Pharmacogenetics of antidepressant response

Abstract

There is substantial interindividual variation in response to antidepressants. Family and twin studies suggest that genetic variation may, at least in part, explain these differences. Pharmacogenetic research attempts to identify the genetic variants associated with antidepressant response to both understand the mechanism of action of pharmacotherapies and to predict outcome. Genes implicated in the pharmacokinetics or pharmacodyamics of antidepressants have been shown to predict response; however, the failure of some findings to replicate has been disappointing. More recent hypothesis-free approaches have identified novel candidates for antidepressant response. However, results have been considerably modest and suggest that treatment outcome is determined by multiple genetic variants of small effect. The small effect sizes of genetic variants and heterogeneity between studies have significantly hindered attempts to find robust genetic predictors of response to antidepressants. To allow the direct comparison of findings, future pharmacogenetic studies should employ standardized methodology and consider using intermediate phenotypes of response, such as neurogenesis, that may more closely reflect the mechanism of action of antidepressants.

Keywords::

• adverse drug
• antidepressant response
• antidepressants
• depression
• pharmacogenetics
• pharmacogenomics
• reactions
• SSRI
• tricyclic antidepressant

Financial & competing interests disclosure

Robert Keers is funded by a Medical Research Council (MRC) PhD Studentship to the MRC SGDP Centre at the Institute of Psychiatry, King’s College London and reports no conflicts of interest. Kathy Aitchison has received consultancy fees and honoraria for participating in expert panels from pharmaceutical companies including Lundbeck and GlaxoSmithKline. 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.