McLeod D R, Hoehn-Saric R, Labib A S, Greenblatt D J
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Clin Psychopharmacol. 1988 Apr;8(2):83-99.
Effects of a therapeutic dose of diazepam (15 mg daily), administered over a 6-week period, were assessed in nonanxious female volunteers. No acute effects of the 5-mg dose of diazepam on performance were observed, but two types of effects were observed on physiology: (1) direct changes on some measures (e.g., skin conductance) and (2) an absence or attenuation of changes expected on the basis of data obtained with a placebo group. The latter effect was found for systolic blood pressure both initially and again after 6 weeks of medication. When performance measured in the morning prior to the first 5-mg dose was compared with that of the morning prior to the last 5-mg dose, 6 weeks later, two types of impairment were found in the diazepam group: (1) decrements in performance (e.g., digit span) and (2) a failure to show expected improvement (e.g., DSST). Performance impairment due to reduced motivation was ruled out by a motivational component of the test battery. Performance tended to return to predrug levels 2 weeks after discontinuation of medication. When physiology was measured in the morning prior to the first dose of the day, 6 weeks of treatment produced decreases in skin conductance, diastolic blood pressure, and heart rate. Blood pressure and heart rate, but not skin conductance, returned to predrug levels 2 weeks after discontinuation of medication. Results of this study indicate that the long-term effects of diazepam can differ from the acute effects and that both acute and long-term effects can take at least two forms, depending upon the behavior or physiological process measured.
在无焦虑的女性志愿者中评估了连续6周给予治疗剂量地西泮(每日15毫克)的效果。未观察到5毫克剂量地西泮对行为表现的急性影响,但在生理方面观察到两种类型的影响:(1)对某些测量指标(如皮肤电导)的直接变化;(2)基于安慰剂组获得的数据预期的变化不存在或减弱。在用药初始及用药6周后,收缩压均出现了后一种效应。将用药6周后末次5毫克剂量服药前早晨的行为表现与首次5毫克剂量服药前早晨的行为表现相比较,地西泮组出现了两种类型的损害:(1)行为表现下降(如数字广度);(2)未表现出预期的改善(如数字符号替换测验)。测试组合中的动机成分排除了因动机降低导致的行为表现损害。停药2周后,行为表现倾向于恢复到用药前水平。当在每日首次服药前早晨测量生理指标时,6周的治疗使皮肤电导、舒张压和心率降低。停药2周后,血压和心率恢复到用药前水平,但皮肤电导未恢复。本研究结果表明,地西泮的长期效应可能与急性效应不同,且急性和长期效应至少都有两种形式,这取决于所测量的行为或生理过程。