EFFECT OF PULSE LOADING WITH CLOMIPRAMINE ON EEG SLEEP

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.