Efficacy of pharmacogenetic (PGx)-guided antidepressant treatment on functional outcomes and quality of life in adults with anxiety and affective disorders: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to estimate the efficacy of pharmacogenetic (PGx)-guided antidepressant treatment compared to treatment as usual (TAU) on functional outcomes and quality of life (QoL) in people with anxiety and affective disorders. A PRISMA-compliant systematic search was performed up to 26/06/2025 to identify relevant prospective, randomised controlled trials (RCTs) in seven databases. The revised tool for Risk of Bias (RoB2) was used to assess the methodological qualities of the included studies (PROSPERO CRD42024518683). Of 2774 records, six studies were included comprising 2285 adult patients (PGx group: n = 1395, Mean age = 48.14 years; 55.68 % females; TAU group: n = 890, Mean age = 47.83 years, 58.22 % females). Three studies were included in random-effect meta-analyses. In these, PGx-guided antidepressant treatment significantly decreased functional disability, measured by the Sheehan Disability Scale/Inventory (SDS/I), compared to TAU (k = 3, Mean Difference = -2.85, SE = 1.32 [95 % CI: -5.44, -0.26], p = .031). The Hartung-Knapp adjustment of p-values yielded non-significant effects. Individually, one of these three studies reported a significant effect of PGx-guided treatment on overall SDS score, one on SDI Perceived Social Support partial score, and one no effect. Risk for bias was rated high for one study, with some concerns for the other five. Due to the small number of included trials, our ability to conduct analyses of heterogeneity, moderators and publication bias was limited. Nonetheless, our results suggest that PGx-guided antidepressant treatment may improve functioning in people with anxiety and affective disorders.