88ADHD symptoms (total, observer, ADHD-RS, 0-68, high is poor, FV, PT, >3 months)

Figure 89ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 90ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

Figure 91ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 92ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 93ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 94ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 95Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 96Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 97Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 98Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 99Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

Figure 100ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 101ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 102ADHD symptoms (hyperactivity, parent, multiple scales, higher is worse, FV, PT <3 months)

Figure 103ADHD symptoms (hyperactivity, teacher, multiple scales, higher is worse, FV, PT <3 months)

Figure 104ADHD symptoms (inattention, parent, multiple scales, higher is worse, FV, PT <3 months)

Figure 105ADHD symptoms (inattention, teacher, multiple scales, higher is worse, FV, PT <3 months)

Figure 106Responders by CGI-I (PT, <3 months)

Figure 107Behaviour/function (behaviour, 0-100, high is good, teacher, PT, <3 months)

Figure 108ADHD symptoms (total, parent, multiple scales, high is poor, FV, PT, >3 months)

Figure 109ADHD symptoms (total, parent, SWAN, 0-3, high is poor, FV, FU, >3 months)

Figure 110symptoms (total, teacher, DBDRS, 0-54, high is poor, FV, PT, <3 months)

Figure 111ADHD symptoms (hyperactivity, parent, multiple scales, 0-3, high is poor, FV, PT, >3 months)

Figure 112ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 113ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 114ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 115symptoms (inattention, parent, FBB-ADHS, 0-3, high is poor, FV, PT, >3 months)

Figure 116Behaviour/function (function, parent, WFIRS-P, 0-3, high is poor, FV, PT, >3 months)

Figure 117ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 118ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 119ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months)

Figure 120symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months)

Figure 121ADHD symptoms (total, parent, Conners 48, 0-70, high is poor, FV, <3 months PT)

Figure 122ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 123ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 124ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 125ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 126ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 127ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 128ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 129ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 130ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 131ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 132ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 133ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 134ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 135ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months)

Figure 136ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months)

Figure 137ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, <3 months)

Figure 138symptoms (inattention, self-rated, SRQ, 1-10, high is good, PT, >3 months)

Figure 139ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 140Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months)

Figure 141Academic (general, self, SRQ, 1-10, high is good, PT <3 months)

Figure 142Academic (general, self, SRQ, 1-10, high is good, PT >3 months)

Figure 143ADHD symptoms (total, parent, ADHD-RS-IV,0-54, high is poor, CS, FU, >3 months)

Figure 144symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 145ADHD symptoms (hyperactivity, teacher, Conner’s, 0-20, high is poor, FV, PT, <3 months)

Figure 146ADHD symptoms (hyperactivity, teacher, multiple scales, high is poor, FV, PT, >3 months)

Figure 147ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 148ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 149symptoms (hyperactivity, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

Figure 150ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 151ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 152ADHD symptoms (inattention, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months)

Figure 153Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT <3 months)

Figure 154Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT >3 months)

Figure 155Emotional dysregulation (CBRS emotional distress subscale, 0-20, high is poor, teacher, PT <3 months)

Figure 156Emotional dysregulation (CBRS emotional distress subscale, 0-20, high is poor, teacher, PT >3 months)

Figure 157Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 158Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 159Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 160Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 161Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

Figure 162Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT <3 months)

Figure 163Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT >3 months)

Figure 164ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 165ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 166ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 167ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 168ADHD symptoms (hyperactivity, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 169ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 170ADHD symptoms (inattention, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 171ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months)

Figure 172ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

Figure 173ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

Figure 174ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

Figure 175ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

Figure 176Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, PT <3 months)

Figure 177Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, FU >3 months)

Figure 178Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, PT <3 months)

Figure 179Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, FU >3 months)

Figure 180ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 181ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 182ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 183ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 184ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 185ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 186ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 187ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 188ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 189ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months)

Figure 190ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 191ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months)

Figure 192Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, <3 months PT

Figure 193Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, >3 months PT

Figure 194ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT <3 months)

Figure 195Behaviour/function (CBRS, parent, unclear scale, high is poor, FV, PT <3 months)

Figure 196ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 197ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 198ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 199ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 200ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 201ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months)

Figure 202Responders by CGI-I (PT, <3 months)

Figure 203ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months)

Figure 204ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months)

Figure 205ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 206ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 207ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 208ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months)

Figure 209Academic outcomes (maths accuracy %, observer, high is better, PT <3 months)

Figure 210Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 211Academic outcomes (reading accuracy %, observer, high is better, PT <3 months)

Figure 212Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months)

Figure 213Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months)

Figure 214ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 215ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 216ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 217ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 218ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 219ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 220ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 221ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 222ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 223ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months)

Figure 224ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 225ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months)

Figure 226ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 227ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 228ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 229ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 230Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

Figure 231ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 232ADHD symptoms (total, self, multiple tools, decreased by >30%, >3 months PT)

Figure 233ADHD symptoms (total, observer, TAADDS, decreased by >30%, >3 months PT)

Figure 234ADHD symptoms (total, observer, multiple tools, high is worse, FV, >3 months PT)

Figure 235ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 236symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 237Emotional dysregulation (multiple tools, 0-15, high is poor, FV, >3 months PT)

Figure 238Responders by CGI-I (>3 months PT)

Figure 239Responders by CGI-I (>3 months FU)

Figure 240ADHD symptoms (total, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

Figure 241ADHD symptoms (hyperactivity, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

Figure 242ADHD symptoms (inattention, observer, CAARS, 0-36, high is poor, FV, >3 months PT)

Figure 243Child’s ADHD symptoms (total, parent, SDQ, 0-10, high is poor, FV, >3 months PT)

Figure 244Emotional dysregulation (parent, SDQ, 0-10, high is poor, FV, >3 months PT)

Figure 245ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 246symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 247ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 248ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 249Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

Figure 250QoL (Flanagan, 16-112, high is good, FV, <3 months PT)

Figure 251QoL (Flanagan, 16-112, high is good, FV, <3 months FU)

Figure 252ADHD symptoms (total, observer, ADHD-RS, 0-54, higher is worse, FV, PT >3 months)

Figure 253ADHD symptoms (total, self, ADHD-RS, 0-54, higher is worse, FV, PT >3 months)

Figure 254ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months PT)

Figure 255ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months FU)

Figure 256ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months PT)

Figure 257ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months FU)

Figure 258symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months PT)

Figure 259ADHD symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months FU)

Figure 260Responders by CGI

Figure 261Emotional dysregulation (HAM-D, observer, 0-53, high is worse, FV, >3 months PT)

Figure 262Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months PT)

Figure 263Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months FU)

Figure 264Behaviour/function (Self-rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months PT)

