Symptomatic hypotension with venlafaxine-benzodiazepine interaction

Venlafaxine is an effective antidepressant drug that is chemically distinct from other antidepressants. Alprazolam is a triazolobenzodiazepine and diazepam is a 2-ketobenzodiazepine. Benzodiazepines are frequently co-administered with antidepressants, a fact that brings the problem of drug-drug interactions, because they are metabolized by various cytochrome pigment (CYP) 450 isoenzymes. We present three cases who developed symptomatic hypotension with co-administration of venlafaxine and benzodiazepines, namely, alprazolam and diazepam. In all cases, arterial blood pressure returned to normal with the discontinuation of pharmacological treatment. Although there is insufficient evidence, a substantial inhibition of CYP 3A3/4 by venlafaxine could result in a meaningful increase in plasma levels of venlafaxine, O-desmethylvenlafaxine, alprazolam and diazepam, particularly in patients who are CYP 2D6 deficient. A less likely explanation for the interaction between venlafaxine and benzodiazepines would be CYP 3A3/4 deficiency, which might potentiate the increase in plasma levels of benzodiazepines, thereby increasing their adverse effect potential. Combination of venlafaxine and benzodiazepines may increase the incidence and severity of adverse effects of both drugs.