Drug metabolizing enzymes pharmacogenetic variation-informed antidepressant therapy approach for common mental...

Currently, 30-50 % of individuals with depression and 40 % with anxiety-collectively referred to as common mental disorders (CMDs), exhibit inadequate responses to antidepressant treatments.

To assess the effectiveness and safety of drug-metabolizing enzyme pharmacogenetic variation informed treatment (PGxIT) versus usual antidepressant treatment (UT) in patients with CMDs.

A literature search was conducted in the MEDLINE, Scopus, and Cochrane Library databases from inception until January 30, 2024.

Studies were selected based on CMD diagnoses, reporting on the genetic variations of drug-metabolizing enzyme (DME) genes in relation to antidepressants, involving PGxIT and UT groups with human subjects, and published in English.

Data extraction and quality assessment were performed independently by two authors. A pooled risk ratio (RR) with 95 % CI was estimated using both random and fixed-effect models, and heterogeneity was assessed using Cochran's Q test and the I² statistic. The publication bias of eligible studies was assessed using post hoc Doi plots and the LFK index.

This systematic review included 18 studies (n = 7021). The PGxIT demonstrated greater efficacy in the remission of symptoms of depressive disorder at 8 weeks (RR 1.523 [95 % CI: 1.255-1.843]; I² = 48 %) and 12 weeks (RR 1.631 [95 % CI: 1.001-2.657]; I² = 86 %; p < 0.01), and symptoms of anxiety disorder compared to UT. Additionally, the risk of adverse drug events (ADEs) was significantly lower in the PGxIT group (RR = 0.65 [95 % CI: 0.52-0.82]; I² = 0 %) than in the UT group. The certainty of evidence for both outcomes was moderate.

This systematic review and meta-analysis suggest that pharmacogenetically guided antidepressant treatment, based on genetic variation in drug-metabolizing enzymes, is associated with superior efficacy in the remission of symptoms for patients with depressive disorders and a reduction in ADEs compared to usual treatment and the findings of the systematic review for remission in anxiety disorders indicate that, PGx guided treatment is also associated with increased remission of symptoms in anxiety disorders compared to usual treatment.