Evidence reviews for pharmacological interventions for the prevention and treatment of PTSD in adults

Included studies

Eight studies of SSRIs for the prevention of PTSD in adults were identified for full-text review. Of these 8 studies, 1 RCT (N=31) was included in a single comparison for SSRIs (Suliman 2015). This RCT compared escitalopram with placebo for the early prevention (intervention initiated within 1 month of traumatic event) of PTSD in adults.

Excluded studies

Seven studies were reviewed at full text and excluded from this review. Reasons for exclusion included non-randomised group assignment, small sample size (N<10 per arm), or the paper was a systematic review with no new useable data and any meta-analysis results not appropriate to extract.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 2 provides a brief summary of the included study and evidence from this study is summarised in the clinical GRADE evidence profile below (Table 3).

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

Table 2

Summary of included studies: SSRIs for early prevention (<1 month).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (SSRIs for the prevention of PTSD in adults) are presented in Table 3.

Table 3

Summary clinical evidence profile: Escitalopram versus placebo for the early prevention (<1 month) of PTSD in adults.

See Appendix F for full GRADE tables.

Included studies

One study of anticonvulsants for the prevention of PTSD in adults was identified for full-text review, and this 1 RCT (N=48) compared gabapentin with placebo for the early prevention (intervention initiated within 1 month of traumatic event) of PTSD in adults (Stein 2007). This RCT had three arms and also compared gabapentin with propranolol (see other drugs section below).

Excluded studies

No studies on anticonvulsants were reviewed at full text and excluded.

Summary of clinical studies included in the evidence review

Table 4 provides a brief summary of the included study and evidence from this study is summarised in the clinical GRADE evidence profile below (Table 5).

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

Table 4

Summary of included studies: Anticonvulsants for early prevention (<1 month).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (anticonvulsants for the prevention of PTSD in adults) are presented in Table 5.

Table 5

Summary clinical evidence profile: Gabapentin versus placebo for the early prevention (<1 month) of PTSD in adults.

See Appendix F for full GRADE tables.

Included studies

Two studies of benzodiazepines for the prevention of PTSD in adults were identified for full-text review. Of these 2 studies, 1 RCT (N=22) was included in a single comparison for benzodiazepines (Mellman 2002). This RCT compared temazepam with placebo for the early prevention (intervention initiated within 1 month of traumatic event) of PTSD in adults.

Excluded studies

One study was reviewed at full text and excluded from this review because the study was unpublished (registered on clinical trials.gov and author contacted for full trial report but author confirmed that this study had never reached ‘operational stage’).

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 6 provides a brief summary of the included study and evidence from this study is summarised in the clinical GRADE evidence profile below (Table 7).

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

Table 6

Summary of included studies: Benzodiazepines for early prevention (<1 month).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (benzodiazepines for the prevention of PTSD in adults) are presented in Table 7.

Table 7

Summary clinical evidence profile: Temazepam versus placebo for the early prevention (<1 month) of PTSD in adults.

See Appendix F for full GRADE tables.

Included studies

Thirty-four studies of other drugs for the prevention of PTSD in adults were identified for full-text review. Of these 34 studies, 6 RCTs (N=354) were included. There were 5 comparisons for other drugs. 1 RCT had 3 arms and was included in 2 comparisons.

For the early prevention (intervention initiated within 1 month of traumatic event) of PTSD in adults, there were 4 relevant comparisons: 1 RCT (N=68) compared hydrocortisone with placebo (Delahanty 2013); 1 RCT (N=120) compared oxytocin with placebo (van Zuiden 2017); 3 RCTs (N=132) compared propranolol with placebo (Hoge 2012; Pitman 2002; Stein 2007); and 1 RCT (N=48) compared propranolol with gabapentin (Stein 2007).

For the delayed treatment (>3 months) of non-significant PTSD symptoms in adults, there was 1 relevant comparison: 1 RCT (N=34) compared prazosin with placebo (Germain 2012).

Excluded studies

Twenty-eight studies were reviewed at full text and excluded from this review. The most common reasons for exclusion were that the paper was a systematic review with no new useable data and any meta-analysis results not appropriate to extract, or the intervention was outside protocol.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 8 and BME – Black and minority ethnic; NR-Not reported; PTSD-Post-traumatic stress disorder.

Table 9 provide brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 10, Table 11, Table 12, Table 13 and Table 14).

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

Table 8

Summary of included studies: Other drugs for early prevention (<1 month).

Table 9

Summary of included studies: Other drugs for delayed treatment (>3 months) of non-significant PTSD symptoms.

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (other drugs for the prevention of PTSD in adults) are presented in Table 10, Table 11, Table 12, Table 13 and Table 14.

Table 10

Summary clinical evidence profile: Hydrocortisone versus placebo for the early prevention (<1 month) of PTSD in adults.

Table 11

Summary clinical evidence profile: Oxytocin versus placebo for the early prevention (<1 month) of PTSD in adults.

Table 12

Summary clinical evidence profile: Propranolol versus placebo for the early prevention (<1 month) of PTSD in adults.

Table 13

Summary clinical evidence profile: Propranolol versus gabapentin for the early prevention (<1 month) of PTSD in adults.

Table 14

Summary clinical evidence profile: Prazosin versus placebo for the delayed treatment (>3 months) of non-significant PTSD symptoms in adults.

See Appendix F for full GRADE tables.

Economic model

Economic modelling was not undertaken for this question because other topics were agreed as higher priorities for economic evaluation.

The outcomes that matter most

Critical outcomes were measures of PTSD symptom improvement on validated scales and prevention of PTSD (as measured by the number of people with a diagnosis or scoring above clinical threshold on a validated scale at endpoint or follow-up). Attrition from treatment (for any reason) was also considered an important outcome as a proxy for the acceptability of treatment, and discontinuation due to adverse events was considered as particularly important as an indicator of potential harm in terms of tolerability. The committee considered dissociative symptoms, personal/social/occupational functioning (including global functioning/functional impairment, sleeping or relationship difficulties, and quality of life), and symptoms of a coexisting condition (including anxiety and depression symptoms) as important but not critical outcomes. This distinction was based on the primacy of targeting the core PTSD symptoms, whilst acknowledging that broader symptom measures may be indicators of a general pattern of effect. Change scores were favoured over final scores as although in theory randomisation should balance out any differences at baseline, this assumption can be violated by small sample sizes. The committee also expressed a general preference for self-rated PTSD symptomatology, particularly for pharmacological interventions where the participant is likely to be blinded and may be less susceptible to bias than the study investigator(s). However, the committee discussed potential threats to blinding of the participant, for example in the context of side effects, and therefore triangulation with blinded clinician-rated outcome measures was also regarded as important.

The quality of the evidence

The evidence for this review was of moderate to very low quality, and of limited volume with most comparisons consisting of single studies with relatively few participants. There were also considerable gaps in the evidence, including widespread reporting of only endpoint data, very limited data reported for discontinuation due to adverse events (only reported by a single study), most comparisons including either self-rated or clinician-rated PTSD symptomatology measures but not both so triangulation not possible, relatively short-term follow-up periods, and less breadth in terms of effects on associated symptoms.

Consideration of clinical benefits and harms

The committee considered the evidence for harm associated with escitalopram, namely that patients treated with placebo appeared to show greater improvement in PTSD symptomatology than those receiving the drug. There were also higher rates of discontinuation in patients treated with escitalopram, hydrocortisone and propranolol than those treated with placebo. The committee also considered that providing a treatment that had no clinical benefit over placebo was harmful, as this prevents someone from accessing a treatment that could improve their condition. Such harms were evident in patients treated with an anticonvulsant, a benzodiazepine, or propranolol.

