Early response patterns associated with successful clomipramine treatment.

Two different initial dosing regimens with clomipramine (CMI) were compared with particular attention to early response indicators. Thirty-two inpatients with major depressive disorder were randomized in a double-blind protocol. The pulse-loading (P-L) group received 150 and 200 mg of CMI on two consecutive evenings, then placebo for 8 days; the traditional group began at 50 mg, followed by gradual increases every second day until 200 mg was reached. Both groups were then placed on an adjustable dosing schedule of CMI, initially set at 200 mg for an additional 2 weeks. After the completion of P-L, the improvement in scores on the Hamilton Rating Scale for Depression across protocol days 7 to 13 (the P-L placebo period) was equivalent for both dosage regimens and was significantly associated with therapeutic response at the end of the study (p = 0.0186). Desmethylclomipramine levels were significantly greater in P-L nonresponders (p = 0.0039), and a ratio of desmethylclomipramine/CMI of 2 or more after P-L was strongly associated with failure to respond to CMI (p = 0.02). Early, acute responses and assessments of metabolism observed with targeted doses of CMI may be predictive of later successful treatment.