Clinical effectiveness of pharmacogenomic-guided antidepressant treatment in adult major depressive disorder: systematic review and exploratory platform-aware meta-analysis

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• Picked for Psychiatry and Mental Health (top studies of the week, 19 July 2026).

Abstract

BACKGROUND: Combinatorial pharmacogenomic (PGx) tests aim to guide antidepressant selection and dosing in adult major depressive disorder (MDD), but available platforms differ in gene content, decision rules, clinical reporting, and implementation. Therefore, indiscriminate pooling across PGx platforms may obscure platform-specific effects. METHODS: We searched MEDLINE (PubMed), Embase, and APA PsycINFO from inception to 31 December 2025, screened reference lists, and conducted a formal update search on 14 April 2026 using the same search concepts and eligibility criteria. We included RCTs enrolling adults with MDD and comparing PGx-guided antidepressant prescribing versus treatment as usual (TAU)/unguided care. Two RCT-only quantitative syntheses were prespecified: (a) a primary platform-specific analysis restricted to GeneSight RCTs and (b) a secondary exploratory cross-platform analysis of other multigene PGx panels. Random-effects models were used; effects are reported as risk ratios (RRs). RESULTS: Eight RCTs were included. In the primary platform-specific GeneSight analysis (three trials), PGx-guided care increased response (RR 1.30, 95% CI 1.09-1.56; I2 = 0%) and remission (RR 1.53, 95% CI 1.19-1.97; I2 = 0%) within the prespecified 8-12-week acute window. In the secondary exploratory cross-platform analysis (five trials for response; four for remission), effects were heterogeneous and imprecise: response RR 1.18 (95% CI 0.91-1.54; I2 = 78%) and remission RR 1.18 (95% CI 0.77-1.80; I2 = 82%). CONCLUSIONS: In adult MDD, GeneSight-guided care was associated with modest short-term increases in response and remission within the available RCT evidence. Pooled effects across other multigene PGx panels were heterogeneous and imprecise. The platform-aware structure reflects differences in data availability, comparability, and internal validity, and it should not be interpreted as evidence of superiority of one commercial PGx platform over others. Evidence was limited by the small number of short-term RCTs, residual risk-of-bias concerns, and heterogeneity/imprecision in the secondary exploratory cross-platform analysis. Future trials should harmonize outcomes, follow-up, implementation reporting, and platform-specific decision-support descriptions to improve cross-platform comparability.

Abstract as published, via PubMed.