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Clomipramine demethylation rate is important on the outcome of obsessive-compulsive disorder treatment
Tania Marcourakis1, Márcio A Bernik, Francisco Lotufo Neto
1aDepartment 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.
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.
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