Skip to main content

Advertisement

SpringerLink
Log in

Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Objective

This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder.

Methods

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).

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Agency for Healthcare Research and Quality (2014) Methods guide for effectiveness and comparative effectiveness reviews. AHRQ Publication No. 10(14)-EHC063-EF, Rockville

    Google Scholar 

  • Alagoz O, Durham D, Kasirajan K (2016) Cost-effectiveness of one-time genetic testing to minimize lifetime adverse drug reactions. Pharmacogenomics J 16:129–136

    Article  CAS  PubMed  Google Scholar 

  • Altar CA, Carhart J, Allen JD, Hall-Flavin D, Winner J, Dechairo B (2015) Clinical utility of combinatorial pharmacogenomics-guided antidepressant therapy: evidence from three clinical studies. Mol Neuropsychiatry 1:145–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • American Psychiatric Association (2010) Practice guideline for the treatment of patients with major depressive disorder. Am Psychiatric Assoc

  • 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 14:334–385

    Article  PubMed  Google 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 16:76–95

    Article  PubMed  Google 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 reviews

  • Berm EJ, Looff M, Wilffert B, Boersma C, Annemans L, Vegter S, Boven JF, Postma MJ (2016) Economic evaluations of pharmacogenetic and pharmacogenomic screening tests: a systematic review. Second update of the literature. PLoS One 11:e0146262

    Article  PubMed  PubMed Central  Google Scholar 

  • Bousman CA, Hopwood M (2016) Commercial pharmacogenetic-based decision-support tools in psychiatry. The Lancet Psychiatry

  • Breitenstein B, Scheuer S, Pfister H, Uhr M, Lucae S, Holsboer F, Ising M, Bruckl TM (2014) The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study. Cns Spectrums 19:165–175

    Article  PubMed  Google Scholar 

  • Breitenstein B, Scheuer S, Bruckl TM, Meyer J, Ising M, Uhr M, Holsboer F (2016) Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: results from a randomized clinical study. J Psychiatr Res 73:86–95

    Article  PubMed  Google 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 17

  • 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]

  • de Leon J (2016) Pharmacogenetic tests in psychiatry: from fear to failure to hype. J Clin Psychopharmacol 36:299–304

    Article  PubMed  Google Scholar 

  • Department of Veterans Affairs: The Management of MDD Working Group (2016) VA/DoD clinical practice guideline for the management of major depressive disorder

  • Drozda K, Müller DJ, Bishop JR (2014) Pharmacogenomic testing for neuropsychiatric drugs: current status of drug labeling, guidelines for using genetic information, and test options. Pharmacother: J Hum Pharmacol Drug Ther 34:166–184

    Article  CAS  Google Scholar 

  • ECRI Institute (2015a) GeneSight psychotropic pharmacogenomic testing (Assurex Health, Inc.) for guiding medication selection for patients with neuropsychiatric disorders. Genetic Test Product Brief

  • ECRI Institute (2015b) Pharmacogenetic testing to guide treatment of behavioral and mental health disorders. Genetic Test Hotline Response

  • Effective Practice and Organization of Care (2013) What study designs should be included in an EPOC review? EPOC Resources for review authors

  • 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:e0170905

    Article  PubMed  PubMed Central  Google Scholar 

  • Fagerness J, Fonseca E, Hess GP, Scott R, Gardner KR, Koffler M, Fava M, Perlis R, Brennan FX, Lombard J (2014) Pharmacogenetic-guided psychiatric intervention associated with increased adherence and cost savings. Am J Manag Care 20:e146–e156

    PubMed  Google 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 Quality

  • Hall-Flavin DK, Winner JG, Allen JD, Jordan JJ, Nesheim RS, Snyder KA, Drews MS, Eisterhold LL, Biernacka JM, Mrazek DA (2012) Using a pharmacogenomic algorithm to guide the treatment of depression. Transl Psychiatry 2:e172

    Article  CAS  PubMed  PubMed Central  Google 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 23:535–548

    Article  CAS  PubMed  Google Scholar 

  • Hamilton SP (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higgins J, Green S (2011) Cochrane handbook for systematic reviews of interventions. Version 5.1.0.

  • Hornberger J, Li Q, Quinn B (2015) Cost-effectiveness of combinatorial pharmacogenomic testing for treatment-resistant major depressive disorder patients. Am J Manag Care 21:e357–e365

    PubMed  Google Scholar 

  • Howland RH (2014a) Pharmacogenetic testing in psychiatry: not (quite) ready for primetime. J Psychosoc Nurs Ment Health Serv 52:13–16

    Google Scholar 

  • Howland RH (2014b) Pharmacogenetic testing in psychiatry: not (quite) ready for primetime. J Psychosoc Nurs Ment Health Serv 52:13–16

    Google Scholar 

  • Jonas DE, Wilt TJ, Taylor BC, Wilkins TM, Matchar DB (2012) Challenges in and principles for conducting systematic reviews of genetic tests used as predictive indicators. J Gen Intern Med 27:83–93

