Application of Pharmacogenomics to Clinical Problems in Depression

Abstract

The goal of this article is to review the literature for evidence supporting an association between polymorphisms within drug target genes and clinical outcomes for treating depression, with a purpose to identify a research area having the most promising potential to be introduced into clinical settings, and thus, discussing the perspectives of genotyping in antidepressant therapy. A total of 67 articles were identified. Polymorphic sites within the serotonin transporter gene promoter, 5-HTTLPR, were the most studied polymorphisms. All except three articles were designed as cohort studies. The other three articles included two meta-analyses and one decision-analytic model. The main finding from these meta-analyses was that the l variant was associated with a better response to selective serotonin reuptake inhibitors. The main conclusion from the decision-analytic model study was that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment. Clinical outcomes of genotyping this polymorphism were evaluated by improvement of depression score, odds ratio and absolute risk reduction.

Anticipated Outcomes from Introduction of 5-HTTLPR Genotyping for Depressed Patients: An Expert Delphi Analysis

“…Two hundred and two coauthors were identified worldwide based on the review [17]. Available E-mail addresses were found for 131 authors.…”

“…All authors of articles on the topic of 5-HTTLPR genotyping identified in a performed review [17] were regarded as experts in this subject. These articles were 35 clinical studies, in which 5-HTTLPR genotyping was employed in clinical settings in order to explore the association between different genotypes and response to SSRIs and 4 relevant reviews regarding clinical application of 5-HTTLPR.…”

“…Based on the previously performed review, it was clear that pretreatment genotyping for 5-HTTLPR can have influence on reaching remission earlier; however, no studies directly comparing remission or response rates for testing and non-testing groups were identified [17]. Therefore, the first area of interest in this study was estimation of remission probabilities in case of introducing 5-HTTLPR genotyping as a pretreatment tool.…”

“…Therefore, the first area of interest in this study was estimation of remission probabilities in case of introducing 5-HTTLPR genotyping as a pretreatment tool. Another finding from the review [17,18,19] was that no data were reported regarding influence of 5-HTTLPR genotyping on preventing relapse; therefore, the second area of interest was to clarify the influence of 5-HTTLPR pretesting on relapse or recurrence rates. Furthermore, the findings from the performed review have shown that even 5-HTTLPR genotype affects remission rate; the impact of this indicator alone on antidepressant response is quite modest.…”