Association between CYP2D6 genotype and treatment effectiveness and safety in 99 hospitalized patients with major depressive disorder - a retrospective cohort study

Cytochrome P450 2D6 (CYP2D6) is a polymorphic enzyme that affects antidepressant metabolism. This retrospective hospital-based cohort study investigated the association between CYP2D6 genotype and treatment outcomes in 99 hospitalized patients with major depressive disorder (MDD) in Belgrade, Serbia. Patients were classified as poor (PM, n = 5), intermediate (IM, n = 30), or normal metabolizers (NM, n = 64). Effectiveness and tolerability were assessed from admission to discharge (approximately four weeks). Effectiveness was measured using the reduction in Hamilton Depression Rating Scale (HAM-D) score, while tolerability was measured using the Toronto Side Effects Scale (TSES). Compared with NMs, HAM-D score reductions were 5.1 and 9.5 points lower, while TSES scores were 0.8 and 2.3 points higher in IMs and PMs, respectively, with higher prevalence of CNS and gastrointestinal side effects among IMs and PMs. Reduced CYP2D6 activity was associated with poorer antidepressant treatment outcomes supporting the potential clinical utility of CYP2D6 genotyping for treatment individualization.