Kales A, Bixler E O, Vela-Bueno A, Soldatos C R, Manfredi R L
Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey.
J Clin Pharmacol. 1987 Jul;27(7):508-15. doi: 10.1002/j.1552-4604.1987.tb03058.x.
Alprazolam was evaluated in chronic insomniacs in a 1-mg bedtime dose. The 16-night sleep laboratory protocol included four placebo-baseline nights followed by seven nights of drug administration and five placebo-withdrawal nights. On the first three drug nights (nights 5 to 7), the drug was highly effective in inducing and maintaining sleep with this short-term use. By the end of the one week of administration (nights 9 to 11), however, the drug had lost about 40% of its efficacy. During drug use, one subject reported some difficulty in controlling expression of inappropriate emotions when interacting with others, which suggested the presence of disinhibition. On the third night following drug termination, there was a significant increase in sleep difficulty above baseline levels (rebound insomnia). This worsening was of comparable magnitude to the peak improvement of sleep with drug administration. Thus, the clinical utility of alprazolam when administered to insomniac patients appears to be limited because of a relatively rapid development of tolerance and possible disinhibitory reactions during drug use and the occurrence of rebound insomnia following withdrawal.
对慢性失眠症患者使用阿普唑仑进行评估，睡前剂量为1毫克。为期16晚的睡眠实验室方案包括四个安慰剂基线夜，随后是七个给药夜和五个安慰剂撤药夜。在前三个给药夜（第5至7夜），这种短期使用的药物在诱导和维持睡眠方面非常有效。然而，到给药一周结束时（第9至11夜），该药已失去约40%的疗效。在用药期间，一名受试者报告在与他人互动时难以控制不适当情绪的表达，这表明存在脱抑制现象。在停药后的第三个晚上，睡眠困难较基线水平显著增加（反弹性失眠）。这种恶化程度与用药时睡眠改善的峰值相当。因此，阿普唑仑用于失眠症患者时的临床效用似乎有限，因为耐受性相对较快发展，用药期间可能出现脱抑制反应，以及撤药后出现反弹性失眠。