There was some limited evidence of benefit for hydrocortisone, oxytocin and prazosin, however this came from single studies and benefits were not observed consistently across outcomes. On this basis the committee did not consider a positive recommendation appropriate.

Taken together, the committee agreed that the potential harms outweighed the benefits for drug treatments in order to prevent PTSD.

Included studies

Eighty studies of SSRIs for the treatment of PTSD in adults were identified for full-text review. Of these 80 studies, 35 RCTs (N=5892) were included. Many of these 80 RCTs were three- or four-armed trials and as such were included in more than one comparison. There were 11 comparisons for SSRIs.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 20 RCTs (N=4547) compared SSRIs with placebo (Brady 2000; Connor et al. 1999b; Davidson 2001b; Davidson 2004a; Davidson 2006b/Davidson unpublished [one study reported across two papers]; Friedman 2007; GSK 29060 627 [unpublished data]; Li 2017; Marshall 2001; Marshall 2007; Martenyi 2002a; Martenyi 2007; Panahi 2011; Pfizer 588 [unpublished data]; Pfizer 589 [unpublished data]; SKB627, Bryson [unpublished data]; Tucker 2001; Tucker 2003/2004 [one study reported across two papers]; Van der Kolk 2007; Zohar 2002). 3 RCTs (N=292) compared SSRI augmentation of trauma-focused CBT with trauma-focused CBT alone or in addition to placebo (Buhmann 2016; Popiel 2015; Schneier 2012). 1 RCT (N=69) compared augmentation of non-trauma-focused cognitive therapy with sertraline relative to placebo (Hien 2015/Ruglass 2015 [one study reported across two papers]).1 RCT (N=50) compared paroxetine with amitriptyline (Celik 2011). 2 RCTs (N=153) compared an SSRI with paroxetine (Chung 2004/2005 [one study reported across two papers]; Seo 2010). 1 RCT (N=538) compared sertraline with venlafaxine (Davidson 2006b/Davidson unpublished [one study reported across two papers]). 1 RCT (N=207) compared augmentation of trauma-focused CBT with sertraline relative to augmentation with venlafaxine (Sonne 2016). 2 RCTs (N=97) compared sertraline with nefazodone (McRae 2004; Saygin 2002). 1 RCT (N=103) compared fluoxetine with moclobemide (Önder 2006), and the same RCT (N=103) also compared fluoxetine with tianeptine (Önder 2006). 1 RCT (N=40) compared fluvoxamine with reboxetine (Spivak et al. 2006). Finally, 3 RCTs (N=334) compared maintenance treatment with SSRIs relative to placebo (Davidson 2001a; Davidson 2005a; SKB650, Bryson [unpublished data]).

Sub-analyses were possible for the SSRIs versus placebo comparison, comparing effects by multiplicity of trauma and specific drug.

Excluded studies

Forty-five studies were reviewed at full text and excluded from this review. The most common reasons for exclusion were non-randomised group assignment, efficacy or safety data could not be extracted, or the paper was a systematic review with no new useable data and any meta-analysis results not appropriate to extract.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 16, BME, Black and Minority Ethnic; DSM, Diagnostic and Statistical Manual of mental disorders; GAD, generalised anxiety disorder; ICD, International Classification of Disease; MDD, major depressive disorder; NA, not applicable; NR, not reported; OCD, obsessive compulsive disorder; PTSD, post-traumatic stress disorder; SD, standard deviation; SSRIs, selective serotonin reuptake inhibitors;

¹ Brady 2000 ;

² Connor 1999b ;

³ Davidson 2001b ;

⁴ Davidson 2004a ;

⁵ Davidson 2006b/Davidson unpublished ;

⁶ Friedman 2007 ;

⁷GSK 29060 627;

⁸ Li 2017 ;

⁹ Marshall 2001 ;

¹⁰ Marshall 2007 ;

¹¹ Martenyi 2002a ;

¹² Martenyi 2007 ;

¹³ Panahi 2011 ;

¹⁴Pfizer 588;

¹⁵Pfizer 589;

¹⁶SKB627;

¹⁷ Tucker 2001 ;

¹⁸ Tucker 2003/2004 ;

¹⁹ van der Kolk 2007 ;

²⁰ Zohar 2002

Table 17, AUD, alcohol use disorders; BME, Black and Minority Ethnic; CBT, cognitive behavioural therapy; DSM, Diagnostic and Statistical Manual of mental disorders; ICD, International Classification of Disease; MDD, major depressive disorder; MVA, motor vehicle accidents; NA, not applicable; NR, not reported; PE, psychoeducation; PTSD, post-traumatic stress disorder; SD, standard deviation; SSRIs, selective serotonin reuptake inhibitors; SUD, substance use disorder; TF-CBT, trauma-focused-cognitive behavioural therapy

¹ Buhmann 2016 ;

² Popiel 2015 ;

³ Schneier 2012 ;

⁴ Chung 2004/2005 ;

⁵ Seo 2010

Table 18, and Table 19 provide brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 20, Table 21, Table 22, Table 23, Table 24, Table 25, Table 26, Table 27, Table 28, Table 29, Table 30 and Table 31).

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

Table 16

Summary of included studies: SSRIs for delayed treatment (>3 months)-part 1.

Table 17

Summary of included studies: SSRIs for delayed treatment (>3 months)-part 2.

Table 18

Summary of included studies: SSRIs for delayed treatment (>3 months)-part 3.

Table 19

Summary of included studies: SSRIs for delayed treatment (>3 months)-part 4.

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (SSRIs for the treatment of PTSD in adults) are presented in Table 20, Table 21, Table 22, Table 23, Table 24, Table 25, Table 26, Table 27, Table 28, Table 29, Table 30 and Table 31.

Table 20

Summary clinical evidence profile: SSRIs versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 21

Summary clinical evidence profile: Sertraline (+ non-trauma-focused cognitive therapy) versus placebo (+ non-trauma-focused cognitive therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 22

Summary clinical evidence profile: SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 23

Summary clinical evidence profile: Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 24

Summary clinical evidence profile: Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 25

Summary clinical evidence profile: Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 26

Summary clinical evidence profile: Fluvoxamine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 27

Summary clinical evidence profile: Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 28

Summary clinical evidence profile: Sertraline (+ trauma-focused CBT) versus venlafaxine (+ trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 29

Summary clinical evidence profile: Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 30

Summary clinical evidence profile: SSRIs versus placebo for maintenance treatment of PTSD symptoms in adults.

Table 31

Summary clinical evidence profile: SSRI + trauma-focused CBT versus (+/− placebo +) trauma-focused CBT for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Sensitivity and subgroup analysis

Sub-analysis of the comparison, SSRIs versus placebo for delayed treatment (>3 months) of clinically important symptoms/PTSD, by multiplicity of trauma revealed non-significant differences for PTSD outcomes and discontinuation due to adverse events. However, the test for subgroup differences on discontinuation due to any reason is statistically significant (Chi² = 6.50, p = 0.04), and suggests a relatively higher rate of discontinuation due to any reason for those who have experienced multiple incident index trauma (RR 1.52 [1.08, 2.15]) relative to those who have experienced single incident index trauma (RR 1.00 [0.89, 1.14]) or where the multiplicity of index trauma is unclear (RR 0.90 [0.73, 1.11]).

Sub-analysis by specific drug revealed non-significant differences for all PTSD outcomes and discontinuation (due to any reason or adverse events).

