Two different initial dosing regimens with clomipramine (CMI) were use
d to compare early response indicators and dose strategies. Thirty-two
inpatients with major depressive disorder were randomized in a double
-blind protocol. The pulse-loading group received 150 and 200 mg of CM
I on 2 consecutive evenings and then received a placebo for 8 days. Th
e traditional dosing group began at 50 mg of CMI followed by gradual i
ncreases every second day until 200 mg was reached. After 10 days, bot
h groups were placed on an adjustable dosing schedule of CMI, initiall
y set at 200 mg, for an additional 2 weeks. Significant drug effects w
ere noted on several sleep parameters demonstrating suppression of rap
id eye movement (REM) sleep. In the pulse-loading group, drug responde
rs were found to have a significantly faster and more robust rebound i
n REM sleep than nonresponders. Both measures of REM activity and REM
sleep time showed a significant difference between the groups. In addi
tion, a significant correlation was found between falling levels of th
e desmethyl-clomipramine metabolite of CMI and REM sleep activity duri
ng the rebound phase. The clinical and theoretical implications of the
se findings are discussed.