Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder
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This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder.
We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358).
We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities. CNSDose (ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1) is the only pharmacogenomics test that significantly improved remission (one additional remitting patient in 12 weeks per three genotyped, 95% CI 1.7 to 3.5) and reduced intolerability in an RCT. ABCB1 genotyping leads to one additional remitting patient in 5 weeks per three genotyped (95% CI 3 to 20), but tolerability was not reported. In an RCT, GeneSight (CYP2D6, CYPC19, CYP1A2, SLC6A4, HTR2A) did not statistically significantly improve remission, and evidence is inconclusive about its tolerability. Evidence is generally low strength because RCTs were few and underpowered. Cost-effectiveness is unclear due to lack of directly observed cost-effectiveness outcomes. We found no studies that evaluated whether pharmacogenomics shortens time to optimal treatment, whether improvements were due to switches to genetically congruent medication, or whether effectiveness varies based on test and patient characteristics.
Certain pharmacogenomics tools show promise of improving short-term remission rates in women in their mid-40s with few comorbidities. But, important evidence limitations preclude recommending their widespread use and indicate a need for further research.
KeywordsPharmacogenomics Major depressive disorder Systematic review Antidepressant treatment
We would like to thank Julia Haskin, MA, for editorial support. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative (QUERI), Evidence-Based Synthesis Program (ESP).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Agency for Healthcare Research and Quality (2014) Methods guide for effectiveness and comparative effectiveness reviews. AHRQ Publication No. 10(14)-EHC063-EF, RockvilleGoogle Scholar
- American Psychiatric Association (2010) Practice guideline for the treatment of patients with major depressive disorder. Am Psychiatric AssocGoogle Scholar
- Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Möller H-J (2013) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry 14:334–385CrossRefPubMedGoogle Scholar
- Bauer M, Whybrow PC, Angst J, Versiani M, Möller H-J (2015) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 2: maintenance treatment of major depressive disorder - update 2015. World J Biol Psychiatry 16:76–95CrossRefPubMedGoogle Scholar
- Berkman ND, Lohr KN, Ansari M et al. (2013) Grading the strength of a body of evidence when assessing health care interventions for the effective health care program of the agency for healthcare research and quality: an update methods guide for effectiveness and comparative effectiveness reviewsGoogle Scholar
- Bousman CA, Hopwood M (2016) Commercial pharmacogenetic-based decision-support tools in psychiatry. The Lancet PsychiatryGoogle Scholar
- Brennan FX, Gardner KR, Lombard J et al. (2015) A naturalistic study of the effectiveness of pharmacogenetic testing to guide treatment in psychiatric patients with mood and anxiety disorders. The primary care companion for CNS disorders 17Google Scholar
- Centers for Disease Control and Prevention, National Office of Public Health Genomics. 2007. ACCE model process for evaluating genetic tests [online]. Available: http://www.cdc.gov/genomics/gtesting/ACCE/index.htm [Accessed March 2016]
- Department of Veterans Affairs: The Management of MDD Working Group (2016) VA/DoD clinical practice guideline for the management of major depressive disorderGoogle Scholar
- ECRI Institute (2015a) GeneSight psychotropic pharmacogenomic testing (Assurex Health, Inc.) for guiding medication selection for patients with neuropsychiatric disorders. Genetic Test Product Brief Google Scholar
- ECRI Institute (2015b) Pharmacogenetic testing to guide treatment of behavioral and mental health disorders. Genetic Test Hotline Response Google Scholar
- Effective Practice and Organization of Care (2013) What study designs should be included in an EPOC review? EPOC Resources for review authorsGoogle Scholar
- Elliott LS, Henderson JC, Neradilek MB, Moyer NA, Ashcraft KC, Thirumaran RK (2017) Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: a prospective pilot randomized controlled trial. PLoS One 12:e0170905CrossRefPubMedPubMedCentralGoogle Scholar
- Fu R, Gartlehner G, Grant M et al. (2010) Chapter 12. Conducting quantitative synthesis when comparing medical interventions. Methods guide for effectiveness and comparative effectiveness reviews. Agency for Healthcare Research and QualityGoogle Scholar
- Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, Drews MS, Eisterhold LL, Geske J, Mrazek DA (2013) Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics 23:535–548CrossRefPubMedGoogle Scholar
- Higgins J, Green S (2011) Cochrane handbook for systematic reviews of interventions. Version 5.1.0.Google Scholar
- Howland RH (2014a) Pharmacogenetic testing in psychiatry: not (quite) ready for primetime. J Psychosoc Nurs Ment Health Serv 52:13–16Google Scholar
- Howland RH (2014b) Pharmacogenetic testing in psychiatry: not (quite) ready for primetime. J Psychosoc Nurs Ment Health Serv 52:13–16Google Scholar
- Matchar DB, Thakur ME, Grossman I et al. (2007) Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs)Google Scholar
- McDonagh M, Peterson K, Raina P et al. (2014) Methods guide for effectiveness and comparative effectiveness reviews: chapter 7: avoiding bias in selecting studies. Agency for Healthcare Research and QualityGoogle Scholar
- National Institute for Health and Care Excellence (2009) Depression in adults: recognition and managementGoogle Scholar
- Norris S, Atkins D, Bruening W et al. (2010) Chapter 8. Selecting observational studies for comparing medical interventions. Methods guide for effectiveness and comparative effectiveness reviews. Agency for Healthcare Research and QualityGoogle Scholar
- Peterson K, Dieperink E, Ferguson L et al. (2016) Evidence brief: the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomic testing guided versus unguided antidepressant treatment for major depressive disorderGoogle Scholar
- Pyne, J (2009) Genetic testing decision analysis model for antidepressant treatmentGoogle Scholar
- Rosenblat, JD, Lee, Y, McIntyre, RS (2017) Does pharmacogenomic testing improve clinical outcomes for major depressive disorder? A systematic review of clinical trials and cost-effectiveness studies. J Clin PsychiatryGoogle Scholar
- Squassina A, Manchia M, Manolopoulos VG, Artac M, Lappa-Manakou C, Karkabouna S, Mitropoulos K, Zompo MD, Patrinos GP (2010) Realities and expectations of pharmacogenomics and personalized medicine: impact of translating genetic knowledge into clinical practice. Pharmacogenomics 11:1149–1167CrossRefPubMedGoogle Scholar
- Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR* D: implications for clinical practice. Am J Psychiatr 163:28–40CrossRefPubMedGoogle Scholar
- Viswanathan, M, Ansari, M, Berkman, ND et al. (2012) Assessing the risk of bias of individual studies in systematic reviews of health care interventions:methods guide for comparative effectiveness reviews, Rockville, MDGoogle Scholar
- Winner, JG, Carhart, JM, Altar, CA et al. (2015) Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a 1 year prospective evaluation. Current medical research and opinionGoogle Scholar