Abstract
Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants provide the most reliable actionable approach to guide choice and dosing of antidepressants in major depression to improve outcomes. We carried out a meta-analysis and meta-regression analyses of randomised controlled trials evaluating pharmacogenomic tests with CYP2D6 and CYP2C19 polymorphisms in major depression. A systematic review was conducted according to PRISMA and Cochrane guidelines to search several electronic databases. Logarithmically transformed odds ratios (OR) and confidence intervals (CI) for improvement, response and remission were calculated. A random-effects meta-analysis and meta-regression analyses were subsequently carried out. Twelve randomised controlled trials were included. Pharmacogenomic tests in the treatment of depression were more effective than treatment as usual for improvement (OR:1.63, CI: 1.19–2.24), response (OR: 1.46; CI: 1.16–1.85) and remission (OR: 1.85; CI: 1.23–2.76) with no evidence of publication bias. Remission was less favourable in recent studies. The results are promising but cautious use of pharmacogenomics in major depression is advisable. PROSPERO registration ID: CRD42021261143.
•P450 cytochromes CYP2D6 and CYP2C19 are heavily involved in the metabolism of commonly prescribed antidepressants.•Genomic variants of these enzymes can predict clinically relevant metabolic phenotypes with a direct impact on pharmacokinetic parameters and potentially explain up to 50% of adverse drug reactions.•This systematic review and meta-analysis appraised current evidence from randomised controlled studies that investigated a pharmacogenomic-guided approach which included CYP2D6 and CYP2C19 genomic variants.•The results support a cautious use of pharmacogenomics-based therapeutic approaches in major depression.