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Testing for Cytochrome P450 Polymorphisms in Adults With Non-Psychotic Depression Treated With Selective Serotonin Reuptake Inhibitors (SSRIs)
Evidence Reports/Technology Assessments, No. 146
Investigators: David B Matchar, MD, Principal Investigator, Mugdha E Thakur, MD, Co-Principal Investigator, Iris Grossman, PhD, Douglas C McCrory, MD, MHS, Lori A Orlando, MD, MHS, David C Steffens, MD, MHS, David B Goldstein, PhD, Kathryn E Cline, MHS, Project Manager, and Rebecca N Gray, DPhil, Editor.
Structured Abstract
Objectives:
To determine if testing for cytochrome P450 (CYP450) polymorphisms in adults entering selective serotonin reuptake inhibitor (SSRI) treatment for non-psychotic depression leads to improvement in outcomes, or if testing results are useful in medical, personal, or public health decisionmaking.
Data Sources:
We searched MEDLINE®, the Cochrane Database of Abstracts of Reviews of Effects, PsychInfo, HealthSTAR, and CINAHL, and reviewed the reference lists of included articles and relevant review articles and meta-analyses for eligible studies. We also included documents from the U.S. Food and Drug Administration (FDA) that could be publicly accessed.
Review Methods:
We developed an analytic framework and identified key questions to guide the review process. Project-specific inclusion/exclusion criteria were also developed and were used by paired researchers independently to review both abstracts and full-text articles; both researchers were required to agree on inclusion status at the full-text stage. Abstractors evaluated each included article for factors affecting internal and external validity.
Results:
A review of 1,200 abstracts led to the final inclusion of 37 articles. The evidence indicates the existence of tests with high sensitivity and specificity for detecting only a few of the more common known polymorphisms of 2D6, 2C19, 2C8, 2C9, and 1A1. There is mixed evidence regarding the association between CYP450 genotypes and SSRI metabolism, efficacy, and tolerability in the treatment of depression, mainly from a series of heterogeneous studies in small samples. There are no data regarding: (a) if testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes versus not testing, or if testing results are useful in medical, personal, or public health decisionmaking; (b) if CYP450 testing influences depression management decisions by patients and providers in ways that could improve or worsen outcomes; or (c) if there are direct or indirect harms associated with testing for CYP450 polymorphisms or with subsequent management options.
Conclusions:
There is a paucity of good-quality data addressing the questions of whether testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes, or whether testing results are useful in medical, personal, or public health decisionmaking.
Contents
- Preface
- Acknowledgments
- Executive Summary
- 1. Introduction
- 2. Methods
- 3. Results
- Question 1: Overarching Question
- Question 2: Analytic Validity of Tests That Identify Key CYP450 Polymorphisms
- Question 3a: CYP450 Genotypes and Metabolism of SSRIs
- Question 3b: CYP450 Testing and Efficacy of SSRIs
- Question 3c: CYP450 Testing and Adverse Drug Reactions
- Question 4: Management Decisions, Clinical Outcomes, and Decisionmaking
- Question 5: Harms Associated With CYP450 Testing and Subsequent Management Options
- Model of Treatment for Major Depression
- 4. Discussion
- 5. Future Research
- 6. Conclusions
- List of Acronyms/Abbreviations
- Appendixes
- References Cited in the Evidence Report
- Listing of Included Studies (alphabetical)
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-02-0025. Prepared by: Duke Evidence-based Practice Center, Durham, NC.
Suggested citation:
Matchar DB, Thakur ME, Grossman I, McCrory DC, Orlando LA, Steffens DC, Goldstein DB, Cline KE, Gray RN. Testing for Cytochrome P450 Polymorphisms in Adults With Non-Psychotic Depression Treated With Selective Serotonin Reuptake Inhibitors (SSRIs). Evidence Report/Technology Assessment No. 146. (Prepared by the Duke Evidence-based Practice Center under Contract No. 290-02-0025.) AHRQ Publication No. 07-E002. Rockville, MD: Agency for Healthcare Research and Quality. January 2007.
This report is based on research conducted by the Duke Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0025). The findings and conclusions in this document are those of the author(s), who are responsible for its contents, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.
This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
None of the investigators has any affiliations or financial involvement that conflicts with the material presented in this report.
- 1
540 Gaither Road, Rockville, MD 20850. www
.ahrq.gov
- Review Review of evidence for genetic testing for CYP450 polymorphisms in management of patients with nonpsychotic depression with selective serotonin reuptake inhibitors.[Genet Med. 2007]Review Review of evidence for genetic testing for CYP450 polymorphisms in management of patients with nonpsychotic depression with selective serotonin reuptake inhibitors.Thakur M, Grossman I, McCrory DC, Orlando LA, Steffens DC, Cline KE, Gray RN, Farmer J, DeJesus G, O'Brien C, et al. Genet Med. 2007 Dec; 9(12):826-35.
- Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors.[Genet Med. 2007]Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors.Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Genet Med. 2007 Dec; 9(12):819-25.
- Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine.[Basic Clin Pharmacol Toxicol. ...]Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine.Scordo MG, Spina E, Dahl ML, Gatti G, Perucca E. Basic Clin Pharmacol Toxicol. 2005 Nov; 97(5):296-301.
- CYP450 genotype and aggressive behavior on selective serotonin reuptake inhibitors.[Pharmacogenomics. 2017]CYP450 genotype and aggressive behavior on selective serotonin reuptake inhibitors.Ekhart C, Matic M, Kant A, van Puijenbroek E, Schaik RV. Pharmacogenomics. 2017 May; 18(7):613-620. Epub 2017 May 4.
- Review [Use of antidepressant drugs in schizophrenic patients with depression].[Encephale. 2006]Review [Use of antidepressant drugs in schizophrenic patients with depression].Micallef J, Fakra E, Blin O. Encephale. 2006 Mar-Apr; 32(2 Pt 1):263-9.
- Testing for Cytochrome P450 Polymorphisms in Adults With Non-Psychotic Depressio...Testing for Cytochrome P450 Polymorphisms in Adults With Non-Psychotic Depression Treated With Selective Serotonin Reuptake Inhibitors (SSRIs)
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