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<meta name="keywords" content="CN176769, amitriptyline response, cyp2c19, cyp2d6, elavil response, sign or symptom, autosomal dominant, autosomal recessive, birth defects, chromosomal disease, chromosome, clinical features, clinical findings, clinical genetics, clinical recommendations, clinvar, congenital chromosomal disease, consumer genetic resources, cytogenetic location, disease characteristics, disease definitions, disease descriptions, disease ontology, disease synonyms, disease vocabulary, dysmorphology, entrez, familial disease, gene, gene-disease relationship, genereviews, genetic disease, genetic disorder, genetic terminology, genetic testing registry, genetics home reference, genomic disease, gtr, hereditary disease, heritable disease, hpo, human phenotype ontology, inherited disease, management guidelines, maternal inheritance, medgen, medical genetics, medical subject headings, mesh, mitochondrial inheritance, mode of inheritance, national center for biotechnology information, national institutes of health, national library of medicine, ncbi, nih, nlm, omim, ordo, orphanet, paternal inheritance, phenome, position statements, professional practice guidelines, rare disease, reference sequence, refseq, snomed ct, syndrome, undiagnosed diseases, x-linked recessive" /><meta name="description" content="Amitriptyline is a tricyclic that can be identified by the tertiary amine in its chemical structure. Tricyclics are commonly prescribed for psychological disorders and pain management. Genetic variants in both cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) may affect treatment success of amitriptyline or other tricyclics with the tertiary amine functional group. Patients with poor metabolizer variants of either CYP2D6 or CYP2C19 may require reductions in dose or alternative agents in order to circumvent common adverse anticholinergic, central nervous system, or cardiac effects. Guidelines regarding the use of pharmacogenomic tests in dosing for amitriptyline and other tricyclics have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website." /><meta name="robots" content="index,nofollow,noarchive" />
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<!--
|
||
UID=500846
|
||
ConceptID=CN176769
|
||
-->
|
||
<!--imgCountBooks = 0--><h1 class="medgenTitle"><div class="MedGenTitleText">Amitriptyline response</div></h1><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>500846</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier assigned by MedGen (starting with CN) for terms that cannot be identified in NLM's Unified Medical Language system (UMLS) Click for more information."><span class="highlight" style="background-color:">CN176769</span></a></dd><dt><span class="dotprefix"> •</span></dt><dd>Sign or Symptom</dd></dl></div></div><table class="medgenTable"><tbody><tr><td>Synonym:</td>
|
||
<td>Elavil response</td></tr>
|
||
<tr><td>Drug:</td>
|
||
<td>
|
||
<div class="divPopper rprt" id="drug_1486"><div><strong>Amitriptyline</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>1486</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS) Click for more information.">C0002600</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Pharmacologic Substance</dd></dl></div></div></div>
|
||
<div class="spaceAbove">A derivative of dibenzocycloheptadiene and a tricyclic antidepressant. Amitriptyline inhibits the re-uptake of norepinephrine and serotonin by the presynaptic neuronal membrane in the central nervous system (CNS), thereby increasing the synaptic concentration of norepinephrine and serotonin. Due to constant stimulation to these receptors, amitriptyline may produce a downregulation of adrenergic and serotonin receptors, which may contribute to the antidepressant activity. [from NCI]</div></div>
|
||
<div class="hangingIndent"><a title="click for more information" class="jig-ncbipopper" href="#drug_1486" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Amitriptyline</a></div></td></tr>
|
||
<tr><td colspan="2" class="small"> </td></tr><tr><td><a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#target-gene-loc">Genes (locations):<img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a><div class="display-none" id="target-gene-loc">
|
||
Gene(s) directly associated with<br />
|
||
this condition or phenotype.</div></td>
|
||
<td><a target="_blank" title="CYP2C19 - ID: 1557 - NCBI Gene" href="/gene/1557" class="medgenPMinfo">CYP2C19</a> (10q23.33); <a target="_blank" title="CYP2D6 - ID: 1565 - NCBI Gene" href="/gene/1565" class="medgenPMinfo">CYP2D6</a> (22q13.2)</td></tr>
