Rickels K, DeMartinis N, Aufdembrinke B
Department of Psychiatry, University of Pennsylvania, University Science Center, Philadelphia 19104-2649, USA.
J Clin Psychopharmacol. 2000 Feb;20(1):12-8. doi: 10.1097/00004714-200002000-00004.
In a multicenter, double-blind trial, 310 patients who had received a diagnosis of generalized anxiety disorder were treated for 6 weeks with either abecarnil, diazepam, or placebo at mean daily doses of 12 mg of abecarnil or 22 mg of diazepam administered three times daily. Patients who were improved at 6 weeks could volunteer to continue double-blind treatment for a total of 24 weeks. The maintenance treatment phase allowed the comparison of taper results for the three treatments at several study periods (0-6 weeks, 7-12 weeks, and more than 12 weeks). Slightly more diazepam (77%) and placebo (75%) patients completed the 6-week study than abecarnil patients (66%). At intake and baseline, after a 1-week placebo washout, the patient was required to have a Hamilton Rating Scale for Anxiety score of > or =20. Major adverse events for both abecarnil and diazepam were drowsiness, dizziness, fatigue, and coordination difficulties. Clinical improvement data showed that both abecarnil and diazepam produced statistically significantly more symptom relief than did placebo after 1 week of treatment. At 6 weeks treatment (using last observation carried forward analysis), however, only diazepam still differed significantly (p < 0.01) from placebo. High placebo response (56% moderate to marked global improvement) at 6 weeks, as well as a slightly lower nonsignificant improvement rate observed with abecarnil, a partial y-aminobutyric acid (GABA) agonist, when compared with diazepam, a full GABA agonist, most likely contributed to our findings. Finally, taper results showed that only diazepam and not abecarnil caused the presence of temporary discontinuation symptoms, but only in patients who had been treated for at least 12 weeks.
在一项多中心双盲试验中，310名被诊断为广泛性焦虑症的患者接受了为期6周的治疗，分别服用阿贝卡尼、地西泮或安慰剂，阿贝卡尼的平均日剂量为12毫克，地西泮为22毫克，均每日服用三次。6周时病情有所改善的患者可自愿继续接受双盲治疗，为期共24周。维持治疗阶段可在几个研究时间段（0至6周、7至12周以及超过12周）比较三种治疗的撤药结果。完成6周研究的地西泮患者（77%）和安慰剂患者（75%）略多于阿贝卡尼患者（66%）。在入组时和基线时，经过1周的安慰剂洗脱期后，要求患者的汉密尔顿焦虑量表评分≥20分。阿贝卡尼和地西泮的主要不良事件均为嗜睡、头晕、疲劳和协调困难。临床改善数据显示，治疗1周后，阿贝卡尼和地西泮在统计学上比安慰剂产生的症状缓解明显更多。然而，在6周治疗时（采用末次观察结转分析），只有地西泮与安慰剂仍有显著差异（p<0.01）。6周时安慰剂反应率较高（56%为中度至显著的整体改善），以及与完全γ-氨基丁酸（GABA）激动剂地西泮相比，部分GABA激动剂阿贝卡尼观察到的改善率略低且无统计学意义，很可能是导致我们研究结果的原因。最后，撤药结果显示，只有地西泮而非阿贝卡尼会导致出现暂时停药症状，但仅在接受治疗至少12周的患者中出现。
