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Review
. 2016 Jun;17(9):1029-40.
doi: 10.2217/pgs-2016-0024. Epub 2016 Jun 1.

Identifying genetic loci affecting antidepressant drug response in depression using drug-gene interaction models

Raymond Noordam  1   2 , Christy L Avery  3 , Loes E Visser  2   4 , Bruno H Stricker  2   5
Affiliations
Review

Identifying genetic loci affecting antidepressant drug response in depression using drug-gene interaction models

Raymond Noordam et al. Pharmacogenomics. 2016 Jun.

Abstract

Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., 'treated-only design', statistical power) and we will discuss how specifically drug-gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression.

Keywords: antidepressive agents; drug–gene interaction models; pharmacogenomics.

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Conflict of interest statement

Financial & competing interests disclosure CL Avery and BH Stricker acknowledges funding from R01HL103612 (NIH). CL Avery also acknowledges funding from 15GPSPG239 (American Heart Association). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript

Figures

<b>Figure 1.</b>
Figure 1.. Hypothetical randomized clinical trial on antidepressant response.
The dark gray area reflects the difference in response between depressive patients treated with antidepressant drugs depressive patients treated with placebo.
<b>Figure 2.</b>
Figure 2.. Hypothetical drug–gene interaction situations in a randomized clinical trial on antidepressant drug response in depression.
The trajectory of the depressive symptoms over time is depicted in antidepressant-treated patients as a solid line, and in placebo-treated patients as a dashed line. (A) Carriers of the variant allele (heterozygous and homozygous carriers combined for simplicity reasons) are associated with, on average, a larger decrease in depressive symptoms than homozygous carriers of the major allele, but the effect size is similar for users of antidepressant treatment and users of placebo treatment. (B) Carriers of the variant allele that use also antidepressant treatment have a steeper decline in depressive symptoms within the time period than homozygous carriers of the major allele and users of placebo treatment. This hypothetical genetic variant is therefore a modifier of antidepressant drug response.
<b>Figure 3.</b>
Figure 3.. Hypothetical drug–gene interaction situations in a (prospective) cohort study on antidepressant drug response in depression.
(A) No interaction and no association with cross-sectional assessments of depressive symptoms. (B) No interaction but association with cross-sectional assessments of depressive symptoms. (C) Interaction present, only association with cross-sectional assessments of depressive symptoms in treated participants.
See this image and copyright information in PMC

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