|
||
</tbody></table></div><div class="rprt-body jig-ncbiinpagenav" data-jigconfig="smoothScroll: false, gotoTopLink: true, gotoTopLinkText: '', gotoTopLinkAttrs: {'title': 'Go to the top of the page'},allHeadingLevels: ['h1'], topOfPageTOC: true, tocId: 'my-toc'"><div id="rprt-tabs-1" class="rprt-tab"><div id="tb-termsProp-1"><div class="leftCol mgCol"><div>
|
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<div class="portlet mgSection" id="ID_100">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Definition">Definition</h1><a sid="100" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln">Amitriptyline is a tricyclic that can be identified by the tertiary amine in its chemical structure. Tricyclics are commonly prescribed for psychological disorders and pain management. Genetic variants in both cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) may affect treatment success of amitriptyline or other tricyclics with the tertiary amine functional group. Patients with poor metabolizer variants of either CYP2D6 or CYP2C19 may require reductions in dose or alternative agents in order to circumvent common adverse anticholinergic, central nervous system, or cardiac effects. Guidelines regarding the use of pharmacogenomic tests in dosing for amitriptyline and other tricyclics have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from <a title="The Pharmacogenomics Knowledge Base" href="http://www.pharmgkb.org" class="defSource" target="_blank">PharmGKB</a>]</div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_117">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Additional_description">Additional description</h1><a sid="117" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><div class="mgSection"><strong>From Medical Genetics Summaries</strong><br />Amitriptyline is a tricyclic antidepressant used in the treatment of several psychiatric disorders, including major depression, obsessive-compulsive disorder, panic attacks, generalized anxiety disorder, post-traumatic stress disorder, and bulimia. Amitriptyline also has different off-label uses, including migraine prevention, neuropathic pain management, fibromyalgia, and enuresis (bedwetting). Tricyclic antidepressants (TCAs) primarily mediate their therapeutic effect by inhibiting the reuptake of both serotonin and norepinephrine, leaving more neurotransmitter in the synaptic cleft stimulating the neuron. Because tricyclics can also block different receptors (H1 histamine, alpha 1 α1-adrenergic, and muscarinic receptors), side effects are common. As such, more specific selective serotonin reuptake inhibitors (SSRIs) have largely replaced the use of them. However, TCAs still have an important use in specific types of depression and other conditions. Amitriptyline is metabolized mainly via CYP2C19 and CYP2D6 pathways. Metabolism by CYP2C19 results in active metabolites, including nortriptyline, which is also a tricyclic antidepressant. Metabolism catalyzed by CYP2D6 results in the formation of the less active 10-hydroxy metabolite. Individuals who are “CYP2D6 ultrarapid metabolizers” carry more than two normal function alleles (i.e., multiple copies), whereas “CYP2C19 ultrarapid metabolizers” carry two increased function alleles. Individuals who are CYP2D6 or CYP2C19 “poor metabolizers” carry two no function alleles for CYP2D6 or CYP2C19, respectively. The FDA-approved drug label for amitriptyline states that CYP2D6 poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses. The FDA recommendations also include monitoring tricyclic antidepressant plasma levels whenever a tricyclic antidepressant is going to be co-administered with another drug known to be an inhibitor of CYP2D6. In 2016, the Clinical Pharmacogenetics Implementation Consortium (CPIC) made dosing recommendations for tricyclic antidepressants based on CYP2C19 and CYP2D6 genotypes. For CYP2D6 ultrarapid metabolizers, CPIC recommends avoiding the use of a tricyclic due to the potential lack of efficacy, and to consider an alternative drug not metabolized by CYP2D6. If a TCA is still warranted, CPIC recommends considering titrating the TCA to a higher target dose (compared to normal metabolizers) and using therapeutic drug monitoring to guide dose adjustments. For CYP2D6 intermediate metabolizers, CPIC recommends considering a 25% reduction of the starting dose, and for CYP2D6 poor metabolizers, to avoid the use of tricyclics because of the potential for side effects. If a tricyclic