Antidepressant drug interactions and the cytochrome P450 system: a critical appraisal

Evaluation of the inhibitory effects of antidepressant drugs on hepatic cytochrome P450 isoenzymes can allow clinicians to predict drug interactions occurring via this mechanism a priori. The magnitude and clinical relevance of these drug interactions are dependent on many factors including concentration of the isoenzyme inhibitor, contribution of active metabolites with isoenzyme inhibitory activity, and toxicity of the concomitant medication. This review summarizes information to date regarding the inhibitory potency of fluoxetine, fluvoxamine, paroxetine, sertraline, nefazodone, and venlafaxine on five isoenzyme systems: CYP2D6, CYP3A3/4, CYP1A2, CYP2C9, and CYP2C19. Both in vitro and in vivo isoenzyme inhibition data are presented and correlated to drug interactions of clinical relevance.