Influence of combined CYP2C19 and CYP2D6 phenotypes on adverse drug reactions in patients with major depressive disorder: a clinical cohort study

Variants in cytochrome P450 enzymes are known risk factors for developing adverse drug reactions (ADR). Most antidepressants (AD) are simultaneously metabolized by major or minor pathway of CYP2C19 and CYP2D6, resulting in a complex interplay of metabolites. This study is one of the first to investigate and demonstrate the combined CYP 2C19/2D6 functional metabolic status as a risk factor for ADR in AD treatment of major depressive disorder. Most prescribed AD venlafaxine underwent subgroup analysis. Significantly more ADR in non-normal metabolizers (nNM) for one or both CYP enzymes compared with normal metabolizers (p = 0.039) were observed. Both slow (PM and IM) and rapid metabolizers (RM and UM) were affected. There were non-significant trends for CYP2C19 RM and UM with ADR in venlafaxine, which may be avoided in CYP2C19 nNM. More research is required to identify risk variants for personalized and safe AD treatment.