Included studies

Four studies of TCAs for the treatment of PTSD in adults were identified for full-text review. Of these 4 studies, 2 RCTs (N=106) were included in a single comparison for TCAs.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, both RCTs (N=106) compared TCAs with placebo (Davidson 1990; Kosten 1991).

Comparisons with SSRIs are presented in the SSRI section above.

Excluded studies

Two studies were reviewed at full text and excluded from this review because the paper was a secondary analysis of an RCT that had already been included, or due to small sample size (N<10 per arm).

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 32 provides brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profile below (Table 33).

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

Table 32

Summary of included studies: TCAs for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (TCAs for the treatment of PTSD in adults) are presented in Table 33.

Table 33

Summary clinical evidence profile: TCAs versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Included studies

Six studies of SNRIs for the treatment of PTSD in adults were identified for full-text review. Of these 6 studies, 2 RCTs (N=867) were included in a single comparison for SNRIs.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, both RCTs (N=867) compared SNRIs with placebo (Davidson 2006a/2008/2012 [one study reported across three papers]; Davidson 2006b/Davidson unpublished [one study reported across two papers]).

Comparisons with SSRIs are presented in the SSRI section above.

Excluded studies

Four studies were reviewed at full text and excluded from this review. The reasons for exclusion were non-randomised group assignment, conference abstract, or non-Englishlanguage paper.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 34 provides brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profile below (Table 35).

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

Table 34

Summary of included studies: SNRIs for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (SNRIs for the treatment of PTSD in adults) are presented in Table 35.

Table 35

Summary clinical evidence profile: Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Included studies

Five studies of MAOIs for the treatment of PTSD in adults were identified for full-text review. Of these 5 studies, 2 RCTs (N=105) were included. There were 2 comparisons for MAOIs, one of the RCTs was a three-armed trial and included in both comparisons.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 2 RCTs (N=105) compared MAOIs with placebo (Katz 1994; Kosten 1991), and 1 of these RCTs (N=60) compared phenelzine with imipramine.

Excluded studies

Three studies were reviewed at full text and excluded from this review because efficacy or safety data could not be extracted, or due to non-randomised group assignment or small sample size (N<10 per arm).

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 36 provides brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 37 and Table 38).

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

Table 36

Summary of included studies: MAOIs for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (MAOIs for the treatment of PTSD in adults) are presented in Table 37 and Table 38.

Table 37

Summary clinical evidence profile: MAOIs versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 38

Summary clinical evidence profile: Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Included studies

Ten studies of other antidepressant drugs for the treatment of PTSD in adults were identified for full-text review. Of these 10 studies, 3 RCTs (N=175) were included in 3 comparisons for other antidepressants drugs.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 1 RCT (N=42) compared nefazodone with placebo (Davis et al. 2004). 1 RCT (N=30) compared bupropion in addition to TAU with placebo in addition to TAU (Becker et al. 2007), and 1 RCT (N=103) compared moclobemide with tianeptine (Önder et al. 2006).

Excluded studies

Seven studies were reviewed at full text and excluded from this review. The most common reasons for exclusion were that the study was unpublished (registered on clinical trials.gov and author contacted for full trial report but not provided) or non-randomised group assignment.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 39 provides brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 40, Table 41 and Table 42).

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

Table 39

Summary of included studies: Other antidepressant drugs for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (other antidepressant drugs for the treatment of PTSD in adults) are presented in Table 40, Table 41 and Table 42.

Table 40

Summary clinical evidence profile: Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 41

Summary clinical evidence profile: Bupropion (+ TAU) versus placebo (+ TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 42

Summary clinical evidence profile: Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Included studies

Thirty-three studies of anticonvulsants for the treatment of PTSD in adults were identified for full-text review. Of these 33 studies, 6 RCTs (N=496) were included in 4 comparisons for anticonvulsants.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 3 RCTs (N=142) compared topiramate with placebo (Akuchekian & Amanat 2004; Tucker 2007; Yeh 2011/Mello 2008 [published study and trial protocol]). 1 RCT (N=85) compared divalproex with placebo (Davis 2008a), and 1 RCT (N=232) compared tiagabine with placebo (Davidson 2007). Finally, 1 RCT (N=37) compared augmentation of routine medications with pregabalin relative to placebo (Baniasadi 2014).

Excluded studies

Twenty-seven studies were reviewed at full text and excluded from this review. The most common reasons for exclusion was non-randomised group assignment.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 43 provide brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 44, Table 45, Table 46 and Table 47).

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

Table 43

Summary of included studies: Anticonvulsants for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (anticonvulsants for the treatment of PTSD in adults) are presented in Table 44, Table 45, Table 46 and Table 47.

Table 44

Summary clinical evidence profile: Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 45

Summary clinical evidence profile: Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 46

Summary clinical evidence profile: Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 47

Summary clinical evidence profile: Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Included studies

Twenty-nine studies of antipsychotics for the treatment of PTSD in adults were identified for full-text review. Of these 28 studies, 5 RCTs (N=505) were included in 2 comparisons for antipsychotics.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 3 RCTs (N=410) compared antipsychotic monotherapy with placebo (Carey 2012; Krystal 2011/2016 [one study reported across two papers]; Villarreal 2016). 2 RCTs (N=95) compared augmentation of routine medications with antipsychotics relative to placebo (Bartzokis 2005; Ramaswamy 2016).

Sub-analyses were possible for the antipsychotic monotherapy versus placebo comparison, comparing effects on different subscales of the Clinician-Administered PTSD Scale for DSM–IV (CAPS) and by multiplicity of trauma. Sub-analysis by specific drug was not meaningful as there was only 1 study in each subgroup.

Excluded studies

Twenty-four studies were reviewed at full text and excluded from this review. The most common reasons for exclusion were small sample size (N<10 per arm), the paper was a systematic review with no new useable data and any meta-analysis results not appropriate to extract, or the study was unpublished (registered on clinical trials.gov and author contacted for full trial report but not provided).

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 48 provide brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 49 and Table 50).

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

Table 48

Summary of included studies: Antipsychotics for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (antipsychotics for the treatment of PTSD in adults) are presented in Table 49 and Table 50.

Table 49

Summary clinical evidence profile: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 50

Summary clinical evidence profile: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Sensitivity and subgroup analysis

Sub-analysis of the comparison, antipsychotic monotherapy versus placebo for delayed treatment (>3 months) of clinically important symptoms/PTSD, by CAPS subscale revealed no significant differences in the effects across the CAPS-B (re-experiencing), CAPS-C (avoidance/numbing), and CAPS-D (hyperarousal) subscales. Sub-analyses by multiplicity of trauma also revealed non-significant differences in efficacy across PTSD outcomes and on discontinuation for those who had experienced multiple incident index trauma relative to those where multiplicity of trauma was unclear.

Included studies

Five studies of benzodiazepines for the treatment of PTSD in adults were identified for full-text review. Of these 5 studies, 1 RCT (N=156) was included, and had three-arms meaning there were 2 comparisons for benzodiazepines.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 1 RCT (N=156) compared the augmentation of virtual reality exposure therapy with alprazolam relative to placebo, and the same study also compared alprazolam augmentation with d-cycloserine augmentation (Rothbaum 2014/Norrholm 2016 [one study reported across two papers]).

Excluded studies

Four studies were reviewed at full text and excluded from this review. Reasons for exclusion were: small sample size (N<10 per arm); non-randomised group assignment; systematic review with no new useable data and any meta-analysis results not appropriate to extract; population outside scope (inoculation interventions for people who may be at risk of experiencing but have not experienced, a traumatic event).