is still warranted for CYP2D6 poor metabolizers, CPIC recommends considering a 50% reduction of the starting dose while monitoring drug plasma concentrations to avoid side effects. For CYP2C19 ultrarapid metabolizers, CPIC recommends avoiding the use of tertiary amines (e.g., amitriptyline) due to the potential for a sub-optimal response, and to consider an alternative drug not metabolized by CYP2C19, such as the secondary amines nortriptyline or desipramine. For CYP2C19 poor metabolizers, CPIC recommends avoiding tertiary amine use due to the potential for sub-optimal response, and to consider an alternative drug not metabolized by CYP2C19. If a tertiary amine is still warranted for CYP2C19 poor metabolizers, CPIC recommends considering a 50% reduction of the starting dose while monitoring drug plasma concentrations while monitoring plasma concentrations to avoid side effects. <a target="_blank" href="https://www.ncbi.nlm.nih.gov/books/NBK425165">https://www.ncbi.nlm.nih.gov/books/NBK425165</a></div></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_105">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Professional_guidelines">Professional guidelines</h1><a sid="105" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><h3 class="subhead">PubMed<a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#guidelinesHelpPM"><img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a></h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/38394496">Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Haki M,
|
||
Al-Biati HA,
|
||
Al-Tameemi ZS,
|
||
Ali IS,
|
||
Al-Hussaniy HA</span><br />
|
||
<span class="medgenPMjournal">Medicine (Baltimore)</span>
|
||
2024 Feb 23;103(8):e37297.
|
||
doi: 10.1097/MD.0000000000037297.
|
||
<span class="bold">PMID: </span><a href="/pubmed/38394496" target="_blank">38394496</a><a href="/pmc/articles/PMC10883637" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/38015216">Obesity Management in Adults: A Review.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Elmaleh-Sachs A,
|
||
Schwartz JL,
|
||
Bramante CT,
|
||
Nicklas JM,
|
||
Gudzune KA,
|
||
Jay M</span><br />
|
||
<span class="medgenPMjournal">JAMA</span>
|
||
2023 Nov 28;330(20):2000-2015.
|
||
doi: 10.1001/jama.2023.19897.
|
||
<span class="bold">PMID: </span><a href="/pubmed/38015216" target="_blank">38015216</a><a href="/pmc/articles/PMC11325826" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/29477251">Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Cipriani A,
|
||
Furukawa TA,
|
||
Salanti G,
|
||
Chaimani A,
|
||
Atkinson LZ,
|
||
Ogawa Y,
|
||
Leucht S,
|
||
Ruhe HG,
|
||
Turner EH,
|
||
Higgins JPT,
|
||
Egger M,
|
||
Takeshima N,
|
||
Hayasaka Y,
|
||
Imai H,
|
||
Shinohara K,
|
||
Tajika A,
|
||
Ioannidis JPA,
|
||
Geddes JR</span><br />
|
||
<span class="medgenPMjournal">Lancet</span>
|
||
2018 Apr 7;391(10128):1357-1366.
|
||
Epub 2018 Feb 21
|
||
doi: 10.1016/S0140-6736(17)32802-7.
|
||
<span class="bold">PMID: </span><a href="/pubmed/29477251" target="_blank">29477251</a><a href="/pmc/articles/PMC5889788" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(%22amitriptyline%22%5Btiab%3A~0%5D)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">See all (492)</a></div></div>
|
||
</div>
|
||
<div class="display-none help-popup" id="guidelinesHelpPM">These guidelines are articles in PubMed that match specific search criteria developed by MedGen to capture the most relevant practice guidelines. This list may not be comprehensive and may include broader topics as well. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div><div class="display-none help-popup" id="guidelinesHelpCurated">These guidelines are manually curated by the MedGen team
|
||
to supplement articles available in PubMed. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div>
|
||
<div class="portlet mgSection" id="ID_114">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Suggested_Reading">Suggested Reading</h1><a sid="114" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><h3 class="subhead">PubMed</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/27997040">Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Hicks JK,
|
||
Sangkuhl K,
|
||
Swen JJ,
|
||
Ellingrod VL,
|
||
Müller DJ,
|
||
Shimoda K,
|
||
Bishop JR,
|
||
Kharasch ED,
|
||
Skaar TC,
|
||
Gaedigk A,
|
||
Dunnenberger HM,
|
||
Klein TE,
|
||
Caudle KE,
|
||
Stingl JC</span><br />
|
||
<span class="medgenPMjournal">Clin Pharmacol Ther</span>
|
||
2017 Jul;102(1):37-44.
|
||
Epub 2017 Feb 13
|
||
doi: 10.1002/cpt.597.
