Pharmacogenomic testing and personalized treatment of depression

Abstract

Background: There is wide variation in antidepressant efficacy and tolerability during the treatment of major depressive disorder, a brain disease associated with significant morbidity and mortality risk. The ability to rapidly identify optimal treatment, thereby shortening the time to symptomatic remission, could reduce these risks and associated costs.

Content: Up to 42% of variance in antidepressant response is associated with common genetic variation, and there are over 10 psychotropic medications for which the US Food and Drug Administration-approved labeling reflects a genetic test. Most published studies have examined functional variations in genes of the cytochrome p450 system, relevant to metabolism of many antidepressants. However, there are few data supporting the clinical usefulness of specific pharmacogenetic tests. Randomized trials and cost-effectiveness studies are emerging, but larger-scale studies are needed. Specific challenges in translating genetic association results to clinical practice include need for replication to address risk of type I error, overestimation of effect sizes, absence of data from generalizable cohorts, and absence of comparative data that would suggest one specific intervention over another. Several opportunities to accelerate development and validation of new tools for stratification remain, including integration of these tests with clinical data or other biomarkers and application of electronic health records for test development and investigation.

Summary: Although common genetic variation, particularly in genes of the cytochrome p450 system, has been associated with antidepressant response, evidence that this variation may be successfully applied to guide treatment selection is just emerging. Larger-scale studies facilitated by informatics tools will clarify the usefulness of such tests.