Interaction of modafinil and clomipramine as comedication in a narcoleptic patient

Modafinil is a psychostimulant compound that is just now becoming available in many countries for treatment of narcoleptic and hypersomnic patients. Whereas sleep attacks and drowsiness can be effectively improved, the drug does not sufficiently reduce cataplectic seizures. It therefore is often used in combination with tricyclic antidepressant medication, although little is known about the possible interactions. This case report describes a narcoleptic patient chronically treated with clomipramine who started receiving modafinil. The blood concentrations of clomipramine and its metabolite showed a significant dose-dependent and reversible increase under modafinil. Since the patient was genotypically and phenotypically a cytochrome P450 2D6 poor metabolizer, the authors attribute the relevant pharmacokinetic interaction to another clomipramine-metabolizing enzyme.