Moderate
Probable
Description
Carbamazepine substantially reduces duloxetine plasma levels through CYP1A2 and CYP3A4 induction, risking loss of antidepressant efficacy.
Mechanism
Carbamazepine induces CYP1A2 and CYP3A4, the primary enzymes responsible for duloxetine oxidative metabolism, significantly increasing its clearance.
Clinical Significance
Duloxetine concentrations may drop well below effective levels; depression or pain relapse is a realistic clinical outcome.
Management
Closely monitor clinical response; consider antidepressants less susceptible to enzyme induction (e.g., venlafaxine) if carbamazepine is required.