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

CYP2C19

CYP2C19 and CYP2D6 metabolizer status and response to escitalopram and venlafaxine

Single-centre prospective observational study consecutively enrolling 313 patients in the acute phase of stroke with post-stroke depression, treated for eight weeks with escitalopram or venlafaxine. Efficacy was measured by change in HAMD-17 score from baseline to week 8, with response (≥ 50% reduction) and remission (score ≤ 7) as secondary outcomes, patients being stratified into slow and fast metabolizers for CYP2C19 and CYP2D6. Among 148 escitalopram-treated patients, 82 (55.4%) were poor or intermediate metabolizers and 64 (43.2%) normal or rapid metabolizers for CYP2C19: no difference was seen 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 venlafaxine, the CYP2D6 genotype distribution was too imbalanced among the 113 treated patients (2 intermediate metabolizers versus 111 normal) to allow any analysis. The authors conclude that CYP2C19 polymorphism had no effect on escitalopram efficacy in this population.

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

A well-conducted negative study retains its value, provided one reads what it actually tested: antidepressant efficacy at eight weeks, not tolerability or plasma exposure, whereas the CPIC recommendation for the CYP2C19-escitalopram pair concerns dose adjustment and adverse-effect risk in poor metabolizers. The absence of an efficacy difference therefore does not disqualify genotyping; it is a reminder that a pharmacokinetic genotype predicts exposure, not clinical response in a condition where treatment effect also depends on neurological recovery. The venlafaxine arm, with 2 intermediate metabolizers among 113 patients, is uninterpretable and should not have been presented as a study objective.

Analysis by Dr Thibaut Benquey