    Article  PubMed Central  Google Scholar 

  • Marseille E, Larson B, Kazi DS, Kahn JG, Rosen S (2015) Thresholds for the cost–effectiveness of interventions: alternative approaches. Bull World Health Organ 93:118–124

    Article  PubMed  Google 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)

  • McDonagh M, Jonas D, Gartlehner G, Little A, Peterson K, Carson S, Gibson M, Helfand M (2012) Methods for the drug effectiveness review project. BMC Med Res Methodol 12:1

    Article  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 Quality

  • Müller DJ, Kekin I, Kao AC, Brandl EJ (2013) Towards the implementation of CYP2D6 and CYP2C19 genotypes in clinical practice: update and report from a pharmacogenetic service clinic. Int Rev Psychiatry 25:554–571

    Article  PubMed  Google Scholar 

  • National Institute for Health and Care Excellence (2009) Depression in adults: recognition and management

  • 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 Quality

  • Olgiati P, Bajo E, Bigelli M, De Ronchi D, Serretti A (2012) Should pharmacogenetics be incorporated in major depression treatment? Economic evaluation in high- and middle-income European countries. Prog Neuro-Psychopharmacol Biol Psychiatry 36:147–154

    Article  Google Scholar 

  • Perlis RH, Patrick A, Smoller JW, Wang PS (2009) When is pharmacogenetic testing for antidepressant response ready for the clinic? A cost-effectiveness analysis based on data from the STAR D study. Neuropsychopharmacology 34:2227–2236

    Article  CAS  PubMed  PubMed Central  Google 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 disorder

  • Prainsack B, Wolinsky H (2010) Direct-to-consumer genome testing: opportunities for pharmacogenomics research? Pharmacogenomics 11:651–655

    Article  PubMed  Google Scholar 

  • Pyne, J (2009) Genetic testing decision analysis model for antidepressant treatment

  • 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 Psychiatry

  • Rost K, Nutting P, Smith JL, Elliott CE, Dickinson M (2002) Managing depression as a chronic disease: a randomised trial of ongoing treatment in primary care. BMJ 325:934

    Article  PubMed  PubMed Central  Google Scholar 

  • Rush AJ, Trivedi M, Carmody TJ, Biggs MM, Shores-Wilson K, Ibrahim H, Crismon ML (2004) One-year clinical outcomes of depressed public sector outpatients: a benchmark for subsequent studies. Biol Psychiatry 56:46–53

    Article  PubMed  Google Scholar 

  • Serretti A, Olgiati P, Bajo E, Bigelli M, De Ronchi D (2011) A model to incorporate genetic testing (5-HTTLPR) in pharmacological treatment of major depressive disorders. World J Biol Psychiatry 12:501–515

    Article  PubMed  Google Scholar 

  • Singh AB (2015) Improved antidepressant remission in major depression via a pharmacokinetic pathway polygene pharmacogenetic report. Clin Psychopharmacol Neurosci 13:150–156

    Article  PubMed  PubMed Central  Google Scholar 

  • Singh AB, Bousman CA, Ng C, Berk M (2014) Antidepressant pharmacogenetics. Curr Opin Psychiatry 27:43–51

    Article  PubMed  Google 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 11:1149–1167

    Article  PubMed  Google Scholar 

  • Tansey KE, Guipponi M, Hu X, Domenici E, Lewis G, Malafosse A, Wendland JR, Lewis CM, McGuffin P, Uher R (2013) Contribution of common genetic variants to antidepressant response. Biol Psychiatry 73:679–682

    Article  CAS  PubMed  Google 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 163:28–40

    Article  PubMed  Google Scholar 

  • Ubel PA, Hirth RA, Chernew ME, Fendrick AM (2003) What is the price of life and why doesn’t it increase at the rate of inflation? Arch Intern Med 163:1637–1641

    Article  PubMed  Google 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, MD

  • Winner JG, Carhart JM, Altar CA, Allen JD, Dechairo BM (2013) A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med 16:219–227

    PubMed  Google 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 opinion

Download references

Acknowledgements

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).

Author information

Authors and Affiliations

  1. Evidence-based Synthesis Program (ESP) Coordinating Center, VA Portland Health Care System, Department of Veterans Affairs, 3710 SW U.S. Veterans Hospital Road, Mail Code: R&D 71, Portland, OR, 97239, USA

    Kimberly Peterson, Johanna Anderson, Erin Boundy, Lauren Ferguson & Mark Helfand

  2. Mental/Behavioral Health, Minneapolis VA Health Care System, Department of Veterans Affairs, Minneapolis, MN, USA

    Eric Dieperink

Authors
  1. Kimberly Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Dieperink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Johanna Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erin Boundy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lauren Ferguson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark Helfand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kimberly Peterson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peterson, K., Dieperink, E., Anderson, J. et al. Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder. Psychopharmacology 234, 1649–1661 (2017). https://doi.org/10.1007/s00213-017-4622-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4622-9

Keywords

Search

Navigation