Figure 265Behaviour/function (Self-rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months FU)

Figure 266QoL (QLESQ, unclear scale, high is better, FV, >3 months PT)

Figure 267ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months PT)

Figure 268ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months FU)

Figure 269ADHD symptoms (hyperactivity, self, CAARS, high is worse, FV, 0-27, >3 months PT)

Figure 270ADHD symptoms (inattention, self, CAARS, high is worse, FV, 0-27, >3 months PT)

Figure 271CGI-I responders (>3 months PT)

Figure 272Emotional dysregulation (Self, BDI, 0-63, high is worse, FV, >3 months PT)

Figure 273ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 274ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 275ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 276ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT)

Figure 277Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT)

Table 49Clinical evidence profile: Atomoxetine versus Parent/Family training for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Atomoxetine	PT/FT	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.21 lower (0.5 lower to 0.08 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.03 higher (0.35 lower to 0.41 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.32 lower (0.68 lower to 0.04 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.04 higher (0.43 lower to 0.51 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.09 lower (0.41 lower to 0.23 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.02 higher (0.37 lower to 0.41 higher)	⨁◯◯◯ VERY LOW	CRITICAL
Responders by CGI-I (PT, <3 months) (follow-up 10 weeks)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	15/32 (46.9%)	29%	RR 1.61 (0.83 to 3.13)	177 more per 1000 (from 49 fewer to 618 more)	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 50Clinical evidence profile: Stimulants versus exercise for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants	Exercise	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (hyperactivity, parent, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	37	-	MD 0.45 lower (0.84 to 0.06 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	33	37	-	MD 0.87 lower (1.3 to 0.44 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	37	-	MD 0.50 lower (0.86 to 0.14 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, teacher, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	33	37	-	MD 0.76 lower (1.12 to 0.4 lower)	⨁⨁⨁◯ MODERATE	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 51Clinical evidence profile: Stimulants versus Neurofeedback for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants	NF	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 4.60 higher (0.46 to 8.74 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious³	none	28	24	-	MD 0.30 lower (5.21 lower to 4.61 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 2.70 higher (2.93 lower to 8.33 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 0.80 higher (4.45 lower to 6.05 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 3.00 higher (0.49 to 5.51 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 1.40 higher (1.43 lower to 4.23 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious²	none	36	39	-	MD 0.40 lower (0.79 to 0.01 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 0.40 higher (3.33 lower to 4.13 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 2.50 higher (0.59 lower to 5.59 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious²	none	33	39	-	MD 0.93 lower (1.39 to 0.47 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious³	none	27	25	-	MD 0.10 lower (1.63 lower to 1.43 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 0.60 higher (0.90 lower to 2.10 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 0.10 higher (1.18 lower to 1.38 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 1.60 higher (0.91 lower to 4.11 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 1.80 lower (4.42 lower to 0.82 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious²	none	36	39	-	MD 0.50 lower (0.84 to 0.16 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 2.30 higher (0.55 lower to 5.15 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 1.70 lower (4.53 lower to 1.13 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, SWAN, 0-3, high is poor, FV, PT <3 months) (follow-up 10-12 weeks; Better indicated by lower values)
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious²	none	33	39	-	MD 0.73 lower (1.09 to 0.37 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 0.20 higher (1.02 lower to 1.42 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 0.40 higher (0.68 lower to 1.48 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <³ months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	27	25	-	MD 0.40 lower (1.75 lower to 0.95 higher)	⨁◯◯◯ VERY LOW	CRITICAL
Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	27	24	-	MD 1.40 lower (3.22 lower to 0.42 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic (general, self, SRQ, 1-10, high is good, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	31	30	-	MD 0.60 higher (0.90 lower to 2.10 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic (general, self, SRQ, 1-10, high is good, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	24	-	MD 0.10 higher (1.18 lower to 1.38 higher)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

4: Downgraded by 2 increments if the confidence interval crossed both MIDs.

Table 52Clinical evidence profile: Stimulants + NSST versus stimulants for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + NSST versus stimulants	Control	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	4	-	MD 0.10 lower (0.38 lower to 0.18 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	34	-	MD 0.20 lower (0.44 lower to 0.04 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	34	-	MD 0.30 lower (0.68 lower to 0.08 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	34	-	MD 0.40 lower (0.7 to 0.1 lower)	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 53Clinical evidence profile: Mixed medication versus PT/FT for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication	PT/FT	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	115	127	-	MD 0.06 lower (0.21 lower to 0.09 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	120	119	-	MD 0.28 lower (0.47 to 0.09 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	121	129	-	MD 0.33 lower (0.5 to 0.16 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	110	107	-	MD 0.13 lower (0.19 to 0.07 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	121	129	-	MD 0.28 lower (0.45 to 0.11 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	120	120	-	MD 0.36 lower (0.56 to 0.16 lower)	⨁⨁◯◯ LOW	CRITICAL
Academic outcomes (maths accuracy, observer, %, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	39	-	MD 4.14 lower (7.04 to 1.24 lower)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	124	134	-	MD 0.60 lower (3.86 lower to 2.66 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (reading accuracy %, observer, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	36	-	MD 5.45 lower (9.36 to 1.54 lower)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	124	134	-	MD 1.70 higher (1.84 lower to 5.24 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	115	127	-	MD 0.50 lower (3.98 lower to 2.98 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 54Clinical evidence profile: Atomoxetine + PT/FT versus PT/FT for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Atomoxetine + PT/FT	PT/FT	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.22 lower (0.54 lower to 0.1 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.32 lower (0.72 lower to 0.08 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.29 lower (0.65 lower to 0.07 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.30 lower (0.77 lower to 0.17 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.15 lower (0.5 lower to 0.2 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.34 lower (0.75 lower to 0.07 higher)	⨁⨁◯◯ LOW	CRITICAL
Responders by CGI-I (PT, <3 months) (follow-up 10 weeks)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	15/31 (48.4%)	29%	RR 1.67 (0.86 to 3.22)	194 more per 1000 (from 41 fewer to 644 more)	⨁⨁◯◯ LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 55Clinical evidence profile: Atomoxetine + PE versus PE for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Atomoxetine + PE	PE	Relative (95% CI)	Absolute	Quality	Importance
Quality of life (parent rated, total CHIP-CE, unclear range, high is good outcome, CS, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	49	50	-	MD 1.40 higher (1.93 lower to 4.73 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	49	50	-	MD 12.70 lower (16.86 to 8.54 lower)	⨁⨁⨁⨁ HIGH	CRITICAL
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	49	50	-	MD 6.20 lower (8.42 to 3.98 lower)	⨁⨁⨁⨁ HIGH	CRITICAL
ADHD symptoms (inattention, parent, ADHD-RS, 0-25, high is poor, CS, PT, <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	49	50	-	MD 6.50 lower (8.5 to 4.5 lower)	⨁⨁⨁⨁ HIGH	CRITICAL
Academic (parent rated, academic CHIP-CE, unclear range, high is good outcome, CS, PT <3 months) (follow-up 10 weeks; Better indicated by higher values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	49	50	-	MD 4.30 higher (0.83 to 7.77 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 56Clinical evidence profile: Atomoxetine + CBT versus CBT for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Atomoxetine + CBT	CBT	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	33	-	MD 5.00 higher (1.87 lower to 11.87 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, self, DSM-IV checklist, 0-54, high is poor, CS, PT <3 months) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	33	-	MD 0.83 lower (7.52 lower to 5.86 higher)	⨁⨁◯◯ LOW	CRITICAL
Responders by CGI-I (PT, <3 months) (follow-up 12 weeks)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious³	none	17/32 (53.1%)	60.6%	RR 0.88 (0.57 to 1.34)	73 fewer per 1000 (from 261 fewer to 206 more)	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the confidence interval crossed both MIDs.