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 51 provides a brief summary of the included study and evidence from this study is summarised in the clinical GRADE evidence profiles below (Table 52 and Table 53).

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

Table 51

Summary of included studies: Benzodiazepines for delayed treatment (>3 months).

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (benzodiazepines for the treatment of PTSD in adults) are presented in Table 52 and Table 53.

Table 52

Summary clinical evidence profile: Alprazolam (+ virtual reality exposure therapy) versus placebo (+ virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 53

Summary clinical evidence profile: Alprazolam (+ virtual reality exposure therapy) versus d-cycloserine (+ virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Included studies

One hundred and fourteen studies of other drugs for the treatment of PTSD in adults were identified for full-text review. Of these 114 studies, 12 RCTs (N=979) were included. One of these RCTs was included in more than one comparison (three-armed trial where each arm was relevant to this section of the review). There were 8 comparisons for other drugs.

There were no studies for early treatment (intervention initiated 1–3 months post-trauma) of PTSD symptoms.

For delayed treatment (intervention initiated more than 3 months post-trauma) of PTSD symptoms, 4 RCTs (N=542) compared prazosin (alone or in addition to TAU) with placebo (alone or in addition to TAU) (Ahmadpanah 2014; Petrakis 2016; Raskind 2007; Raskind 2018/Ventura 2007 [published paper and trial protocol]). 1 of these RCTs (N=102) also compared prazosin with hydroxyzine, and hydroxyzine with placebo (Ahmadpanah et al. 2014). 1 RCT (N=27) compared eszopiclone versus placebo (Pollack 2011). 1 RCT (N=41) compared augmentation of routine medications with propranolol relative to placebo (Mahabir et al. 2016), 1 RCT (N=24) compared augmentation of routine medications with rivastigmine relative to placebo (Ardani 2017), and 1 RCT (N=63) compared augmentation of routine medications with guanfacine relative to placebo (Neylan 2006). Finally, 4 RCTs (N=282) compared augmentation of exposure therapy with d-cycloserine relative to placebo (de Kleine et al. 2012/2014/2015 [one study reported across three papers]; Difede 2014/Difede 2008 [published paper and trial protocol]; Litz 2012; Rothbaum 2014/Norrholm 2016 [one study reported across two papers).

Excluded studies

Forty-five studies were reviewed at full text and excluded from this review. The most common reasons for exclusion were non-randomised group assignment, efficacy or safety data could not be extracted, or the paper was a systematic review with no new useable data and any meta-analysis results not appropriate to extract.

Studies not included in this review with reasons for their exclusions are provided in Appendix K.

Summary of clinical studies included in the evidence review

Table 54, BME, Black and Minority Ethnic; DSM, Diagnostic and Statistical Manual of mental disorders; ICD, International Classification of Disease; MDD, major depressive disorder; NR, not reported; PTSD, post-traumatic stress disorder; SD, standard deviation; SSRI, selective serotonin reuptake inhibitor; TAU, treatment as usual; TCA, tricyclic anti-depressants.

¹ Ahmadpanah 2014 ;

² Petrakis 2016 ;

³ Raskind 2007 ;

⁴ Raskind 2018/Ventura 2007

Table 55 and BME, Black and Minority Ethnic; DSM, Diagnostic and Statistical Manual of mental disorders; GAD, generalised anxiety disorder; ICD, International Classification of Disease; MINI, Mini-International Neuropsychiatric Interview; MDD, major depressive disorder; NR, not reported; PTSD, post-traumatic stress disorder; SSRI, selective serotonin reuptake inhibitor

Table 56 provide brief summaries of the included studies and evidence from these are summarised in the clinical GRADE evidence profiles below (Table 57, Table 58, Table 59, Table 60, Table 61, Table 62, Table 63 and Table 64).

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

Table 54

Summary of included studies: Other drugs for delayed treatment (>3 months)-part 1.

Table 55

Summary of included studies: Other drugs for delayed treatment (>3 months)-part 2.

Table 56

Summary of included studies: Other drugs for delayed treatment (>3 months)-part 3.

Quality assessment of clinical studies included in the evidence review

The clinical evidence profiles for this review (SSRIs for the treatment of PTSD in adults) are presented in Table 57, Table 58, Table 59, Table 60, Table 61, Table 62, Table 63 and Table 64.

Table 57

Summary clinical evidence profile: Prazosin (+/− TAU) versus placebo (+/− TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 58

Summary clinical evidence profile: Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 59

Summary clinical evidence profile: Hydroxyzine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 60

Summary clinical evidence profile: Eszopiclone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 61

Summary clinical evidence profile: Propranolol (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 62

Summary clinical evidence profile: Rivastigmine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 63

Summary clinical evidence profile: Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

Table 64

Summary clinical evidence profile: d-cycloserine (+ exposure therapy) versus placebo (+ exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults.

The outcomes that matter most

Critical outcomes were measures of PTSD symptom improvement on validated scales, remission (as defined as a loss of diagnosis or scoring below threshold on a validated scale), and response (as measured by an agreed percentage improvement in symptoms and/or by a dichotomous rating of much or very much improved). Attrition from treatment (for any reason) was also considered an important outcome as a proxy for the acceptability of treatment, and discontinuation due to adverse events was considered as particularly important as an indicator of potential harm in terms of tolerability. The committee considered dissociative symptoms, personal/social/occupational functioning (including global functioning/functional impairment, sleeping or relationship difficulties, and quality of life), and symptoms of a coexisting condition (including anxiety and depression symptoms) as important but not critical outcomes. This distinction was based on the primacy of targeting the core PTSD symptoms, whilst acknowledging that broader symptom measures may be indicators of a general pattern of effect. Change scores were favoured over final scores as although in theory randomisation should balance out any differences at baseline, this assumption can be violated by small sample sizes. The committee also expressed a general preference for self-rated PTSD symptomatology, particularly for pharmacological interventions where the participant is likely to be blinded and may be less susceptible to bias than the study investigator(s). However, the committee discussed potential threats to blinding of the participant, for example in the context of side effects, and therefore triangulation with blinded clinician-rated outcome measures was also regarded as important.

The quality of the evidence

With the exception of a few outcomes of moderate quality, all the evidence reviewed was of very low or low quality, reflecting the high risk of bias associated with the studies (including for instance, lack of/unclear blinding of outcome assessment), the small numbers in many trials and the imprecision of many of the results (in terms of both the width of the confidence intervals and the failure to meet the optimal information size), and the risk of publication bias due to funding from pharmaceutical companies. Moreover, there is very little follow-up data available meaning that the evidence pertains only to short-term effects.

Consideration of clinical benefits and harms

When developing the recommendations, the committee considered a number of factors including the relative strength of the evidence, the preference that service users may have for medication (or psychological interventions) and the adverse effects of medication.

The committee considered the short term and long-term harms associated with the side effects of medication including for the SSRIs drowsiness, nausea, insomnia, agitation, restlessness and sexual problems, for venlafaxine discontinuation symptoms, and for the antipsychotics concerns with weight gain and hyperlipidaemia and raised blood glucose. The committee took these factors into account in developing the recommendations, but were also mindful of the negative consequences of prolonged PTSD and associated symptoms, the potential to ameliorate functional impairment, and the need to facilitate patient choice where there is a clear preference for medication over psychological interventions. The committee agreed that the benefits of pharmacological interventions for symptom management could be outweighed by the potential harms.

