Individualized pharmacogenomics for depressive episodes: A narrative review.

Pharmacokinetic genes CYP2D6 and CYP2C19 (and, more modestly, CYP3A4 and CYP1A2) drive antidepressant exposure; pharmacodynamic genes remain exploratory.

This narrative review synthesizes the contribution of pharmacogenomics to depressive episodes in major depression and bipolar disorder, drawing on guideline resources (CPIC, PharmGKB, DPWG). Robust, replicated evidence supports the clinical use of pharmacokinetic genes CYP2D6 and CYP2C19, with genotype-informed prescribing recommendations improving drug exposure and reducing adverse effects, particularly for SSRIs; CYP3A4 and CYP1A2 contribute to metabolism but with limited formal recommendations. Pharmacodynamic genes (COMT, FKBP5, HTR2A, SLC6A4, MTHFR) and polygenic risk scores remain future avenues, lacking predictive performance for routine use. Randomized trials and meta-analyses (GUIDED, PRIME Care, IGNITE) show moderate benefit of guided prescribing on remission and tolerability.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This review usefully clarifies the evidence hierarchy in precision psychiatry, distinguishing actionable genes (CYP2D6, CYP2C19, covered by CPIC) from still-exploratory pharmacodynamic candidates. It rightly stresses that guided prescribing is an informative, not curative, adjunct whose benefit magnitude remains debated. A timely reminder to account for environmental modifiers (smoking, inhibitors) and the limits of polygenic scores outside European ancestry.

Analysis by Dr Thibaut Benquey