Table 57Clinical evidence profile: Stimulants + NF versus NF for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + NF	NF	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 1.10 higher (3.03 lower to 5.23 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 1.10 lower (6.01 lower to 3.81 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 0.10 higher (5.87 lower to 6.07 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 3.20 lower (8.73 lower to 2.33 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 0.30 higher (2.21 lower to 2.81 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 0.90 higher (2.00 lower to 3.80 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 2.10 lower (6.03 lower to 1.83 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	29	24	-	MD 0.00 higher (3.24 lower to 3.24 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 1.20 higher (0.36 lower to 2.76 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, >3 months) (follow-up 6 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 0.10 higher (1.18 lower to 1.38 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	25	-	MD 0.40 lower (2 lower to 1.2 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 0.80 higher (1.71 lower to 3.31 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 2.10 lower (4.79 lower to 0.59 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 2.20 higher (0.78 lower to 5.18 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 3.20 lower (6.17 to 0.23 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 0.20 lower (1.42 lower to 1.02 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	24	-	MD 1.30 higher (0.22 to 2.38 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	25	-	MD 0.60 lower (1.88 lower to 0.68 higher)	⨁◯◯◯ VERY LOW	CRITICAL
Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	22	24	-	MD 2.50 lower (4.31 to 0.69 lower)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic (general, self, SRQ, 1-10, high is good, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 1.20 higher (0.36 lower to 2.76 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic (general, self, SRQ,1-10, high is good, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision²	none	29	24	-	MD 0.10 higher (1.18 lower to 1.38 higher)	⨁⨁◯◯ LOW	IMPORTANT

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 58Clinical evidence profile: Stimulants + CBT versus CBT for ADHD in children and young people

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Stimulants + CBT

CBT

Relative (95% CI)

Absolute

ADHD symptoms (total, observer, ADHD-RS, 0-68, high is poor, FV, PT, >3 months) (follow-up 16 weeks; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

no serious imprecision

none

151

152

MD 0.60 higher (1.04 lower to 2.24 higher)

⨁⨁⨁⨁

HIGH

CRITICAL

Table 59Clinical evidence profile: Mixed medication + PT/FT versus PT/FT for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + PT/FT	PT/FT	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	127	127	-	MD 0.07 lower (0.21 lower to 0.07 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	134	119	-	MD 0.35 lower (0.53 to 0.17 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	133	129	-	MD 0.61 higher (0.45 to 0.77 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	114	107	-	MD 0.08 lower (0.14 to 0.02 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	133	129	-	MD 0.38 lower (0.54 to 0.22 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	134	120	-	MD 0.35 lower (0.54 to 0.16 lower)	⨁⨁◯◯ LOW	CRITICAL
Academic outcomes (maths accuracy %, observer, high is better, PT <3 months) (follow-up 8 days; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	39	-	MD 0.99 lower (3.42 lower to 1.44 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	no serious imprecision	none	136	134	-	MD 0.20 higher (3.4 lower to 3.8 higher)	⨁⨁◯◯ LOW	IMPORTANT
Academic outcomes (reading accuracy %, observer, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	36	-	MD 1.17 lower (4.34 lower to 2 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	136	134	-	MD 3.20 higher (0.39 lower to 6.79 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	127	127	-	MD 0.60 lower (4.02 lower to 2.82 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 60Clinical evidence profile: Atomoxetine + PT/FT versus atomoxetine for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Atomoxetine + PT/FT	Atomoxetine	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.01 lower (0.32 lower to 0.3 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.35 lower (0.73 lower to 0.03 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, multiple scales, higher is worse, FV, PT <3 months) (follow-up 8-10 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	61	59	-	SMD 0.21 lower (0.57 lower to 0.15 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, multiple scales, higher is worse, FV, PT <3 months) (follow-up 8-10 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	61	59	-	SMD 0.16 lower (0.52 lower to 0.2 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, multiple scales, higher is worse, FV, PT <3 months) (follow-up 8-10 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	61	59	-	SMD 0.37 lower (0.73 to 0.01 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, multiple scales, higher is worse, FV, PT <3 months) (follow-up 8-10 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	61	59	-	SMD 0.38 lower (0.74 to 0.02 lower)	⨁◯◯◯ VERY LOW	CRITICAL
Responders by CGI-I (PT, <3 months) (follow-up 8-10 weeks)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious³	none	31/60 (51.7%)	49.4%	RR 1.05 (0.73 to 1.5)	25 more per 1000 (from 133 fewer to 247 more)	⨁◯◯◯ VERY LOW	CRITICAL
Behaviour/function (behaviour, 0-100, high is good, teacher, PT, <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	27	-	MD 5.06 higher (4.59 lower to 14.71 higher)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the confidence interval crossed both MIDs.