The committee discussed the strength of the evidence for SSRIs in terms of the number of RCTs and participants, the triangulation of effects on PTSD symptomatology across self-rated and clinician-rated measures, and benefits on other important outcomes (including depression symptoms, dissociative symptoms, functional impairment/global functioning, and quality of life). Conversely, the size of effects are small (in most cases falling below the threshold for clinical importance), there is no follow-up data, and there is evidence for harm as measured by discontinuation due to adverse events. Taken together, the committee regarded the consistency of the benefits to warrant a recommendation for those who have a preference for medication over psychological interventions, however, based on the effect sizes and limitations of the evidence a ‘consider’ rather than ‘offer’ recommendation was regarded as appropriate. The committee considered the evidence on the effectiveness of different SSRIs. There is no evidence for significant differential efficacy of specific SSRIs (sertraline, fluoxetine and paroxetine), so the committee decided not to recommend specific drugs and agreed that individual prescribers should be able to decide which SSRI to use. However, the committee agreed that it would be helpful to include sertraline as an example because it is one of two drugs licensed in the UK for this indication and the other drug, paroxetine, is likely to be associated with discontinuation symptoms. The committee felt it was important that SSRIs were not considered as a first-line treatment for PTSD (except where a person expresses a preference for drug treatment) due to concern about side effects of SSRIs, evidence from the guideline NMA that suggests relatively larger effect sizes for all psychological interventions recommended relative to SSRIs (trauma-focused CBT, EMDR, non-trauma-focused CBT and self-help with support), and evidence from the guideline economic modelling that suggests that SSRIs are less cost-effective than EMDR, brief individual trauma-focused CBT or self-help with support.

The evidence suggests benefits of venlafaxine on PTSD outcomes (both self-rated and clinician-rated) and on other important outcomes (including depression symptoms, functional impairment/global functioning, and quality of life). In discussing the relative merits of SSRIs and venlafaxine, the committee noted that the evidence was weaker for venlafaxine than for SSRIs in terms of the number of RCTs and no evidence is available for direct or indirect comparisons of venlafaxine relative to psychological interventions. Conversely, the effect sizes are slightly larger for venlafaxine relative to SSRIs, there is no evidence for harm for venlafaxine (as measured by discontinuation due to adverse events), and there is limited evidence suggesting a small but statistically significant benefit of venlafaxine relative to sertraline. Taken together, the committee agreed that it was appropriate to offer a straight choice between SSRIs and venlafaxine, and given that the evidence for venlafaxine shares the same limitations as for SSRIs in terms of the lack of follow-up and modest effect sizes, a ‘consider’ recommendation was also appropriate here.

The committee discussed the evidence for antipsychotics that shows benefits (as monotherapy or augmentation of routine medications) on PTSD outcomes and associated symptoms (including anxiety and depression symptoms, functional impairment, and sleeping difficulties). The committee discussed whether benefits were limited to certain PTSD symptom domains, for instance effects on hyperarousal in the context of potentially sedative effects. However, examination of the sub-analysis of clinician-rated PTSD symptomatology by CAPS subscale did not reveal statistically significant differences between effects on re-experiencing, avoidance/numbing, or hyperarousal symptom domains. Based on limitations in the evidence, including a smaller number of RCTs than SSRIs or recommended psychological interventions, the restricted depth and breadth of evidence (for instance, no direct or indirect comparisons of antipsychotics relative to SSRIs or psychological interventions) and the lack of follow-up data, the committee agreed that a ‘consider’ rather than ‘offer’ recommendation was appropriate. The committee did not believe that antipsychotics should be considered as a first-line treatment for PTSD and recommended that they should only be considered as an adjunct to psychological therapies and only where symptoms have not responded to other drug or psychological treatments. The committee agreed that antipsychotics may be useful for symptom management where a person is experiencing significant functional impairment that may inhibit engagement with psychological treatment that targets core PTSD symptoms. The committee discussed whether people with PTSD who require symptom management with antipsychotics could be safely and effectively cared for within primary care services, and agreed that due to concerns about tolerability, antipsychotics should only be initiated in specialist services or after consultation with a specialist, and this treatment should be subject to regular specialist review.

Given the considerable evidence for psychological interventions and SSRIs, the committee considered it appropriate to set a relatively high bar for other interventions. There was limited evidence for neither significant benefits nor harms of mirtazapine (relative to SSRIs), SSRI augmentation of trauma-focused CBT (relative to trauma-focused CBT alone or with placebo), SSRIs as maintenance treatment for relapse prevention, nefazodone, bupropion, topiramate, divalproex, tiagabine, or augmentation of routine medications with propranolol, rivastigmine or guanfacine. For some interventions (such as TCAs, non-trauma-focused CBT augmentation with sertraline, trauma-focused CBT augmentation with d-cycloserine, augmentation of routine medications with pregbalin or prazosin, or treatment with phenelzine, eszopiclone or hydroxyzine alone), there is limited evidence for efficacy but the evidence base was considered too small to be confident that the benefits observed are true effects and thus a recommendation could not be supported. Finally, the committee discussed the evidence for alprazolam augmentation of virtual reality exposure therapy which shows non-significant benefit and potential harm in terms of less improvement in clinician-rated PTSD symptomatology. The committee discussed whether a negative recommendation should be made on the basis of this evidence and agreed that a negative recommendation was not appropriate given the weakness of the evidence base (a single RCT), and the fact that the negative effect is driven by greater improvement in the placebo arm but participants receiving alprazolam also showed improvement albeit to a lesser extent.

Cost effectiveness and resource use

Existing economic evidence suggested that SSRIs are cost-effective compared with pharmacological treatment as usual in adults with PTSD. The committee took this evidence into account but noted that this is only partially applicable to the UK and is characterised by potentially serious limitations. The committee also considered the results of the guideline base-case economic analysis of psychological interventions for the treatment of adults with clinically important PTSD symptoms, which included SSRIs as a treatment option. The analysis was overall characterised by minor limitations and its results were directly applicable to the NICE decision-making context, so the committee was confident to use its findings to support recommendations. The committee noted that, according to the results, SSRIs were less cost-effective than psychological interventions such as EMDR, brief individual trauma-focused CBT and self-help with support, but more cost-effective than other interventions such as IPT, counselling, non-trauma-focused CBT, present-cantered therapy and no treatment. The committee therefore decided to recommend more cost-effective psychological interventions as first-line treatment options, but also make a ‘consider’ recommendation for SSRIs as an option for people who have a preference for pharmacological treatment.

The committee noted the lack of economic evidence on venlafaxine, but took into account that effect sizes for venlafaxine were a little larger than for SSRIs and also that both venlafaxine and SSRIs are available in generic form and therefore their acquisition costs are low and not very different. Consequently, the committee concluded that venlafaxine was likely to be similarly cost-effective to SSRIs, which supported a ‘consider’ recommendation for venlafaxine as another pharmacological option for people who have a preference for pharmacological treatment.

The committee noted the lack of economic evidence on antipsychotics. They considered the effectiveness of antipsychotics in improving PTSD symptoms and the fact that they are available in generic form, and therefore their acquisition cost is low. On the other hand, they noted that people taking antipsychotics need to be treated by specialists and to have regular reviews and they acknowledged that this increases total antipsychotic treatment costs. Moreover, use of antipsychotics is associated with the development of side effects such as extrapyramidal symptoms and metabolic syndrome, the management of which incurs extra costs. Nevertheless, the committee expressed the view that the overall benefits for people with PTSD who would be suitable to receive antipsychotics would overweigh the costs associated with treatment and decided to make a ‘consider’ recommendation for antipsychotics, adjunct to psychological therapies, for symptom management of adults with PTSD who have not responded to other pharmacological or psychological treatment and who have disabling symptoms and behaviours. This recommendation is expected to entail modest resource implications as it is relevant to a sub-group of adults with PTSD. The committee expressed the view that restricting the recommendation for initiation and regular review of antipsychotics only by specialists is likely to reduce variation in the way antipsychotics are used in current practice. As regular review of antipsychotics is essential but might not be happening currently, this should also improve consistency across settings.