|
||
<span class="bold">PMID: </span><a href="/pubmed/27997040" target="_blank">27997040</a><a href="/pmc/articles/PMC5478479" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=" title="PubMed search"></a></div></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_103">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Recent_clinical_studies">Recent clinical studies</h1><a sid="103" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><h3 class="subhead">Etiology</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/1595364">Treatment resistance of depression after head injury: a preliminary study of amitriptyline response.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Dinan TG,
|
||
Mobayed M</span><br />
|
||
<span class="medgenPMjournal">Acta Psychiatr Scand</span>
|
||
1992 Apr;85(4):292-4.
|
||
doi: 10.1111/j.1600-0447.1992.tb01472.x.
|
||
<span class="bold">PMID: </span><a href="/pubmed/1595364" target="_blank">1595364</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/2527888">Ethological predictors of amitriptyline response in depressed outpatients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Troisi A,
|
||
Pasini A,
|
||
Bersani G,
|
||
Grispini A,
|
||
Ciani N</span><br />
|
||
<span class="medgenPMjournal">J Affect Disord</span>
|
||
1989 Sep-Oct;17(2):129-36.
|
||
doi: 10.1016/0165-0327(89)90035-9.
|
||
<span class="bold">PMID: </span><a href="/pubmed/2527888" target="_blank">2527888</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Amitriptyline%20response%22%20AND%20Etiology%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (2)</a></div><h3 class="subhead">Diagnosis</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/2527888">Ethological predictors of amitriptyline response in depressed outpatients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Troisi A,
|
||
Pasini A,
|
||
Bersani G,
|
||
Grispini A,
|
||
Ciani N</span><br />
|
||
<span class="medgenPMjournal">J Affect Disord</span>
|
||
1989 Sep-Oct;17(2):129-36.
|
||
doi: 10.1016/0165-0327(89)90035-9.
|
||
<span class="bold">PMID: </span><a href="/pubmed/2527888" target="_blank">2527888</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/3104447">Prediction of the amitriptyline response: psychopathology versus neuroendocrinology.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Sauer H,
|
||
Kick H,
|
||
Minne HW,
|
||
Schneider B</span><br />
|
||
<span class="medgenPMjournal">Int Clin Psychopharmacol</span>
|
||
1986 Oct;1(4):284-95.
|
||
doi: 10.1097/00004850-198610000-00002.
|
||
<span class="bold">PMID: </span><a href="/pubmed/3104447" target="_blank">3104447</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/7115012">Hypothalamic-pituitary-adrenal axis activity and tricyclic response in major depression.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Nelson WH,
|
||
Orr WW Jr,
|
||
Stevenson JM,
|
||
Shane SR</span><br />
|
||
<span class="medgenPMjournal">Arch Gen Psychiatry</span>
|
||
1982 Sep;39(9):1033-6.
|
||
doi: 10.1001/archpsyc.1982.04290090031007.
|
||
<span class="bold">PMID: </span><a href="/pubmed/7115012" target="_blank">7115012</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Amitriptyline%20response%22%20AND%20Diagnosis%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (3)</a></div><h3 class="subhead">Therapy</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/8352668">Propranolol and amitriptyline in prophylaxis of migraine. Pharmacokinetic and therapeutic effects.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Ziegler DK,
|
||
Hurwitz A,
|
||
Preskorn S,
|
||
Hassanein R,
|
||
Seim J</span><br />
|
||
<span class="medgenPMjournal">Arch Neurol</span>
|
||
1993 Aug;50(8):825-30.
|
||
doi: 10.1001/archneur.1993.00540080036010.
