EARLY RESPONSE PATTERNS ASSOCIATED WITH SUCCESSFUL CLOMIPRAMINE TREATMENT

Two different initial dosing regimens with clomipramine (CMI) were com pared with particular attention to early response indicators. Thirty-t wo inpatients with major depressive disorder were randomized in a doub le-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 tr aditional group began at 50 mg, followed by gradual increases every se cond 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 addi tional 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 a nd was significantly associated with therapeutic response at the end o f the study (p = 0.0186). Desmethylclomipramine levels were significan tly greater in P-L nonresponders (p = 0.0039), and a ratio of desmethy lclomipramine/CMI of 2 or more after P-L was strongly associated with failure to respond to CMI (p = 0.02). Early, acute responses and asses sments of metabolism observed with targeted doses of CMI may be predic tive of later successful treatment.