Table 61Clinical evidence profile: Stimulants + PT/FT versus stimulants for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + PT/FT	Stimulants	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, multiple scales, high is poor, FV, PT, >3 months) (follow-up 2-12 months; Better indicated by lower values)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	120	104	-	SMD 0.42 lower (0.69 to 0.15 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, parent, SWAN, 0-3, high is poor, FV, FU, >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	44	31	-	MD 0.13 lower (0.39 lower to 0.13 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, teacher, DBDRS, 0-54, high is poor, FV, PT, <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	21	-	MD 2.15 higher (3.48 lower to 7.78 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, FBB-ADHS, 0-3, high is poor, FV, PT, >3 months) (follow-up 12 months; Better indicated by lower values)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	51	86	-	SMD 0.05 lower (0.35 lower to 0.25 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	34	34	-	MD 0.10 lower (0.36 lower to 0.16 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	34	34	-	MD 0.30 lower (0.7 lower to 0.1 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	34	34	-	MD 0.10 lower (0.46 lower to 0.26 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, FBB-ADHS, 0-3, high is poor, FV, PT, >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	52	-	MD 0.29 lower (0.53 to 0.05 lower)	⨁⨁◯◯ LOW	CRITICAL
Behaviour/function (function, parent, WFIRS-P, 0-3, high is poor, FV, PT, >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	52	-	MD 0.10 lower (0.3 lower to 0.1 higher)	⨁⨁◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 62Clinical evidence profile: Stimulants + PT/FT versus stimulants + NSST for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + PT/FT versus stimulants + NSST	Control	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, PT >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	34	35	-	MD 0.20 higher (0.08 lower to 0.48 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, CTRS, 0-3, higher is worse, FV, FU >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	34	35	-	MD 0.10 higher (0.11 lower to 0.31 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, PT >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	34	35	-	MD 0 higher (0.36 lower to 0.36 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, CTRS, 0-3, higher is worse, FV, FU >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	34	35	-	MD 0.30 higher (0.03 to 0.57 higher)	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 63Clinical evidence profile: Stimulants + attention/memory/cognitive training versus stimulants for ADHD in children and young people

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Stimulants + attention/memory/cognitive training

Stimulants

Relative (95% CI)

Absolute

ADHD symptoms (total, parent, Conners 48, 0-70, high is poor, FV, <3 months PT) (follow-up <3 months; Better indicated by lower values)

randomised trials

very serious¹

no serious inconsistency

no serious indirectness

no serious imprecision

none

MD 8.67 lower (11.5 to 5.84 lower)