|
||
<span class="bold">PMID: </span><a href="/pubmed/8352668" target="_blank">8352668</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/1595364">Treatment resistance of depression after head injury: a preliminary study of amitriptyline response.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Dinan TG,
|
||
Mobayed M</span><br />
|
||
<span class="medgenPMjournal">Acta Psychiatr Scand</span>
|
||
1992 Apr;85(4):292-4.
|
||
doi: 10.1111/j.1600-0447.1992.tb01472.x.
|
||
<span class="bold">PMID: </span><a href="/pubmed/1595364" target="_blank">1595364</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/2527888">Ethological predictors of amitriptyline response in depressed outpatients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Troisi A,
|
||
Pasini A,
|
||
Bersani G,
|
||
Grispini A,
|
||
Ciani N</span><br />
|
||
<span class="medgenPMjournal">J Affect Disord</span>
|
||
1989 Sep-Oct;17(2):129-36.
|
||
doi: 10.1016/0165-0327(89)90035-9.
|
||
<span class="bold">PMID: </span><a href="/pubmed/2527888" target="_blank">2527888</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/7446778">Behavioral predictors of amitriptyline response in depression.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Ranelli CJ,
|
||
Miller RE</span><br />
|
||
<span class="medgenPMjournal">Am J Psychiatry</span>
|
||
1981 Jan;138(1):30-4.
|
||
doi: 10.1176/ajp.138.1.30.
|
||
<span class="bold">PMID: </span><a href="/pubmed/7446778" target="_blank">7446778</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/4554191">Predictors of amitriptyline response in outpatient depressives.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Downing RW,
|
||
Rickels K</span><br />
|
||
<span class="medgenPMjournal">J Nerv Ment Dis</span>
|
||
1972 Apr;154(4):248-63.
|
||
doi: 10.1097/00005053-197204000-00003.
|
||
<span class="bold">PMID: </span><a href="/pubmed/4554191" target="_blank">4554191</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Amitriptyline%20response%22%20AND%20Therapy%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (7)</a></div><h3 class="subhead">Prognosis</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/8352668">Propranolol and amitriptyline in prophylaxis of migraine. Pharmacokinetic and therapeutic effects.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Ziegler DK,
|
||
Hurwitz A,
|
||
Preskorn S,
|
||
Hassanein R,
|
||
Seim J</span><br />
|
||
<span class="medgenPMjournal">Arch Neurol</span>
|
||
1993 Aug;50(8):825-30.
|
||
doi: 10.1001/archneur.1993.00540080036010.
|
||
<span class="bold">PMID: </span><a href="/pubmed/8352668" target="_blank">8352668</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/2527888">Ethological predictors of amitriptyline response in depressed outpatients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Troisi A,
|
||
Pasini A,
|
||
Bersani G,
|
||
Grispini A,
|
||
Ciani N</span><br />
|
||
<span class="medgenPMjournal">J Affect Disord</span>
|
||
1989 Sep-Oct;17(2):129-36.
|
||
doi: 10.1016/0165-0327(89)90035-9.
|
||
<span class="bold">PMID: </span><a href="/pubmed/2527888" target="_blank">2527888</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/3104447">Prediction of the amitriptyline response: psychopathology versus neuroendocrinology.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Sauer H,
|
||
Kick H,
|
||
Minne HW,
|
||
Schneider B</span><br />
|
||
<span class="medgenPMjournal">Int Clin Psychopharmacol</span>
|
||
1986 Oct;1(4):284-95.
|
||
doi: 10.1097/00004850-198610000-00002.
|
||
<span class="bold">PMID: </span><a href="/pubmed/3104447" target="_blank">3104447</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/7446778">Behavioral predictors of amitriptyline response in depression.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Ranelli CJ,
|
||
Miller RE</span><br />
|
||
<span class="medgenPMjournal">Am J Psychiatry</span>
|
||
1981 Jan;138(1):30-4.
|
||
doi: 10.1176/ajp.138.1.30.
|
||
<span class="bold">PMID: </span><a href="/pubmed/7446778" target="_blank">7446778</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/4554191">Predictors of amitriptyline response in outpatient depressives.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Downing RW,
|
||
Rickels K</span><br />
|
||
<span class="medgenPMjournal">J Nerv Ment Dis</span>
|
||
1972 Apr;154(4):248-63.
|
||
doi: 10.1097/00005053-197204000-00003.
