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

Cytochrome P450 2D6 (CYP2D6) is a polymorphic enzyme that influences antidepressant metabolism. This retrospective 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 = 21), or normal metabolizers (NM, n = 73). Effectiveness and tolerability were assessed from admission to discharge (~4 weeks). Hamilton Depression Rating Scale (HAM-D) score reduction was the primary outcome; tolerability was measured using the Toronto Side Effects Scale (TSES). Compared with NMs, HAM-D score reductions were 4.3 and 9.0 points lower in IMs and PMs. TSES scores were 1.3 and 2.3 points higher in IMs and PMs, respectively. Central nervous system and gastrointestinal effects were more frequent in IMs and PMs; sexual dysfunction did not differ. Reduced CYP2D6 activity was associated with poorer outcomes, indicating the potential usefulness of CYP2D6 genotyping in MDD.