Hajak G, Clarenbach P, Fischer W, Rodenbeck A, Bandelow B, Broocks A, Rüther E
Department of Psychiatry, University of Göttingen, Germany.
Eur Arch Psychiatry Clin Neurosci. 1998;248(3):148-56. doi: 10.1007/s004060050032.
The effect of abrupt medication withdrawal (no-pill discontinuation) was investigated in 1507 insomniacs using the patients' self-ratings on visual analogue scales. Drug discontinuation followed a 28-day treatment period with either 7.5 mg zopiclone, 0.25 mg triazolam, 1.0 mg flunitrazepam, or placebo in a randomized, double-blind, parallel group, multicenter study in private practice. Deterioration below individual pretreatment values (no-pill baseline) in at least one of three subjective parameters of sleep quality (sleep latency, total sleep time, nocturnal awakenings) and three parameters of daytime well-being (morning freshness, daytime tiredness, anxiety) were defined as rebound. The number of patients with rebound (rebound rate) was analyzed for every day of a 2-week posttreatment period. The overall rebound rate was higher in the placebo group (p < or = 0.001) than in each group treated with active drugs. Rebound rates affecting sleep quality were higher for placebo than for zopiclone (p < or = 0.001) and for flunitrazepam (p < or = 0.05). Rebound rates were smaller for zopiclone (p < or = 0.001) and flunitrazepam (p < or = 0.01) than for triazolam. Rebound in at least one item per day appeared in 21.5% (sleep quality) and 25.5% (daytime well-being) of the patients. Rebound decreased with increasing numbers of items of sleep quality or daytime well-being. Patients who did not respond to treatment showed higher rebound rates than those who were treatment responders (p < or = 0.001). Concerning treatment nonresponders, highest rebound was seen in the placebo group, whereas rebound was lowest in placebo responders. These results show that pill discontinuation itself may worsen sleep and daytime well-being in the sense of a rebound phenomenon. Furthermore, the number of patients with rebound remained at a high and varying level during the whole posttreatment period. This result indicates that a deterioration of sleep after drug withdrawal is not apparent during a few days but may last for longer periods in some patients and is modified by marked night-to-night variations.
在一项针对1507名失眠患者的研究中，使用视觉模拟量表上患者的自我评分，对突然停药（不服药停药）的影响进行了调查。在一项私人诊所的随机、双盲、平行组、多中心研究中，患者在接受为期28天的治疗后停药，治疗药物分别为7.5毫克佐匹克隆、0.25毫克三唑仑、1.0毫克氟硝西泮或安慰剂。睡眠质量的三个主观参数（入睡潜伏期、总睡眠时间、夜间觉醒次数）和日间幸福感的三个参数（早晨清醒程度、日间疲劳感、焦虑程度）中至少有一项低于个体治疗前值（不服药基线）被定义为反跳。在治疗后2周的每一天，分析出现反跳的患者数量（反跳率）。安慰剂组的总体反跳率高于各活性药物治疗组（p≤0.001）。安慰剂组影响睡眠质量的反跳率高于佐匹克隆组（p≤0.001）和氟硝西泮组（p≤0.05）。佐匹克隆组（p≤0.001）和氟硝西泮组（p≤0.01）的反跳率低于三唑仑组。21.5%的患者（睡眠质量方面）和25.5%的患者（日间幸福感方面）出现至少一项每日反跳。反跳随着睡眠质量或日间幸福感项目数量的增加而减少。未对治疗产生反应的患者的反跳率高于治疗有反应的患者（p≤0.001）。关于治疗无反应者，安慰剂组的反跳最为明显，而安慰剂有反应者的反跳最低。这些结果表明，停药本身可能会在反跳现象的意义上使睡眠和日间幸福感恶化。此外，在整个治疗后期间，出现反跳的患者数量一直处于较高且变化的水平。这一结果表明，停药后睡眠恶化并非在几天内就很明显，而是在某些患者中可能持续更长时间，并且会因明显的夜间差异而有所改变。