|
||
<span class="bold">PMID: </span><a href="/pubmed/4554191" target="_blank">4554191</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Amitriptyline%20response%22%20AND%20Prognosis%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (5)</a></div><h3 class="subhead">Clinical prediction guides</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/8352668">Propranolol and amitriptyline in prophylaxis of migraine. Pharmacokinetic and therapeutic effects.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Ziegler DK,
|
||
Hurwitz A,
|
||
Preskorn S,
|
||
Hassanein R,
|
||
Seim J</span><br />
|
||
<span class="medgenPMjournal">Arch Neurol</span>
|
||
1993 Aug;50(8):825-30.
|
||
doi: 10.1001/archneur.1993.00540080036010.
|
||
<span class="bold">PMID: </span><a href="/pubmed/8352668" target="_blank">8352668</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/2527888">Ethological predictors of amitriptyline response in depressed outpatients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Troisi A,
|
||
Pasini A,
|
||
Bersani G,
|
||
Grispini A,
|
||
Ciani N</span><br />
|
||
<span class="medgenPMjournal">J Affect Disord</span>
|
||
1989 Sep-Oct;17(2):129-36.
|
||
doi: 10.1016/0165-0327(89)90035-9.
|
||
<span class="bold">PMID: </span><a href="/pubmed/2527888" target="_blank">2527888</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/3104447">Prediction of the amitriptyline response: psychopathology versus neuroendocrinology.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Sauer H,
|
||
Kick H,
|
||
Minne HW,
|
||
Schneider B</span><br />
|
||
<span class="medgenPMjournal">Int Clin Psychopharmacol</span>
|
||
1986 Oct;1(4):284-95.
|
||
doi: 10.1097/00004850-198610000-00002.
|
||
<span class="bold">PMID: </span><a href="/pubmed/3104447" target="_blank">3104447</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/7446778">Behavioral predictors of amitriptyline response in depression.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Ranelli CJ,
|
||
Miller RE</span><br />
|
||
<span class="medgenPMjournal">Am J Psychiatry</span>
|
||
1981 Jan;138(1):30-4.
|
||
doi: 10.1176/ajp.138.1.30.
|
||
<span class="bold">PMID: </span><a href="/pubmed/7446778" target="_blank">7446778</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/4554191">Predictors of amitriptyline response in outpatient depressives.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Downing RW,
|
||
Rickels K</span><br />
|
||
<span class="medgenPMjournal">J Nerv Ment Dis</span>
|
||
1972 Apr;154(4):248-63.
|
||
doi: 10.1097/00005053-197204000-00003.
|
||
<span class="bold">PMID: </span><a href="/pubmed/4554191" target="_blank">4554191</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Amitriptyline%20response%22%20AND%20Clinical%20prediction%20guides%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (5)</a></div></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_120">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Therapeutic_recommendations">Therapeutic recommendations</h1><a sid="120" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln" id="therapeutic"><strong>From <a href="https://www.ncbi.nlm.nih.gov/books/NBK425165" target="_blank">Medical Genetics Summaries</a></strong><br /><div id="TheraputicContent"><div class="divPopper rprt" id="amitriptyline_REF_1" style="display: none;">1. AMITRIPTYLINE HYDROCHLORIDE- amitriptyline hydrochloride tablet, film coated. Durham, NC: Inc, A.H.; 2016. Available from: <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6d2c80-fbc8-444e-bdd3-6a91fe1b95bd" target="_blank">https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6d2c80-fbc8-444e-bdd3-6a91fe1b95bd</a>.</div><div class="divPopper rprt" id="amitriptyline_REF_2" style="display: none;">2. Kevin Hicks J., Sangkuhl K., Swen J.J., Ellingrod V.L., et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC(R)) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update. Clin Pharmacol Ther. 2016.</div><div class="divPopper rprt" id="amitriptyline_REF_32" style="display: none;">32. Royal Dutch Pharmacists Association (KNMP). Dutch Pharmacogenetics Working Group (DPWG). Pharmacogenetic Guidelines [Internet]. Netherlands. Amitriptyline – CYP2D6 [Cited March 2017]. Available from: <a href="http://kennisbank.knmp.nl" target="_blank">http://kennisbank.knmp.nl</a> [Access is restricted to KNMP membership.]</div><p><b>This section contains excerpted</b>
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<sup>1</sup>
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||
<b>information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.</b>
