Clomipramine and Exposure for Compulsive Rituals: II. Plasma Levels, Side Effects and Outcome

Forty obsessive-compulsive ritualizers received nightly placebo or clomipramine up to 225 mgs nocte for 8 months, and received behavioural treatment (exposure in vivo) from weeks 4 to 10. Plasma concentrations of clomipramine and its primary metabolite N-desmethylclomipramine steadily increased over the first 4 weeks of treatment after which they remained relatively steady. Plasma levels correlated significantly with dose and with outcome but not with side effects. Patients with plasma clomipramine levels in the range 100–250 ng/ml and N-desmethylclomipramine levels between 230–550 ng/ml were found to improve significantly more than patients outside these ranges, thus suggesting a therapeutic window for clomipramine and its primary metabolite.