Overall, the committee anticipated that the recommendations on pharmacological interventions for the treatment of PTSD in adults will result in a small change in practice, as in the previous guideline pharmacological treatment was recommended as an option to be considered only for adults who could not start psychological therapy, did not want to start trauma-focused psychological therapy or who had gained little or no benefit from a course of trauma-focused psychological therapy.

The committee noted that only paroxetine and sertraline are currently licensed for the treatment of PTSD in the UK so the recommendations involve off-licence use.

Other factors the committee took into account

The service user representatives on the committee drew attention to the importance of side effect profiles of different interventions, and commented that pharmacological interventions, and particularly polypharmacy, can be re-traumatising due to their sedating effect. The committee discussed the impact of this experience on the power dynamics within a patient-clinician relationship. They also noted that different groups, such as younger adults and ex-military may be more susceptible to coercion. The committee noted that there is a tendency to use pharmacological interventions where the trauma is seen to be greater, or more complex, however in these instances they discussed the fact that it may be least helpful, and even counterproductive, to use these treatments at that point.

Escitalopram versus placebo for the early prevention (<1 month) of PTSD in adults

Figure 2. PTSD symptomatology clinician-rated (CAPS change score)

Figure 3. Depression symptoms (MADRS change score)

Figure 4. Functional impairment (SDS change score)

Figure 5. Discontinuation due to any reason (including adverse events)

Gabapentin versus placebo for the early prevention (<1 month) of PTSD in adults

Figure 6. PTSD/ASD symptomatology (ASDS endpoint score)

Figure 7. Diagnosis of PTSD at 3-month follow-up

Figure 8. Discontinuation due to any reason (including adverse events)

Temazepam versus placebo for the early prevention (<1 month) of PTSD in adults

Figure 9. PTSD symptomatology clinician-rated (CAPS change score); Clinically important PTSD symptoms at baseline

Figure 10. Diagnosis of PTSD at 1-month follow-up

Hydrocortisone versus placebo for the early prevention (<1 month) of PTSD in adults

Figure 11. PTSD symptomatology clinician-rated (CAPS endpoint score); Unclear severity of PTSD symptoms at baseline

Figure 12. Diagnosis of PTSD; Unclear severity of PTSD symptoms at baseline

Figure 13. Depression symptoms (CES-D endpoint score); Unclear severity of PTSD symptoms at baseline

Figure 14. Quality of life (SF-36 General health change score)

Figure 15. Discontinuation due to adverse events

Oxytocin versus placebo for the early prevention (<1 month) of PTSD in adults

Figure 16. PTSD symptomatology self-rated (IES-R change score); Subthreshold symptoms (below threshold but ≥50% maximum score on scale) at baseline

Figure 17. PTSD symptomatology clinician-rated (CAPS change score); Subthreshold symptoms (below threshold but ≥50% maximum score on scale) at baseline

Figure 18. Anxiety symptoms (HADS-A change score); Subthreshold symptoms (below threshold but ≥50% maximum score on scale) at baseline

Figure 19. Depression symptoms (HADS-D change score); Subthreshold symptoms (below threshold but ≥50% maximum score on scale) at baseline

Figure 20. Discontinuation due to any reason (including adverse events)

Propranolol versus placebo for the early prevention (<1 month) of PTSD in adults

Figure 21. PTSD/ASD symptomatology self-rated (ASDS endpoint score)

Figure 22. PTSD symptomatology clinician-rated at endpoint (CAPS endpoint score)

Figure 23. PTSD symptomatology clinician-rated at endpoint (CAPS endpoint score)

Figure 24. PTSD symptomatology clinician-rated at 2-month follow-up (CAPS endpoint score)

Figure 25. Diagnosis of PTSD at endpoint

Figure 26. Diagnosis of PTSD at 2–3 month follow-up

Figure 27. Discontinuation due to any reason

Propranolol versus gabapentin for the early prevention (<1 month) of PTSD in adults

Figure 28. PTSD/ASD symptomatology self-rated (ASDS endpoint score)

Figure 29. Diagnosis of PTSD at 3-month follow-up

Figure 30. Discontinuation for any reason (including adverse events)

Prazosin versus placebo for the delayed treatment (>3 months) of non-significant PTSD symptoms in adults

Figure 31. PTSD symptomatology self-rated (PCL change score); Non-significant PTSD symptoms at baseline

Figure 32. Anxiety symptoms (BAI change score); Non-significant PTSD symptoms at baseline

Figure 33. Depression symptoms (BDI change score); Non-significant PTSD symptoms at baseline

Figure 34. Functional impairment (SDS change score); Non-significant PTSD symptoms at baseline

Figure 35. Sleeping difficulties (PSQI change score); Non-significant PTSD symptoms at baseline

Figure 36. Discontinuation due to any reason (including adverse events)

Figure 37. Discontinuation due to adverse events

SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 38. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS/IES-R change score)

Figure 39. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS/SI–PTSD change score)

Figure 40. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission clinician-rated (number of people scoring <20 on CAPS/no longer meeting diagnostic criteria for PTSD)

Figure 41. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission self-rated (number of people scoring <18 on DTS)

Figure 42. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥30% improvement on CAPS or IES-R/≥50% improvement on TOP-8 and/or CGI-I much or very much improved)

Figure 43. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 44. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D/MADRS/BDI/BDI-II change score)

Figure 45. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Dissociative symptoms (DES change score)

Figure 46. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 47. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Global functioning (GAF change score)

Figure 48. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (Q-LES-Q-SF change score)

Figure 49. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (PSQI change score)

Figure 50. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Relationship difficulties (IIP change score)

Figure 51. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 52. SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Sertraline (+ non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 68. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score); Unclear multiplicity of index trauma

Figure 69. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing improvement of at least 15 points on CAPS); Unclear multiplicity of index trauma

Figure 70. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Alcohol use: Number of heavy drinking days in the past 7 days (TLFB HDD; ≥5 drinks/day for men and ≥4 drinks/day for women; Change score); Unclear multiplicity of index trauma

Figure 71. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Alcohol use: Drinks per drinking day (TLFB DDD; change score); Unclear multiplicity of index trauma

Figure 72. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Alcohol use: Number of participants abstinent from alcohol (in the prior 7 days; TLFB); Unclear multiplicity of index trauma

Figure 73. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 74. Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 75. SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 76. SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥30% improvement on CAPS)

Figure 77. SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D/BDI-II change score)

Figure 78. SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 79. SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 80. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 81. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS/TOP-8 change score)

Figure 82. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 83. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (MADRS change score)

Figure 84. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 85. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (PSQI change score)

Figure 86. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 87. Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 88. Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 89. Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing >50% improvement on CAPS)

Figure 90. Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 91. Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 92. Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 93. Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing >50% improvement on CAPS)

Figure 94. Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 95. Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Fluoxetine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 96. Fluoxetine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 97. Fluoxetine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 98. Fluoxetine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 99. Fluoxetine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Sertraline versus venlafaxine for treatment of PTSD for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 100. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 101. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 102. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people scoring <20 on CAPS)

Figure 103. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 104. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 105. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Global functioning (GAF change score)

Figure 106. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (Q-LES-Q-SF change score)