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</p><p><b>2016 Statement from the US Food and Drug Administration (FDA):</b>
|
||
The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).</p><p>In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).</p><p>Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6.</p><p><b>Please review the complete therapeutic recommendations that are located here:</b>
|
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(<a title="click for more information" class="jig-ncbipopper s_TOP" href="#amitriptyline_REF_1" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">1</a>).</p><p><b>2016 Statement from the Clinical Pharmacogenetics Implementation Consortium (CPIC):</b>
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</p><p><i>CYP2D6 dosing recommendations.</i></p><p>[…]. The recommended starting dose of amitriptyline or nortriptyline does not need adjustment for those with genotypes predictive of CYP2D6 normal metabolism. A 25% reduction of the recommended dose may be considered for CYP2D6 intermediate metabolizers. The strength of this recommendation is classified as “moderate” because patients with a CYP2D6 activity score of 1.0 are inconsistently categorized as intermediate or normal metabolizers in the literature, making these studies difficult to evaluate.</p><p>CYP2D6 ultrarapid metabolizers have a higher probability of failing amitriptyline or nortriptyline pharmacotherapy due to subtherapeutic plasma concentrations, and alternate agents are preferred. There are documented cases of CYP2D6 ultrarapid metabolizers receiving large doses of nortriptyline in order to achieve therapeutic concentrations. However, very high plasma concentrations of the nortriptyline hydroxy-metabolite were present, which may increase the risk for cardiotoxicity. If a tricyclic is warranted, there are insufficient data in the literature to calculate a starting dose for a patient with CYP2D6 ultrarapid metabolizer status, and therapeutic drug monitoring is strongly recommended. Adverse effects are more likely in CYP2D6 poor metabolizers due to elevated tricyclic plasma concentrations; therefore, alternate agents are preferred. If a tricyclic is warranted, consider a 50% reduction of the usual dose, and therapeutic drug monitoring is strongly recommended.</p><p><i>CYP2C19 dosing recommendations.</i></p><p>[…]. The usual starting dose of amitriptyline may be used in CYP2C19 normal and intermediate metabolizers. Although CYP2C19 intermediate metabolizers would be expected to have a modest increase in the ratio of amitriptyline to nortriptyline plasma concentrations, the evidence does not indicate that CYP2C19 intermediate metabolizers should receive an alternate dose.</p><p>Patients taking amitriptyline who are CYP2C19 rapid or ultrarapid metabolizers may be at risk for having low plasma concentrations and an imbalance between parent drug and metabolites causing treatment failure and/or adverse events. Although the CYP2C19*17 allele did not alter the sum of amitriptyline plus nortriptyline plasma concentrations, it was associated with higher nortriptyline plasma concentrations, possibly increasing the risk of adverse events. For patients taking amitriptyline, extrapolated pharmacokinetic data suggest that CYP2C19 rapid or ultrarapid metabolizers may need a dose increase. Due to the need for further studies investigating the clinical importance of CYP2C19*17 regarding tricyclic metabolism and the possibility of altered concentrations, we recommend to consider an alternative tricyclic or other drug not affected by CYP2C19. This recommendation is classified as optional due to limited available data. If amitriptyline is administered to a CYP2C19 rapid or ultrarapid metabolizer, therapeutic drug monitoring is recommended.</p><p>CYP2C19 poor metabolizers are expected to have a greater ratio of amitriptyline to nortriptyline plasma concentrations. The elevated amitriptyline plasma concentrations may increase the chance of a patient experiencing side effects. Use an alternative agent not metabolized by CYP2C19 (e.g., nortriptyline and desipramine) or consider a 50% reduction of the usual amitriptyline starting dose along with therapeutic drug monitoring.</p><p><b>Please review the complete therapeutic recommendations that are located here:</b>
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(<a title="click for more information" class="jig-ncbipopper s_TOP" href="#amitriptyline_REF_2" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">2</a>).</p><p><b>2011 Summary of recommendations from the Pharmacogenetics Working Group of the Royal Dutch Association for the Advancement of Pharmacy (KNMP)</b>
