Kupfer D J, Pollock B G, Perel J M, Miewald J M, Grochocinski V J, Ehlers C L
Dept. of Psychiatry, WPIC, Pittsburgh, PA 15213-2593, USA.
Psychiatry Res. 1994 Nov;54(2):161-75. doi: 10.1016/0165-1781(94)90004-3.
Two different initial dosing regimens with clomipramine (CMI) were used 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 CMI on 2 consecutive evenings and then received a placebo for 8 days. The traditional dosing group began at 50 mg of CMI followed by gradual increases every second day until 200 mg was reached. After 10 days, both groups were placed on an adjustable dosing schedule of CMI, initially set at 200 mg, for an additional 2 weeks. Significant drug effects were noted on several sleep parameters demonstrating suppression of rapid eye movement (REM) sleep. In the pulse-loading group, drug responders were found to have a significantly faster and more robust rebound in REM sleep than nonresponders. Both measures of REM activity and REM sleep time showed a significant difference between the groups. In addition, a significant correlation was found between falling levels of the desmethylclomipramine metabolite of CMI and REM sleep activity during the rebound phase. The clinical and theoretical implications of these findings are discussed.
使用两种不同的氯米帕明（CMI）初始给药方案来比较早期反应指标和剂量策略。32名重度抑郁症住院患者按双盲方案随机分组。脉冲负荷组在连续两个晚上分别接受150毫克和200毫克的CMI，然后接受8天的安慰剂治疗。传统给药组从50毫克CMI开始，每隔一天逐渐增加剂量，直至达到200毫克。10天后，两组均采用可调整的CMI给药方案，初始设定为200毫克，再持续2周。在几个睡眠参数上观察到显著的药物效应，表明快速眼动（REM）睡眠受到抑制。在脉冲负荷组中，发现药物反应者的REM睡眠反弹比无反应者显著更快且更强烈。REM活动和REM睡眠时间的测量在两组之间均显示出显著差异。此外，在反弹阶段，CMI的去甲氯米帕明代谢产物水平下降与REM睡眠活动之间存在显著相关性。讨论了这些发现的临床和理论意义。
