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.
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
Correspondence to Tania Marcourakis, PhD, Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Science, University of São Paulo, Av. Prof. Lineu Prestes, 580 Bloco 13B, CEP: 05508-900, São Paulo (SP), Brazil Tel/fax: +55 11 3091 1504; e-mail: firstname.lastname@example.org
Received May 27, 2014
Accepted September 4, 2014