⨁⨁◯◯

LOW

CRITICAL

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 64Clinical evidence profile: Stimulants + NF versus stimulants for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + NF	Stimulants	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 3.50 lower (7.57 lower to 0.57 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	0	-	-	MD 0.80 lower (5.67 lower to 4.07 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 2.60 lower (8.51 lower to 3.31 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	28	-	MD 4.00 lower (9.55 lower to 1.55 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 2.70 lower (5.14 to 0.26 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	28	-	MD 0.50 lower (3.27 lower to 2.27 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 2.50 lower (6.37 lower to 1.37 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	28	-	MD 1.50 lower (5.64 lower to 2.64 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 0.60 higher (0.83 lower to 2.03 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self-rated, SRQ, 1-10, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious³	none	29	28	-	MD 0.00 higher (1.22 lower to 1.22 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	27	-	MD 0.30 lower (1.87 lower to 1.27 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 0.80 lower (3.05 lower to 1.45 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	28	-	MD 0.30 lower (2.94 lower to 0 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 0.10 lower (3.16 lower to 2.96 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, Barkley’s, 0-54, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	28	-	MD 1.50 lower (4.48 lower to 1.48 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 0.40 lower (1.62 lower to 0.82 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self-rated, SRQ, 1-10, high is poor, PT, >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	28	-	MD 0.90 higher (0.18 lower to 1.98 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	27	-	MD 0.20 lower (1.58 lower to 1.18 higher)	⨁◯◯◯ VERY LOW	CRITICAL
Academic (general, self, SRQ, 1-10, high is good, CS, PT <3 months) (follow-up <3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	22	27	-	MD 1.10 lower (2.84 lower to 0.64 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic (general, self, SRQ, 1-10, high is good, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	31	-	MD 0.60 higher (0.83 lower to 2.03 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic (general, self, SRQ, 1-10, high is good, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious³	none	29	28	-	MD 0.00 higher (1.22 lower to 1.22 higher)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 65Clinical evidence profile: Mixed medication + PT/FT versus mixed medication for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + PT/FT	Mixed medication	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	144	126	-	SMD 0.27 lower (0.51 to 0.03 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	127	115	-	MD 0.01 lower (0.15 lower to 0.13 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, teacher, Conner’s, 0-20, high is poor, FV, PT, <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	27	27	-	MD 2.22 higher (4.38 lower to 8.82 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, multiple scales, high is poor, FV, PT, >3 months) (follow-up 3-14 months; Better indicated by lower values)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	162	147	-	SMD 0.05 lower (0.28 lower to 0.17 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	133	121	-	MD 0.94 higher (0.78 to 1.1 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	114	110	-	MD 0.05 higher (0 to 0.1 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	no serious imprecision	none	144	126	-	SMD 0.22 lower (0.46 lower to 0.02 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	133	121	-	MD 0.10 lower (0.27 lower to 0.07 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	134	120	-	MD 0.01 higher (0.18 lower to 0.2 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, parent, ADHD-RS-IV, 0-54, high is poor, CS, FU, >3 months) (follow-up 12 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	144	126	-	SMD 0.27 lower (0.51 to 0.03 lower)	⨁◯◯◯ VERY LOW	CRITICAL
Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	27	26	-	MD 1.58 lower (8.11 lower to 4.95 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Behaviour/function (CBRS aggressive behaviour subscale, 0-15, high is poor, teacher, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	28	27	-	MD 2.28 lower (8.8 lower to 4.24 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Emotional dysregulation (CBRS emotional distress subscale, 0-15, high is poor, teacher, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	27	26	-	MD 4.22 higher (2.14 lower to 10.58 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Emotional dysregulation (CBRS emotional distress subscale, 0-15, high is poor, teacher, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	28	27	-	MD 2.35 higher (4.16 lower to 8.86 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (maths accuracy %, observer, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	36	-	MD 3.15 higher (0.15 to 6.15 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	136	124	-	MD 0.80 higher (2.78 lower to 4.38 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (reading accuracy %, observer, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	36	-	MD 4.28 higher (0.3 to 8.26 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	136	124	-	MD 1.50 higher (2.06 lower to 5.06 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (reading accuracy, observer, 0-132, high is better, FU >3 months) (follow-up median 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	127	115	-	MD 0.10 lower (3.53 lower to 3.33 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	24	26	-	MD 2.25 higher (4.95 lower to 9.45 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (general, CBRS academic subscale, 0-30, high is poor, teacher, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	26	27	-	MD 0.48 lower (7.09 lower to 6.13 higher)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 66Clinical evidence profile: Mixed medication + CBT versus mixed medication for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + CBT	Mixed medication	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 4 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	46	46	-	SMD 1.08 lower (1.52 to 0.64 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months) (follow-up 12 sessions; Better indicated by lower values)
1	randomised trials	very serious²	no serious inconsistency	no serious indirectness	no serious imprecision	none	59	60	-	MD 7.62 lower (7.98 to 7.26 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months) (follow-up 12 sessions; Better indicated by lower values)
1	randomised trials	very serious²	no serious inconsistency	no serious indirectness	no serious imprecision	none	59	60	-	MD 9.39 lower (9.79 to 8.99 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 4 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	46	46	-	SMD 2.21 lower (2.74 to 1.69 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months) (follow-up 12 sessions; Better indicated by lower values)
1	randomised trials	very serious²	no serious inconsistency	no serious indirectness	no serious imprecision	none	59	60	-	MD 3.43 lower (3.74 to 3.12 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months) (follow-up 12 sessions; Better indicated by lower values)
1	randomised trials	very serious²	no serious inconsistency	no serious indirectness	no serious imprecision	none	59	60	-	MD 3.84 lower (4.12 to 3.56 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, self, ADHD-RS, 0-54, high is poor, FV, PT >3 months) (follow-up 12 sessions; Better indicated by lower values)
1	randomised trials	very serious²	no serious inconsistency	no serious indirectness	no serious imprecision	none	59	60	-	MD 4.33 lower (4.51 to 4.15 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, FV, PT >3 months) (follow-up 12 sessions; Better indicated by lower values)
1	randomised trials	very serious²	no serious inconsistency	no serious indirectness	no serious imprecision	none	59	60	-	MD 5.68 lower (5.89 to 5.47 lower)	⨁⨁◯◯ LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 67Clinical evidence profile: Mixed medication + PE versus mixed medication + NSST for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + PE	Mixed medication + NSST	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, PT <3 months) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	42	36	-	MD 1.71 lower (3.67 lower to 0.25 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, CPRS, 0-27, high is poor, FV, FU >3 months) (follow-up 64 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	36	-	MD 1.07 lower (3.02 lower to 0.88 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, PT <3 months) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	42	36	-	MD 3.05 lower (4.63 to 1.47 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, CPRS, 0-27, high is poor, FV, FU >3 months) (follow-up 64 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	36	-	MD 2.15 lower (3.93 to 0.37 lower)	⨁⨁◯◯ LOW	CRITICAL
Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, PT <3 months) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	42	36	-	MD 1.23 lower (2.94 lower to 0.48 higher)	⨁⨁◯◯ LOW	IMPORTANT
Behaviour/function (opposition, parent, CPRS, 0-27, high is poor, FV, FU >3 months) (follow-up 64 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	36	-	MD 0.43 lower (2.21 lower to 1.35 higher)	⨁⨁◯◯ LOW	IMPORTANT
Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, PT <3 months) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	40	36	-	MD 0.11 lower (1.21 lower to 0.99 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Emotional dysregulation (SDQ, parent, 0-25, high is poor, FV, FU >3 months) (follow-up 64 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	36	-	MD 0.29 lower (1.32 lower to 0.74 higher)	⨁⨁◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 68Clinical evidence profile: Mixed medication + sleep intervention versus mixed medication for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + sleep intervention	Mixed medication	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	122	122	-	SMD 0.21 lower (0.46 lower to 0.04 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.39 lower (0.64 to 0.13 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	122	122	-	SMD 0.18 lower (0.43 lower to 0.07 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.41 lower (0.66 to 0.15 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.28 lower (0.53 to 0.03 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.27 lower (0.52 to 0.02 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 6 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	122	122	-	SMD 0.18 lower (0.44 lower to 0.07 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.29 lower (0.54 to 0.04 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	122	122	-	SMD 0.11 lower (0.36 lower to 0.14 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT <3 months) (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.43 lower (0.68 to 0.18 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	122	122	-	SMD 0.11 lower (0.36 lower to 0.14 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, parent, ADHD-RS, 0-54, high is poor, CS, PT >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.46 lower (0.72 to 0.21 lower)	⨁◯◯◯ VERY LOW	CRITICAL
Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, <3 months PT (follow-up 3 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	122	122	-	SMD 0.25 lower (0.5 lower to 0 higher)	⨁⨁◯◯ LOW	IMPORTANT
Behaviour/function (teacher, SDQ, 0-54, high is poor, CS, >3 months PT (follow-up 6 months; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	122	122	-	SMD 0.32 lower (0.57 to 0.06 lower)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 69Clinical evidence profile: Mixed medication + NF versus mixed medication for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + NF	Mixed medication	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, ADHD-RS, 0-54, high is poor, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	18	-	MD 4.44 lower (7.07 to 1.81 lower)	⨁⨁◯◯ LOW	CRITICAL
Behaviour/function (CBRS, parent, unclear scale, high is poor, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	18	-	MD 3.72 lower (6.96 to 0.48 lower)	⨁⨁◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 70Clinical evidence profile: Atomoxetine + PT/FT versus placebo/usual care for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Atomoxetine + PT/FT	Placebo/usual care	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.51 lower (0.89 to 0.13 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.30 lower (0.71 lower to 0.11 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.54 lower (0.96 to 0.12 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.27 lower (0.72 lower to 0.18 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.49 lower (0.87 to 0.11 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, higher is worse, FV, PT <3 months) (follow-up 10 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	32	-	MD 0.33 lower (0.78 lower to 0.12 higher)	⨁◯◯◯ VERY LOW	CRITICAL
Responders by CGI-I (PT, <3 months) (follow-up 10 weeks)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	15/31 (48.4%)	19.4%	RR 2.5 (1.12 to 5.59)	291 more per 1000 (from 23 more to 890 more)	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 71Clinical evidence profile: Mixed medication + PT/FT versus placebo/usual care for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mixed medication + PT/FT	Placebo/usual care	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, teacher and parent, SNAP, 0-3, high is poor, FV, FU >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	127	116	-	MD 0.06 lower (0.2 lower to 0.08 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, teacher, SNAP, 0-3, high is poor, FV, PT, >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	134	128	-	MD 0.50 lower (0.69 to 0.31 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	133	130	-	MD 0.50 higher (0.34 to 0.66 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, observer, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	114	109	-	MD 0.03 higher (0.02 lower to 0.08 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, parent, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	133	130	-	MD 0.47 lower (0.63 to 0.31 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, teacher, SNAP, 0-3, high is poor, FV, PT >3 months) (follow-up 14 months; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	134	128	-	MD 0.36 lower (0.55 to 0.17 lower)	⨁⨁◯◯ LOW	CRITICAL
Academic outcomes (maths accuracy %, observer, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	serious³	no serious inconsistency	no serious indirectness	serious²	none	39	36	-	MD 7.05 higher (3.69 to 10.41 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (maths accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	136	131	-	MD 0.10 higher (3.69 lower to 3.89 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Academic outcomes (reading accuracy %, observer, high is better, PT <3 months) (follow-up 8 weeks; Better indicated by higher values)
1	randomised trials	very serious³	no serious inconsistency	no serious indirectness	serious²	none	39	36	-	MD 7.66 higher (3.35 to 11.97 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, PT >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	136	131	-	MD 4.00 higher (0.47 to 7.53 higher)	⨁⨁◯◯ LOW	IMPORTANT
Academic outcomes (reading accuracy, observer, WIAT, 0-132, high is better, FU >3 months) (follow-up 14 months; Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	127	116	-	MD 1.70 higher (1.87 lower to 5.27 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed one MID.

