van Laar M W, Volkerts E R, van Willigenburg A P
Netherlands Institute for Drugs and Doping Research, University of Utrecht, The Netherlands.
J Clin Psychopharmacol. 1992 Apr;12(2):86-95.
Two groups of 12 outpatients each (six men and six women) with generalized anxiety disorder, participated in this study. Each patient was treated single-blind with placebo during the first 7 days (baseline), followed by a double-blind drug treatment period of 4 consecutive weeks (active) and ending again with 7 days single-blind placebo treatment (washout). One group received buspirone 5 mg three times a day in the first week and continued with 10 mg in the morning, 5 mg in the afternoon, and 5 mg in the evening during the second, third, and fourth weeks. The other group received diazepam 5 mg three times a day in all 4 weeks. On the evening of the seventh day of each treatment week the Hamilton Rating Scale for Anxiety and the Symptom Check List (90 items) were applied to assess the therapeutic effects, followed by an on-the-road driving test that started 1.5 hours after the last drug or placebo intake. The test consisted of operating an instrumented vehicle over a 100 kilometer highway circuit while attempting to maintain a constant speed and a steady lateral position within the right traffic lane. Two patients in the diazepam group were unable to complete their test after the first and second treatment week, respectively, because of serious sedative reactions. Both buspirone and diazepam were equally effective in reducing overall anxiety symptoms. The specific profiles showed that buspirone also reduced concomitant depressive symptoms and symptoms of interpersonal sensitivity and anger-hostility. In contrast, diazepam was found to be slightly more effective in reducing somatic symptoms and to positively affect sleep disturbances. Moreover, abrupt discontinuation of diazepam resulted in a relapse of psychic anxiety symptoms comparable with the placebo-baseline level and a partial relapse of somatic anxiety symptoms. Chronic treatment with buspirone had no significant effects on lateral position and speed control. In contrast, diazepam significantly impaired control of lateral position in the first 3 weeks of treatment. There was no significant impairment in the fourth treatment week and the placebo-washout week. Speed control was significantly impaired only in the first week. The relevance of the trend toward decreasing performance impairment during chronic treatment remains to be established.
两组各有12名门诊患者(6名男性和6名女性)患有广泛性焦虑症,参与了本研究。每位患者在最初7天(基线期)接受单盲安慰剂治疗,随后是连续4周的双盲药物治疗期(活性期),最后再次进行7天的单盲安慰剂治疗(洗脱期)。一组在第一周每天服用3次5毫克丁螺环酮,在第二、第三和第四周继续早上服用10毫克、下午服用5毫克、晚上服用5毫克。另一组在所有4周内每天服用3次5毫克地西泮。在每个治疗周的第七天晚上,应用汉密尔顿焦虑评定量表和症状自评量表(90项)来评估治疗效果,然后在最后一次服药或服用安慰剂1.5小时后开始进行道路驾驶测试。测试包括在一条100公里的高速公路线路上驾驶一辆装有仪器的车辆,同时试图保持恒定速度并在右侧行车道内保持稳定的横向位置。地西泮组分别有两名患者在第一和第二治疗周后因严重的镇静反应而无法完成测试。丁螺环酮和地西泮在减轻总体焦虑症状方面同样有效。具体情况表明,丁螺环酮还能减轻伴随的抑郁症状以及人际敏感和愤怒敌意症状。相比之下,发现地西泮在减轻躯体症状和积极影响睡眠障碍方面略更有效。此外,突然停用 地西泮会导致精神焦虑症状复发至与安慰剂基线水平相当的程度,以及躯体焦虑症状部分复发。长期服用丁螺环酮对横向位置和速度控制没有显著影响。相比之下,地西泮在治疗的前三周显著损害了横向位置控制。在第四治疗周和安慰剂洗脱周没有显著损害。速度控制仅在第一周受到显著损害。长期治疗期间性能损害减少趋势的相关性仍有待确定。