Pharmacokinetic fluvoxamine-clomipramine interaction with favorable therapeutic consequences in therapy-resistant depressive patient.
We describe the case of a depressive patient who was a rapid metabolizer of CYP2D6 substrates and a heavy smoker, and who did not respond to several courses of treatment with antidepressants, as a result of unusually low drug-plasma levels. During hospitalization, he did not improve after treatment with clomipramine (150-225 mg/day during three weeks), but showed a response within four days after addition of fluvoxamine (100 mg/day). Plasma levels of clomipramine and desmethylclomipramine changed from 58 ng/ml and 87 ng/ml to 223 ng/ml and 49 ng/ml respectively one week after addition of fluvoxamine. Present knowledge of the role of cytochrome P-450 isozymes, such as CYP1A2, CYP2C19, CYP2D6, and CYP3A4, in the metabolism of psychotropic drugs as well as therapeutic drug-plasma level monitoring may thus help to determine individual treatment.
Conus
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P
Département universitaire de psychiatrie adulte, Site de Cery, Prilly-Lausanne, Switzerland.
Bondolfi
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G
Eap
C B
CB
Macciardi
F
F
Baumann
P
P
D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002997:Clomipramine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D004347:Drug Interactions; D004351:Drug Resistance; D004565:Electroconvulsive Therapy; D016666:Fluvoxamine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012907:Smoking / Q000378:metabolism
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D019389:Cytochrome P-450 CYP2D6; D002997:Clomipramine; D016666:Fluvoxamine