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

Psychopharmacology volume 234, pages 1649–1661 (2017)Cite this article

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.

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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).

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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

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  1. Kimberly Peterson
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Correspondence to Kimberly Peterson.

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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

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Keywords

  • Pharmacogenomics
  • Major depressive disorder
  • Systematic review
  • Antidepressant treatment