3: Downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

Table 72Clinical evidence profile: Stimulants + NF versus stimulants + attention/memory/cognitive training for ADHD in children and young people

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + NF	Stimulants + attention/memory/cognitive training	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months) (follow-up 8-20 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	32	32	-	MD 2.60 lower (6.97 lower to 1.77 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months) (follow-up 8-20 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	32	32	-	MD 3.90 lower (8.79 lower to 0.99 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	31	29	-	MD 7.00 lower (10.85 to 3.15 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	31	29	-	MD 8.70 lower (13.12 to 4.28 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months) (follow-up 8-20 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	32	32	-	MD 0.70 lower (3.42 lower to 2.02 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months) (follow-up 8-20 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	32	32	-	MD 1.60 lower (4.57 lower to 1.37 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	31	29	-	MD 3.20 lower (5.83 to 0.57 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	31	29	-	MD 3.70 lower (6.89 to 0.51 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, PT <3 months) (follow-up 8-20 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	32	32	-	MD 1.30 lower (3.83 lower to 1.23 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, PT <3 months) (follow-up 8-20 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	32	32	-	MD 2.40 lower (5.1 lower to 0.3 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, parent, DSM-IV, high is poor, unclear scale, FV, FU >3 months) (follow-up 6 weeks; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	31	29	-	MD 4.10 lower (6.43 to 1.77 lower)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, teacher, DSM-IV, high is poor, unclear scale, FV, FU >3 months) (follow-up 6 months; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	31	29	-	MD 5.50 lower (7.4 to 3.6 lower)	⨁⨁⨁⨁ HIGH	CRITICAL

1: Downgraded by 1 increment if the confidence interval crossed one MID.

Table 73Clinical evidence profile: Stimulants +NSST versus CBT for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + NSST	Control	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 1 years; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	106	107	-	MD 1.80 lower (3.63 lower to 0.03 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 1 years; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	107	103	-	MD 1.80 lower (3.49 to 0.11 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 1 years; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	107	103	-	MD 1.60 lower (3.41 lower to 0.21 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 1 years; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	106	107	-	MD 0.80 higher (0.95 lower to 2.55 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT) (follow-up 1 years; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	107	103	-	MD 0.20 higher (1.77 lower to 2.17 higher)	⨁⨁⨁◯ MODERATE	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs

Table 74Clinical evidence profile: Stimulants + CBT/DBT versus CBT/DBT for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + CBT/DBT	CBT/DBT alone	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 1 years; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	106	-	MD 1.60 lower (2.5 to 0.7 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, self, multiple tools, decreased by >30%, >3 months PT) - General population (follow-up 14 weeks)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none	25/53 (47.2%)	54.7%	RR 0.86 (0.59 to 1.26)	77 fewer per 1000 (from 224 fewer to 142 more)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, self, multiple tools, decreased by >30%, >3 months PT) - Secure estate (follow-up 24 weeks)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	17/27 (63%)	26.9%	RR 2.34 (1.17 to 4.69)	360 more per 1000 (from 46 more to 993 more)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, observer, TAADDS, decreased by >30%, >3 months PT) (follow-up 14 weeks)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious²	none	21/53 (39.6%)	28.3%	RR 1.4 (0.81 to 2.41)	113 more per 1000 (from 54 fewer to 399 more)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, observer, multiple tools, high is worse, FV, >3 months PT) (follow-up 20-52 weeks; Better indicated by lower values)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	126	131	-	SMD 0.43 lower (0.67 to 0.18 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	106	-	MD 1.90 lower (2.84 to 0.96 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	106	-	MD 1.00 lower (1.92 to 0.08 lower)	⨁⨁◯◯ LOW	CRITICAL
Emotional dysregulation (multiple tools, high is poor, FV, >3 months PT) (follow-up 20-52 weeks; Better indicated by lower values)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	126	131	-	SMD 0.06 lower (0.3 lower to 0.19 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Responders by CGI-I (>3 months PT) (follow-up 14 weeks)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none	18/53 (34%)	30.2%	RR 1.12 (0.65 to 1.96)	36 more per 1000 (from 106 fewer to 290 more)	⨁⨁◯◯ LOW	CRITICAL
Responders by CGI-I (>3 months FU) (follow-up 20 weeks)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	15/23 (65.2%)	16%	RR 4.08 (1.58 to 10.5)	493 more per 1000 (from 93 more to 1000 more)	⨁⨁⨁ HIGH	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs

Table 75Clinical evidence profile: Stimulants + CBT/DBT + PT/FT versus NSST + PT/FT for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + CBT/DBT + PT/FT	NSST + PT/FT	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, observer, CAARS, 0-36, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	77	66	-	MD 2.70 lower (4.58 to 0.82 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, observer, CAARS, 0-36, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	77	66	-	MD 3.00 lower (4.88 to 1.12 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, observer, CAARS, 0-36, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	77	66	-	MD 2.70 lower (4.79 to 0.61 lower)	⨁⨁◯◯ LOW	CRITICAL
Child’s ADHD symptoms (total, parent, SDQ, 0-10, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	77	67	-	MD 0.50 lower (1.13 lower to 0.13 higher)	⨁⨁◯◯ LOW	IMPORTANT
Emotional dysregulation (parent, SDQ, 0-10, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	77	67	-	MD 0.20 higher (0.43 lower to 0.83 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs

