Bg. Pollock et al., EARLY RESPONSE PATTERNS ASSOCIATED WITH SUCCESSFUL CLOMIPRAMINE TREATMENT, Journal of clinical psychopharmacology, 13(6), 1993, pp. 442-447
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.