title: Clomipramine demethylation rate is important on the outcome of obsessive-compulsive disorder treatment.
abstract: The aim of this study was to investigate the influence of demethylation rate on the outcome of obsessive-compulsive disorder patients treated with clomipramine. Eighteen patients meeting the DSM-IV criteria for obsessive-compulsive disorder received 150-300 mg of clomipramine daily in a single-blind design for 12 weeks. The patients were evaluated with the Clinical Global Impression scale and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Clinical assessment and serum measurements of clomipramine and desmethylclomipramine were carried out at baseline and after 3, 6, 8, 10, and 12 weeks. A greater improvement in Clinical Global Impression scale rating was associated with a lower desmethylclomipramine/daily dose and the total clomipramine and desmethylclomipramine/daily dose. Moreover, an improved response on the YBOCS-obsession score was associated with higher serum levels of clomipramine and the total clomipramine and desmethylclomipramine/daily dose. Patients with a greater reduction in baseline YBOCS rating had a lower desmethylclomipramine/clomipramine ratio. These data suggest that a lower demethylation rate correlates with better clinical outcome.
authors.affiliation: aDepartment of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Science bDepartment and Institute of Psychiatry cDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo dLIM-23, Laboratory of Psychopharmacology of the Clinical Hospital, Medical School of the University of São Paulo, São Paulo, Brazil.
authors.forename: Tania
authors.initials: T
authors.lastname: Marcourakis
authors.forename: Márcio A
authors.initials: MA
authors.lastname: Bernik
authors.forename: Francisco
authors.initials: F
authors.lastname: Lotufo Neto
authors.forename: Roseli
authors.initials: R
authors.lastname: Gedanke Shavitt
authors.forename: Clarice
authors.initials: C
authors.lastname: Gorenstein
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D001711:Biotransformation; D001938:Brazil; D002997:Clomipramine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D003640:Dealkylation; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D017367:Selective Serotonin Reuptake Inhibitors; C012273:desmethylclomipramine