Figure 107. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 108. Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Sertraline (+ trauma-focused CBT) versus venlafaxine (+ trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 109. Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (HTQ change score)

Figure 110. Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 111. Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 112. Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 113. Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (WHO-5 change score)

Figure 114. Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 115. Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 116. Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥30% improvement on CAPS & CGI-I much or very much improved)

Figure 117. Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (BAI change score)

Figure 118. Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (BDI change score)

Figure 119. Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 120. Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

SSRI versus placebo for maintenance treatment of PTSD symptoms

Figure 121. SSRI versus placebo for maintenance treatment of PTSD symptoms: Relapse

Figure 122. SSRI versus placebo for maintenance treatment of PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 123. SSRI versus placebo for maintenance treatment of PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 124. SSRI versus placebo for maintenance treatment of PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 125. SSRI versus placebo for maintenance treatment of PTSD symptoms: Quality of life (Q-LES-Q-SF change score)

Figure 126. SSRI versus placebo for maintenance treatment of PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 127. SSRI versus placebo for maintenance treatment of PTSD symptoms: Discontinuation due to adverse events

SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 128. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at endpoint (HTQ/PDS change score)

Figure 129. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at 1-year follow-up (PDS change score)

Figure 130. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS/SI–PTSD change score)

Figure 131. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people no longer meeting diagnostic criteria for PTSD/scoring ≤20 on CAPS & CGI-I score=1)

Figure 132. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people rated as ‘much’ or ‘very much’ improved on CGI-I)

Figure 133. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms at endpoint (HAM-A/STAI State change score)

Figure 134. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms at 1-year follow-up (STAI State change score)

Figure 135. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms at endpoint (HAM-D/BDI-II change score)

Figure 136. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms at 1-year follow-up (BDI-II change score)

Figure 137. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 138. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (WHO-5 change score)

Figure 139. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 140. SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 141. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (IES change score); Multiple incident index trauma

Figure 142. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (SI–PTSD change score); Multiple incident index trauma

Figure 143. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥50% improvement on SI–PTSD/rated as ‘much or very much improved’ on CGI-I); Multiple incident index trauma

Figure 144. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A/CAS change score); Multiple incident index trauma

Figure 145. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score); Multiple incident index trauma

Figure 146. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events); Multiple incident index trauma

Figure 147. TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events; Multiple incident index trauma

Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 148. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomology at endpoint (CAPS)

Figure 149. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Symptoms of/recovery from depression at endpoint (HAM-D 17)

Figure 150. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Global functioning at endpoint (GAF)

Figure 151. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life at endpoint (Quality of Life Enjoyment and Life Satisfaction Short Form)

Figure 152. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment at endpoint (Sheehan Disability Scale)

Figure 153. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse effects) at endpoint

Figure 154. Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse effects

MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 155. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (IES change score); Multiple incident index trauma

Figure 156. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score); Single incident index trauma

Figure 157. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people no longer meeting diagnostic criteria for PTSD); Single incident index trauma

Figure 158. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people rated as ‘much’ or ‘very much’ improved on CGI-I); Multiple incident index trauma

Figure 159. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (CAS change score); Multiple incident index trauma

Figure 160. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score); Multiple incident index trauma

Figure 161. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 162. MAOI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events; Multiple incident index trauma

Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 163. Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (IES change score)

Figure 164. Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people rated as ‘much’ or ‘very much’ improved on CGI-I)

Figure 165. Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (CAS change score)

Figure 166. Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 167. Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 168. Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 169. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (PCL change score)

Figure 170. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 171. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥30% improvement on CAPS)

Figure 172. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 173. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Dissociative symptoms (CADSS change score)

Figure 174. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 175. Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Bupropion (+TAU) versus placebo (+TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 176. Bupropion (+TAU) versus placebo (+TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 177. Bupropion (+TAU) versus placebo (+TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (BDI change score)

Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 178. Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults: PTSD symptomatology clinician-rated (CAPS change score)

Figure 179. Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults: Response (number of people showing >50% improvement on CAPS)

Figure 180. Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults: Discontinuation due to any reason (including adverse events)

Figure 181. Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults: Discontinuation due to adverse events

Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 182. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 183. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 184. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥30% improvement on CAPS)

Figure 185. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 186. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D/BDI change score)

Figure 187. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 188. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 189. Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 190. Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 191. Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 192. Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (MADRS change score)

Figure 193. Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 194. Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 195. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 196. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people rated as ‘much’ or ‘very much’ improved on CGI-I)

Figure 197. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people scoring <20 on CAPS)

Figure 198. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (MADRS change score)

Figure 199. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 200. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 201. Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 202. Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (PCL change score)

Figure 203. Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 204. Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 205. Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (Spitzer Quality of Life Index change score)

Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 206. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 207. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 208. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people scoring <50 on CAPS)

Figure 209. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing >50% improvement on CAPS)

Figure 210. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 211. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (MADRS/HAM-D change score)

Figure 212. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 213. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (BLSI change score)

Figure 214. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (PSQI change score)

Figure 215. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 216. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Figure 217. Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomology by subscale

Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 218. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (DTS change score)

Figure 219. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 220. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people scoring <50 on CAPS)

Figure 221. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing >50% improvement on CAPS)

Figure 222. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 223. Sub-analysis by specific intervention: Antipsychotic monotherapy versus lacebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (MADRS/HAM-D change score)

Figure 224. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Functional impairment (SDS change score)

Figure 225. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (BLSI change score)

Figure 226. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (PSQI change score)

Figure 227. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 228. Sub-analysis by specific intervention: Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication)

Figure 229. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 230. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥20/50% improvement on CAPS)

Figure 231. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 232. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 233. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 234. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Figure 235. Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medication) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomology by subscale

Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 236. Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 237. Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people showing ≥20% improvement on CAPS)

Figure 238. Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms (HAM-A change score)

Figure 239. Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 240. Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 241. Sub-analysis by specific intervention: Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) of for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Alprazolam (+ virtual reality exposure therapy) versus placebo (+ virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms

Figure 242. Alprazolam (+virtual reality exposure therapy) versus placebo (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-report (PSS-SR change score); Multiple incident index trauma

Figure 243. Alprazolam (+virtual reality exposure therapy) versus placebo (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score); Multiple incident index trauma

Figure 244. Alprazolam (+virtual reality exposure therapy) versus placebo (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people no longer meeting diagnostic criteria for PTSD); Multiple incident index trauma

Figure 245. Alprazolam (+virtual reality exposure therapy) versus placebo (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Alprazolam (+ virtual reality exposure therapy) versus d-cycloserine (+ virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 246. Alprazolam (+virtual reality exposure therapy) versus d-cycloserine (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-report (PSS-SR change score); Multiple incident index trauma

Figure 247. Alprazolam (+virtual reality exposure therapy) versus d-cycloserine (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score); Multiple incident index trauma

Figure 248. Alprazolam (+virtual reality exposure therapy) versus d-cycloserine (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission (number of people no longer meeting diagnostic criteria for PTSD); Multiple incident index trauma

Figure 249. Alprazolam (+virtual reality exposure therapy) versus d-cycloserine (+virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Prazosin (±TAU) versus placebo (± TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 250. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at endpoint (PCL change score)

Figure 251. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS/MINI change score)

Figure 252. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response (number of people rated as ‘much’ or ‘very much’ improved on CGI-I)

Figure 253. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms at endpoint (BDI/HAM-D/PHQ-9 change score)

Figure 254. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Alcohol use (TLFB): Number of participants abstinent from alcohol during the trial

Figure 255. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Alcohol craving/consumption (OCDS/AUDIT-C change score)