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</p><p><b>For CYP2D6 ultrarapid metabolizers:</b>
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</p><p>The genetic polymorphism leads to increased metabolic capacity of CYP2D6, which may cause a decrease in the plasma concentrations of amitriptyline and its active metabolite nortriptyline and increased plasma concentrations of the active metabolites E-10-OH-amitriptyline and E-10-OH- nortriptyline.</p><p>Recommendation:</p><ol><li>Choose an alternative if possible. Antidepressants that are not metabolized via CYP2D6 - or to a lesser extent - include, for example, citalopram and sertraline.</li><li>If an alternative is not an option: increase the dose to 1.25 times the standard dose, monitor the plasma concentrations and be alert to potential therapy failure due to decreased amitriptyline plus nortriptyline plasma concentrations and to increased plasma concentrations of the potentially cardiotoxic, active hydroxy metabolites.</li></ol><p><b>For CYP2D6 intermediate metabolizers:</b>
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</p><p>The genetic polymorphism leads to decreased metabolic capacity of CYP2D6, which may cause an increase in the plasma concentrations of amitriptyline and its active metabolite nortriptyline and decreased plasma concentrations of the active metabolites E-10-OH-amitriptyline and E-10-OH- nortriptyline.</p><p>Recommendation:</p><ol><li>Choose an alternative if possible. Antidepressants that are not metabolized via CYP2D6 - or to a lesser extent - include, for example, citalopram and sertraline.</li><li>If an alternative is not an option: use 60% of the standard dose and monitor the plasma concentrations of amitriptyline and nortriptyline</li></ol><p>As side effects are related to nortriptyline plasma concentrations and the efficacy to amitriptyline plus nortriptyline plasma concentrations, which are influenced to a lesser extent by CYP2D6, it is not known whether it is possible to reduce the dose to such an extent that the side effects disappear, but the efficacy is maintained.</p><p><b>For CYP2D6 poor metabolizers:</b>
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</p><p>The genetic polymorphism leads to decreased metabolic capacity of CYP2D6, which may cause an increase in the plasma concentrations of amitriptyline and its active metabolite nortriptyline and decreased plasma concentrations of the active metabolites E-10-OH-amitriptyline and E-10-OH- nortriptyline.</p><p>Recommendation:</p><ol><li>Choose an alternative if possible. Antidepressants that are not metabolized via CYP2D6 - or to a lesser extent - include, for example, citalopram and sertraline.</li><li>If an alternative is not an option: use 50% of the standard dose and monitor the plasma concentrations of amitriptyline and nortriptyline</li></ol><p>As side effects are related to nortriptyline plasma concentrations and the efficacy to amitriptyline plus nortriptyline plasma concentrations, which are influenced to a lesser extent by CYP2D6, it is not known whether it is possible to reduce the dose to such an extent that the side effects disappear, but the efficacy is maintained.</p><p><b>Please review the complete therapeutic recommendations that are located here:</b>
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(<a title="click for more information" class="jig-ncbipopper s_TOP" href="#amitriptyline_REF_32" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">32</a>).</p><p><sup>1</sup>
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The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug.</p></div></div>
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<h2 class="offscreen_noflow">Supplemental Content</h2>
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<div class="portlet_content ln"><ul><li><a href="/gtr/tests?term=CN176769%5bDISCUI%5d&filter=method%3A2%5F8" target="_blank">Deletion/duplication analysis (7)</a></li>
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<li><a href="/gtr/tests?term=CN176769%5bDISCUI%5d&filter=method%3A2%5F17" target="_blank">Mutation scanning of the entire coding region (1)</a></li>
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<div class="portlet_content ln"><ul class="a_poppers"><li><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(%22amitriptyline%22%5Btiab%3A~0%5D)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">PubMed</a><div class="help-popup">See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div></li></ul></div>
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<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
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