PHARMACOKINETIC FLUVOXAMINE - CLOMIPRAMINE INTERACTION WITH FAVORABLETHERAPEUTIC CONSEQUENCES IN THERAPY-RESISTANT DEPRESSIVE PATIENT

We describe the case of a depressive patient who was a rapid metaboliz er of CYP2D6 substrates and a heavy smoker, and who did not respond to several courses of treament with antidepressants, as a result of unus ually low drug-plasma levels. During hospitalization, he did not impro ve after treatment with clomipramine (150-225 mg/day during three week s), but showed a response within four days after addition of fluvoxami ne (100 mg/day). Plasma levels of clomipramine and desmethylclomiprami ne changed from 58 ng/ml and 87 ng/ml to 223 ng/ml and 49 ng/ml respec tively one week after addition of fluvoxamine. Present knowledge of th e role of cytochrome P-450 isozymes, such as CYP1A2, CYP2C19, CYP2D6, and CYP3A4, in the metabolism of psychotropic drugs as well as therape utic drug-plasma level monitoring may thus help to determine individua l treatment.