Clomipramine in obsessive-compulsive disorder: clinical response and plasma levels

Two related data sets are presented that point to a specific pharmacological effect and support a predominantly serotonergic mediation of clomipramine's antiobsessional effect. A significant placebo versus clomipramine contrast from both the between- and within-group perspectives was found in 25 patients with moderate to severe obsessive-compulsive disorder of at least 2 years' duration and no evidence of depression who completed a double-blind, placebo-controlled, 10-week study. There was no significant improvement in the placebo group, six of whom subsequently improved with clomipramine. Analysis of the clinical significance of pharmacotherapy and the relationship between outcome and plasma drug concentrations in 33 obsessive-compulsive disorder patients treated with clomipramine (239.4 +/- 57.0 mg/day) revealed that 47% of the patients were rated in the subclinical range with one third of the sample being virtually symptom-free. Plasma levels of clomipramine, but not N-desmethylclomipramine, correlated significantly with posttreatment outcome measures, with responders having significantly higher clomipramine levels and a trend toward lower desmethylclomipramine ratios.