Table 76Clinical evidence profile: Stimulants + CBT/DBT versus stimulants + NSST for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + CBT/DBT	Stimulants + NSST	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	110	-	MD 0.20 higher (1.55 lower to 1.95 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	110	-	MD 0.30 higher (1.45 lower to 2.05 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	106	-	MD 0.30 lower (1.98 lower to 1.38 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	106	-	MD 0.20 lower (1.88 lower to 1.48 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	110	-	MD 0.70 lower (2.66 lower to 1.26 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

Table 77Clinical evidence profile: Medication + CBT/DBT versus medication for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Medication + CBT/DBT	Medication alone	Relative (95% CI)	Absolute	Quality	Importance
QoL (Flanagan, 16-112, high is good, FV, <3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	34	35	-	MD 3.60 higher (3.68 lower to 10.88 higher)	⨁◯◯◯ VERY LOW	CRITICAL
QoL (Flanagan, 16-112, high is good, FV, <3 months FU) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	32	-	MD 7.62 higher (1.03 to 14.21 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, observer, ADHD-RS, 0-54, higher is worse, FV, PT >3 months) (follow-up 15 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	15	-	MD 5.61 lower (12.11 lower to 0.89 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, self, ADHD-RS, 0-54, higher is worse, FV, PT >3 months) (follow-up 15 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	15	-	MD 9.12 lower (15.69 to 2.55 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months PT) (follow-up 8-12 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	52	52	-	5.01 lower (8.30 to 1.72 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, self, Barkley, 0-54, high is poor, FV, <3 months FU) (follow-up 12 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	49	-	8.23 lower (11.86 lower to 4.61 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months PT) (follow-up 8-12 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	52	52	-	1.36 lower (3.46 lower to 0.74 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self, Barkley, 0-27, high is poor, FV, <3 months FU) (follow-up 12 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	49	-	2.97 lower (4.90 to 1.03 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months PT) (follow-up 8-12 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	52	52	-	3.63 lower (5.55 to 1.71 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self, Barkley, 0-27, high is poor, FV, <3 months FU) (follow-up 12 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	49	-	5.26 lower (7.60 to 2.93 lower)	⨁◯◯◯ VERY LOW	CRITICAL
Responders by CGI (two point change in CGI-S, >3 months PT) (follow-up 15 weeks)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	9/16 (56.3%)	13.3%	RR 4.22 (1.08 to 16.45)	428 more per 1000 (from 11 more to 1000 more)	⨁⨁◯◯ LOW	CRITICAL
Emotional dysregulation (observer, HAM-D, 0-53, high is worse, FV, >3 months PT) (follow-up 15 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	15	-	MD 5.56 lower (9.71 to 1.41 lower)	⨁⨁◯◯ LOW	IMPORTANT
Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	34	34	-	MD 5.62 lower (9.85 to 1.39 lower)	⨁◯◯◯ VERY LOW	IMPORTANT
Emotional dysregulation (Self, BDI, 0-64, high is worse, FV, <3 months FU) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	24	29	-	MD 8.10 lower (11.72 to 4.43 lower)	⨁⨁◯◯ LOW	IMPORTANT
Behaviour/function (Self-rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	33	35	-	MD 1.05 lower (1.99 to 0.11 lower)	⨁◯◯◯ VERY LOW	CRITICAL
Behaviour/function (Self-rated, RATE antisocial scale, unclear range, high is worse, FV, <3 months FU) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	32	-	MD 2.43 lower (3.97 to 0.89 lower)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs

Table 78Clinical evidence profile: Medication + CBT/DBT versus Medication + NSST for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Medication + CBT/DBT	Medication + NSST	Relative (95% CI)	Absolute	Quality	Importance
QoL (QLESQ, unclear scale, high is better, FV, >3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	15	17	-	MD 33.10 higher (35.83 lower to 102.03 higher)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months PT) (follow-up 12-15 weeks; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	56	54	-	SMD 0.33 lower (0.7 lower to 0.05 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (total, self, ADHD-RS, high is worse, FV, 0-54, >3 months FU) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	38	32	-	MD 3.58 lower (6.34 to 0.82 lower)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (hyperactivity, self, CAARS, high is worse, FV, 0-27, >3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	15	17	-	MD 1.72 higher (4.41 lower to 7.85 higher)	⨁◯◯◯ VERY LOW	CRITICAL
ADHD symptoms (inattention, self, CAARS, high is worse, FV, 0-27, >3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	15	17	-	MD 1.35 higher (4.62 lower to 7.32 higher)	⨁◯◯◯ VERY LOW	CRITICAL
CGI-I responders (>3 months PT) (follow-up 15 weeks)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	22/41 (53.7%)	24.3%	RR 2.21 (1.17 to 4.16)	294 more per 1000 (from 41 more to 768 more)	⨁◯◯◯ VERY LOW	CRITICAL
Emotional dysregulation (Self, BDI, 0-63, high is worse, FV, >3 months PT) (follow-up 12 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	15	17	-	MD 1.24 lower (9.37 lower to 6.89 higher)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs

Table 79Clinical evidence profile: Stimulants + CBT/DBT versus NSST for ADHD in adults

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Stimulants + CBT/DBT	NSST alone	Relative (95% CI)	Absolute	Quality	Importance
ADHD symptoms (total, self, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	103	-	MD 2.70 lower (4.45 to 0.95 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (total, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	103	-	MD 2.60 lower (4.49 to 0.71 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (hyperactivity, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	103	-	MD 2.20 lower (4.02 to 0.38 lower)	⨁⨁◯◯ LOW	CRITICAL
ADHD symptoms (inattention, observer, CAARS, 0-30, high is worse, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	103	103	-	MD 2.50 lower (4.32 to 0.68 lower)	⨁⨁◯◯ LOW	CRITICAL
Emotional dysregulation (Self, BDI, 0-63, high is poor, FV, >3 months PT) (follow-up 52 weeks; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	103	-	MD 1.20 lower (3.3 lower to 0.9 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs

* Non-relevant population, intervention, comparison, design or setting; non-English language

(a) note that there were 2 original models from the previous guideline (either included or excluded) which is why the numbers add to more than 15.