Figure 256. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties at endpoint (PSQI change score)

Figure 257. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (QOLI change score)

Figure 258. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 259. Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 260. Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (MINI change score)

Figure 261. Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (PSQI change score)

Figure 262. Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 263. Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Hydroxyzine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 264. Hydroxyzine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (MINI change score)

Figure 265. Hydroxyzine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (PSQI change score)

Eszopiclone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 266. Eszopiclone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 267. Eszopiclone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Propranolol (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 268. Propranolol (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (IES-R change score)

Rivastigmine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 269. Rivastigmine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (PCL change score)

Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 270. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated (IES-R change score)

Figure 271. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated (CAPS change score)

Figure 272. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms (HAM-D change score)

Figure 273. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Quality of life (QOLI change score)

Figure 274. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Sleeping difficulties (Sleep Quality Index change score)

Figure 275. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 276. Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

D-cycloserine (+ exposure therapy) versus placebo (+ exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Figure 277. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at endpoint (PCL/PSS-SR change score)

Figure 278. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at 3-month follow-up (PSS-SR change score)

Figure 279. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at 6-month follow-up (PSS-SR change score)

Figure 280. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology self-rated at 1-year follow-up (PSS-SR change score)

Figure 281. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated at endpoint (CAPS change score)

Figure 282. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated at 3-month follow-up (CAPS change score)

Figure 283. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated at 6-month follow-up (CAPS change score)

Figure 284. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: PTSD symptomatology clinician-rated at 1-year follow-up (CAPS change score)

Figure 285. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission at endpoint (number of people scoring <20 on CAPS/no longer meeting diagnostic criteria)

Figure 286. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission at 3-month follow-up (number of people scoring <20 on CAPS/no longer meeting diagnostic criteria)

Figure 287. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission at 6-month follow-up (number of people scoring <20 on CAPS/no longer meeting diagnostic criteria)

Figure 288. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Remission at 1-year follow-up (number of people no longer meeting diagnostic criteria)

Figure 289. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response at endpoint (number of people showing improvement of at least 10 points on CAPS)

Figure 290. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Response at 3-month follow-up (number of people showing improvement of at least 10 points on CAPS)

Figure 291. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms at endpoint (STAI State change score)

Figure 292. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Anxiety symptoms at 3-month follow-up (STAI State change score)

Figure 293. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms at endpoint (BDI/BDI-II change score)

Figure 294. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Depression symptoms at 3-month follow-up (BDI change score)

Figure 295. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to any reason (including adverse events)

Figure 296. D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms: Discontinuation due to adverse events

Escitalopram versus placebo for the early prevention (<1 month) of PTSD in adults

Table

1/12 (8.3%)

Gabapentin versus placebo for the early prevention (<1 month) of PTSD in adults

Table

6/14 (42.9%)

Temazepam versus placebo for the early prevention (<1 month) of PTSD in adults

Table

6/11 (54.5%)

Hydrocortisone versus placebo for the early prevention (<1 month) of PTSD in adults

Table

2/24 (8.3%)

Oxytocin versus placebo for the early prevention (<1 month) of PTSD in adults

Table

21/62 (33.9%)

Propranolol versus placebo for the early prevention (<1 month) of PTSD in adults

Table

15/40 (37.5%)

Propranolol versus gabapentin for the early prevention (<1 month) of PTSD in adults

Table

8/17 (47.1%)

Prazosin versus placebo for the delayed treatment (>3 months) of non-significant PTSD symptoms in adults

Table

5/18 (27.8%)

SSRI versus placebo

SSRI versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

262/880 (29.8%)

Sertraline (+non-trauma-focused cognitive therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

25/32 (78.1%)

SSRI versus other antidepressants

SSRI versus mirtazapine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

51/75 (68%)

Sertraline versus nefazodone for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

6/49 (12.2%)

Fluoxetine versus moclobemide for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

29/38 (76.3%)

Fluoxetine versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

29/38 (76.3%)

Fluvoxamine versus reboxetine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

3/20 (15%)

SSRI versus SNRI

Sertraline versus venlafaxine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

42/173 (24.3%)

Sertraline (+trauma-focused CBT) versus venlafaxine (+trauma-focused CBT) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

21/109 (19.3%)

SSRI versus TCA

Paroxetine versus amitriptyline for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

7/25 (28%)

SSRI versus placebo for maintenance treatment of PTSD symptoms in adults

Table

38/156 (24.4%)

SSRI versus psychological therapies

SSRI + trauma-focused CBT versus trauma-focused CBT (±placebo) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

28/76 (36.8%)

Antidepressants: Tricyclic antidepressants (TCAs)

TCA versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

21/48 (43.8%)

Antidepressants: Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Venlafaxine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

136/340 (40%)

Antidepressants: Monoamine-oxidase inhibitors (MAOIs)

MAOI versus placebo

Table

12/35 (34.3%)

Phenelzine versus imipramine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

13/19 (68.4%)

Antidepressants: Other antidepressants

Nefazodone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

9/27 (33.3%)

Bupropion (+TAU) versus placebo (+TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

BDI, Beck Depression Inventory; CI, confidence interval; DTS, Davidson Trauma Scale; PTSD, post-traumatic stress disorder; TAU, treatment as usual; SMD, standard mean difference

Moclobemide versus tianeptine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

22/35 (62.9%)

Anticonvulsants

Topiramate versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

14/17 (82.4%)

Divalproex versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

10/44 (22.7%)

Tiagabine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

51/116 (44%)

Pregabalin (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

0/18 (0%)

Antipsychotics

Antipsychotic monotherapy versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

10/14 (71.4%)

Antipsychotic (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

12/48 (25%)

Benzodiazepines

Alprazolam (+virtual reality exposure therapy) versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

9/50 (18%)

Alprazolam (+ virtual reality exposure therapy) versus d-cycloserine (+ virtual reality exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

9/50 (18%)

Other drugs: Prazosin

Prazosin (±TAU) versus placebo (±TAU) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

12/17 (70.6%)

Prazosin versus hydroxyzine for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

2/35 (5.7%)

Other drugs: Hydroxyzine

Hydroxyzine versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

0/34 (0%)

Other drugs: Eszopiclone

Eszopiclone versus placebo for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

1/13 (7.7%)

Other drugs: Propranolol

Propranolol (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

CI, confidence interval; IES-R, Impact of Event Scale-Revised; PTSD, post-traumatic stress disorder; SMD, standard mean difference

Other drugs: Rivastigmine

Rivastigmine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

CI, confidence interval; PCL, PTSD Checklist for DSM-5; PTSD, post-traumatic stress disorder; SMD, standard mean difference

Other drugs: Guanfacine

Guanfacine (augmentation of routine medications) versus placebo (augmentation of routine medications) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

6/29 (20.7%)

Other drugs: D-cycloserine

D-cycloserine (+exposure therapy) versus placebo (+exposure therapy) for the delayed treatment (>3 months) of clinically important PTSD symptoms in adults

Table

23/99 (23.2%)

Antidepressants: Selective serotonin reuptake inhibitors (SSRIs)

Table

Benzodiazepines

Table

Other drugs

Table

Antidepressants: Selective serotonin reuptake inhibitors (SSRIs)

Table

Antidepressants: Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Table

Antidepressants: Tricyclic antidepressants (TCAs)

Table

Antidepressants: Monoamine-oxidase inhibitors (MAOIs)

Table

Antidepressants: Other antidepressants

Table

Anticonvulsants

Table

Antipsychotics

Table

Benzodiazepines

Table

Other drugs

Table