Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta-Analysis of Prospective, Controlled Clinical Trials

Clinical Pharmacology & Therapeutics Manuscript
Authors Lisa C. Brown, Joseph D. Stanton, Kanika Bharthi, Abdullah Al Maruf, Daniel J. Müller, Chad A. Bousman

Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder. We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4767 patients were analyzed, including 10 randomized controlled trials and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2395) were 1.41 (95% CI: 1.15 – 1.74, p = 0.001) more likely to achieve remission compared to those that received unguided antidepressant therapy (n = 2372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13 – 1.88) and 1.26 (95% CI: 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with major depressive disorder. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.