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

Kimberly Peterson, Eric Dieperink, Johanna Anderson, Erin Boundy, Lauren Ferguson, Mark Helfand

Research output: Contribution to journalReview article

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1649-1661
Number of pages13
JournalPsychopharmacology
Volume234
Issue number11
DOIs
StatePublished - Jun 1 2017

Fingerprint

Pharmacogenetics
Major Depressive Disorder
Antidepressive Agents
Cost-Benefit Analysis
Cytochrome P-450 CYP2D6
Comorbidity
Cytochrome P-450 CYP1A2
Therapeutics
MEDLINE
Registries
Cohort Studies
Research

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder. / Peterson, Kimberly; Dieperink, Eric; Anderson, Johanna; Boundy, Erin; Ferguson, Lauren; Helfand, Mark.

In: Psychopharmacology, Vol. 234, No. 11, 01.06.2017, p. 1649-1661.

Research output: Contribution to journalReview article

@article{198bd0f865a74718b20476b2c30f46a2,
title = "Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder",
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{\circledR}, 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.",
keywords = "Antidepressant treatment, Major depressive disorder, Pharmacogenomics, Systematic review",
author = "Kimberly Peterson and Eric Dieperink and Johanna Anderson and Erin Boundy and Lauren Ferguson and Mark Helfand",
year = "2017",
month = "6",
day = "1",
doi = "10.1007/s00213-017-4622-9",
language = "English (US)",
volume = "234",
pages = "1649--1661",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "11",

}

TY - JOUR

T1 - Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder

AU - Peterson, Kimberly

AU - Dieperink, Eric

AU - Anderson, Johanna

AU - Boundy, Erin

AU - Ferguson, Lauren

AU - Helfand, Mark

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - Antidepressant treatment

KW - Major depressive disorder

KW - Pharmacogenomics

KW - Systematic review

UR - http://www.scopus.com/inward/record.url?scp=85018251884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018251884&partnerID=8YFLogxK

U2 - 10.1007/s00213-017-4622-9

DO - 10.1007/s00213-017-4622-9

M3 - Review article

VL - 234

SP - 1649

EP - 1661

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 11

ER -