Association Between CYP450 Polymorphisms and Treatment Outcomes of Escitalopram and Venlafaxine in Patients with Post Stroke Depression

Background: Genetic polymorphisms in drug metabolism play an important role in the wide inter-individual variability in antidepressant efficacy. This study aimed to determine whether cytochrome P450 2C19 ( CYP2C19 ) and cytochrome P450 2D6 ( CYP2D6 ) genotypes predict treatment response to escitalopram (ESC) and venlafaxine (VEN), respectively, in patients with post-stroke depression (PSD). Methods: In this single-center prospective observational study, 313 acute stroke patients with PSD were consecutively enrolled and received ESC or VEN for 8 weeks. Efficacy was assessed using the 17-item Hamilton Depression Scale (HAMD-17). The primary outcome was the change in HAMD-17 score from baseline to week 8; secondary outcomes were response (≥ 50% reduction) and remission (score ≤ 7). Patients were stratified by CYP2C19 and CYP2D6 genotypes into fast- and slow-metabolizer subgroups. Subgroup comparisons utilized χ2 -tests and Mann–Whitney U -tests. Results: At week 8, among 148 ESC-treated patients, CYP2C19 genotypes were distributed as poor/intermediate metabolizers (PM/IM) 82 (55.4%) and normal/rapid metabolizers (NM/RM) 64 (43.2%); among 113 VEN-treated patients, CYP2D6 genotypes showed marked imbalance (only 2 IM, 111 NM). No significant difference was found between ESC PM/IM and NM/RM subgroups in HAMD‑17 reduction (median: 10 vs 11, P =0.434), response (61.0% vs 69.7%, P =0.269), or remission (48.8% vs 51.5%, P =0.741). For patients treated with VEN, there was a significant imbalance in the distribution of CYP2D6 genotypes, which prevented us from further analyzing the association between CYP2D6 gene polymorphisms and the efficacy of VEN. Conclusion: No significant effect of CYP2C19 genetic polymorphism on ESC efficacy was observed in this study. These findings underscore the need for further exploration into the clinical utility of pharmacogenetics. Future antidepressant treatment should prioritize cost-effective, pragmatic approaches over costly genetic testing alone. Keywords: pharmacogenomics, cytochrome P450 enzymes, antidepressant, post-stroke depression