, Volume 234, Issue 11, pp 1649–1661 | Cite as

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

  • Kimberly PetersonEmail author
  • Eric Dieperink
  • Johanna Anderson
  • Erin Boundy
  • Lauren Ferguson
  • Mark Helfand



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.


Pharmacogenomics 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.


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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2017

Authors and Affiliations

  • Kimberly Peterson
    • 1
    Email author
  • Eric Dieperink
    • 2
  • Johanna Anderson
    • 1
  • Erin Boundy
    • 1
  • Lauren Ferguson
    • 1
  • Mark Helfand
    • 1
  1. 1.Evidence-based Synthesis Program (ESP) Coordinating Center, VA Portland Health Care SystemDepartment of Veterans AffairsPortlandUSA
  2. 2.Mental/Behavioral Health, Minneapolis VA Health Care SystemDepartment of Veterans AffairsMinneapolisUSA

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