CYP2D6 and CYP2C19 ultrarapid metabolisms are associated with suicide attempts in schizophrenia

Abstract

Introduction: Genetic polymorphisms in genes encoding enzymes metabolizing psychotropics drugs result in various isoenzymes with different catalytic efficacies. Of particular interest, some of these isoenzymes are highly catalytic leading to an Ultra-rapid metabolism (UM) of their substrate medication, which in turn results in lower medication concentrations and possibly poor clinical outcomes, including a higher risk for suicidal behavior. In this study, we investigate the role of CYP2D6 (metabolizing most antidepressant medications) and CYP2C19 (important in metabolizing antipsychotics) UM isoenzymes on suicidal behavior among a cohort of patients with schizophrenia.Methods: 178 patients diagnosed with schizophrenia were recruited from the day hospital of a regional psychiatric academic hospital. Lifetime suicide attempts were compared between groups of patients stratified according to their enzymatic profile. Several socio-demographics and clinical covariates were controlled for.Results: Among the 178 patients, 16 and 44 were UM as determined by their CYP2D6 and CYP2C19 genotype respectively. Univariate analysis showed a significant association between suicidal attempts and CYP2D6 and CYP2C19 UM status (p = 0.041 and p = 0.029 respectively). These associations remained significant in multivariate analyses (adjusted for age, sex, dose exposure and antidepressant use…) for both CYP2D6 (p = 0.020, OR = 4,096, 95% CI [1.25-13.48]) and CYP2C19 (p = 0.016, OR = 2.680, 95% CI [1.21-5.95]).Conclusion: This study suggests that the UM phenotypes for both CYP2D6 and CYP2C19 are associated with an increased risk for suicide attempts in patients with schizophrenia.