From pharmacogenetics to pharmacogenomics: the way toward the personalization of antidepressant treatment

Abstract

Objective: Major depressive disorder is the most common psychiatric disorder, worldwide, yet response and remission rates are still unsatisfactory. The identification of genetic predictors of antidepressant (AD) response could provide a promising opportunity to improve current AD efficacy through the personalization of treatment. The major steps and findings along this path are reviewed together with their clinical implications and limitations.

Method: We systematically reviewed the literature through MEDLINE and Embase database searches, using any word combination of "antidepressant," "gene," "polymorphism," "pharmacogenetics," "genome-wide association study," "GWAS," "response," and "adverse drug reactions." Experimental works and reviews published until March 2012 were collected and compared.

Results: Numerous genes pertaining to several functional systems were associated with AD response. The more robust findings were found for the following genes: solute carrier family 6 (neurotransmitter transporter), member 4; serotonin receptor 1A and 2A; brain-derived neurotrophic factor; and catechol-O-methyltransferase. Genome-wide association studies (GWASs) provided many top markers, even if none of them reached genome-wide significance.

Conclusions: AD pharmacogenetics have not produced any knowledge applicable to routine clinical practice yet, as results were mainly inconsistent across studies. Despite this, the rising awareness about methodological deficits of past studies could allow for the identication of more suitable strategies, such as the integration of the GWAS approach with the candidate gene approach, and innovative methodologies, such as pathway analysis and study of depressive endophenotypes.