(b) Two articles identified were applicable to Q5 and Q10, for the purposes of this diagram it has been included under Q5 only.

(c) One of these is a model from the previous guideline that was exclude. Two articles identified were applicable to both Q5 and Q11 and have only been included here under Q11. One paper here was selectively excluded in Q11 but included in Q5 and so is double counted in this flowchart.

Table 80Studies excluded from the clinical review

Study	Exclusion reason
Abbasi 2011²	Incorrect intervention
Aman 2009⁵	Incorrect stratum
Aman 2014⁴	Incorrect population. Sequencing
Arnold 2015⁶	Incorrect population. Sequencing
Babinski 2014⁷	Incorrect study design
Babinski 2014⁸	Incorrect study design
Fabiano 2007¹⁴	Incorrect duration
Farmer 2012¹⁵	No usable outcomes
Farmer 2015¹⁶	Incorrect population. Sequencing
Foster 2007¹⁸	Incorrect stratum. Unusable outcomes
Gallucci 2006¹⁹	Incorrect study design
Helseth 2015²²	No useable outcomes
Heriot 2008²³	Incorrect study design
Janssen 2016²⁷	No relevant outcomes
Kang 2011³⁰	No usable outcomes
Konstenius 2010³³	Incorrect intervention
Meisel 2013⁴⁰	Incorrect intervention
Mesler 2016⁴²	Incorrect stratum. Incorrect interventions
Pelham 2014⁴⁷	Incorrect duration
Pelham 2016⁴⁸	Inappropriate comparison
R.g. klein 1997³²	Inappropriate diagnosis
Schachar 1997⁵³	Incorrect intervention
Tamm 2012⁶⁰	No usable outcomes
Warden 2012⁶⁴	No usable outcomes

Table 81Studies excluded from the health economic review

Reference	Reason for exclusion
Lord & Paisley 2000³⁹	This study was assessed as not applicable, because the cost year (2000) is prior to a 15 year cut-off that the guideline employs for economic evaluations. It is also not using QALYs (cost per SMD in the SNAP-IV score)
Zupancic 1998⁶⁹	This study was assessed as not applicable because of the perspective (Canadian third party payer). The cost year was also before the guideline date cut-off (1997). The outcome is also not QALYs (Change in Conners’ teacher rating scale)
The MTA Co-operative study Jensen et al., 2005 Foster et al., 2007²⁹^,¹⁸	This study was assessed as not applicable because it is a US study and there may be more applicable evidence. The date of costs is also before the guideline date cut-off (2001). The outcomes are also not in QALYs (cost per ‘normalised’ child, and cost per change on CIS-ES).
King 2006³¹	This study was assessed as not applicable because of methodological limitations as the RCT that clinical effectiveness of combination therapy was based on a study that has been excluded from the guideline clinical review.
CG72 model⁴⁵	The previous guideline model on children comparing combination treatments has been selectively excluded because it is not applicable as it is based on clinical evidence that is excluded from the clinical review.

Criteria for selecting high-priority research recommendations

PICO question	Population: Children under the age of 5 with ADHD and their parents or carers Intervention(s): Pharmacological treatment (e.g. methylphenidate, lisdexamfetamine, atomoxetine or guanfacine), non-pharmacological treatment (e.g. parent-training programmes), combination Comparison: Each other (3 arm study) Outcome(s): Quality of life, ADHD symptoms (total, inattention, hyperactivity) assessed by neutral observer and reported as continuous and dichotomous responder outcomes, medication use, behavioural measures, discontinuations, serious adverse events
Importance to patients or the population	Either support or reject the concept of medication use in this age group
Relevance to NICE guidance	Allow for evidence based recommendations on the use of medication or a combination of medication and parent-training programmes in this age group
Relevance to the NHS	Provide framework for guidance around prescribing in this age group
National priorities	NICE ADHD guideline
Current evidence base	There are a small number of studies comparing medication with placebo in this age group, a larger evidence based comparing parent-training programmes with usual care in this age group and no studies comparing the two head to head or in combination There is a lack of evidence measuring the long term effects of treatments for ADHD. As a chronic lifelong condition it is imperative trials have longer follow up measuring the benefits and risks of treatments.
Equality	Research could allow for recommendations tailored to age and not based on consensus and extrapolation from older children
Study design	RCT
Feasibility	Ethics of randomising children in this age group to medication or not are challenging but without RCTs in this population, difficult to recommend an appropriate strategy
Other comments	N/A
Importance	High: the research is essential to inform future updates of key recommendations in the guideline.

Criteria for selecting high-priority research recommendations

PICO question	Population: Children, young people and adults over the age of 5 with ADHD and their parents or carers (if applicable), ideally treatment naïve but if not, to aid recruitment, then results should be stratified by previous treatment and response Intervention(s): Pharmacological treatment (e.g. methylphenidate, lisdexamfetamine, atomoxetine or guanfacine), non-pharmacological treatment (e.g. parent-training programmes in children, CBT in young people and adults), combination Comparison: Each other (3 arm study) Outcome(s): Quality of life, ADHD symptoms (total, inattention, hyperactivity) assessed by neutral observer and reported as continuous and dichotomous responder outcomes, medication use, behavioural measures, discontinuations, serious adverse events
Importance to patients or the population	Would provide better information on relative efficacy of these treatments to allow people to make more informed choices between options
Relevance to NICE guidance	Allow for stronger evidence based recommendations on the use of medication or a combination of medication and non-pharmacological treatments
Relevance to the NHS	Provide framework for guidance around prescribing in this age group
National priorities	NICE ADHD guideline
Current evidence base	There are a large number of small studies comparing these interventions however there is a wide range of baseline population characteristics and precise interventions involved (particularly in terms of non-pharmacological interventions) that makes it difficult to draw conclusions from their meta-analysis There is a lack of evidence measuring the long term effects of treatments for ADHD. As a chronic lifelong condition it is imperative trials have longer follow up measuring the benefits and risks of treatments.
Equality	Research could allow for recommendations tailored to age and not based on consensus and extrapolation from older children
Study design	RCT
Feasibility	Key issue is that study needs to be large enough to be adequately powered and not to be another small comparison that does not fit in readily with previous evidence
Other comments	N/A
Importance	High: the research is essential to inform future updates of key recommendations in the guideline.