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.
Subject(s)
Antidepressive Agents, Tricyclic/pharmacokinetics , Clomipramine/pharmacokinetics , Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Adult , Antidepressive Agents, Tricyclic/blood , Biotransformation , Brazil , Clomipramine/analogs & derivatives , Clomipramine/blood , Dealkylation , Drug Monitoring , Female , Humans , Male , Middle Aged , Obsessive-Compulsive Disorder/blood , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/physiopathology , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors/blood , Single-Blind Method , Treatment OutcomeABSTRACT
Several placebo-controlled trials have shown the efficacy of clomipramine (CMI) in panic disorder. However, none has investigated the relationship between CMI, and desmethylclomipramine (DCMI) plasma levels, and outcome. In this trial, 41 patients meeting the DSM-III-R criteria for panic disorder with/without agoraphobia received 50-200 mg of CMI daily in a single-blind, flexible dose regimen for 14 weeks. At the end of treatment, 97% of the patients were free of panic attacks. Patients were classified into two groups of improvement according to the panic symptom items of the 'Patient-Rated Anxiety Scale'. A repeated-measures analysis of variance suggested a significant association between outcome and serum DCMI level/daily dose ratio as well as total serum level/daily dose. Patients with intense improvement showed DCMI and total serum levels lower than those with moderate improvement. The results indicate the importance of monitoring clomipramine and desmethylclomipramine serum levels in this disorder.
Subject(s)
Antidepressive Agents, Tricyclic/blood , Antidepressive Agents, Tricyclic/therapeutic use , Clomipramine/analogs & derivatives , Clomipramine/blood , Clomipramine/therapeutic use , Panic Disorder/drug therapy , Adult , Female , Humans , Male , Middle Aged , Panic Disorder/psychology , Psychiatric Status Rating Scales , Single-Blind MethodABSTRACT
Las concentraciones plasmáticas de clomipramina y diazepam son medidas y correlacionadas con las dosis y respuesta terapéutica. Este es un estudio comparativo doble ciego entre clomipramina y diazepam en pacientes con Desorden de Pánico y Agorafobia. Se estudian 31 pacientes con diagnóstico de Desorden de Pánico y Agorafobia según DSM-III tratados en la Unidad de Pánico del Consultorio Externo del Hospital Psiquiátrico Dr. José Horwitz B. Los pacientes fueron evaluados clínicamente en las semanas 1, 4 y 8 después de iniciado el tratamiento. Los resultados sugieren que clomipramina es efectiva en dosis y concentraciones plasmáticas menores. Se encontró correlación lineal entre dosis y concentración plasmática en las semanas 4 y 8, no así en la semana 1, donde algunos pacientes con bajas dosis presentaron concentraciones plasmáticas elevadas. No se encontró correlación entre concentración plasmática y evaluación clínica. Las concentraciones plasmáticas de diazepam mostraron correlación lineal con las dosis sólo en la primera semana de tratamiento; lo cual no es concordante con lo descrito en la literatura. Se requieren nuevos estudios para confirmar estos hallazgos