Rickels K, DeMartinis N, García-España F, Greenblatt D J, Mandos L A, Rynn M
Department of Psychiatry, University of Pennsylvania, Philadelphia, USA.
Am J Psychiatry. 2000 Dec;157(12):1973-9. doi: 10.1176/appi.ajp.157.12.1973.
Patients with generalized anxiety disorder (N=107) who had been long-term benzodiazepine users (average duration of use=8.5 years) were enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine (180 mg/day) and buspirone (38 mg/day) compared to placebo in facilitating benzodiazepine discontinuation.
After a benzodiazepine stabilization period taking either diazepam, lorazepam, or alprazolam, patients were treated for 4 weeks with imipramine, buspirone, or placebo under double-blind conditions while benzodiazepine intake was kept stable (treatment phase). Patients then entered a 4-6 week benzodiazepine taper and a 5-week posttaper phase with imipramine, buspirone, and placebo treatment being continued until 3 weeks into the posttaper phase, at which time all patients were switched to placebo for 2 weeks. Benzodiazepine plasma levels were assayed weekly. Benzodiazepine-free status was assessed 3 and 12 months posttaper.
Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts. The success rate of the taper in this study was significantly higher for patients who received imipramine (82.6%), and nonsignificantly higher for patients who received buspirone (67.9%), than for patients who received placebo (37.5%). The imipramine effect remained highly significant even after the analysis adjusted for three other independent predictors of taper success: benzodiazepine dose, level of anxious symptoms at baseline, and duration of benzodiazepine therapy.
Management of benzodiazepine discontinuation can be facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper. Daily benzodiazepine dose, severity of baseline symptoms of anxiety and depression, and duration of benzodiazepine use were additional significant predictors of successful taper outcome.
招募长期使用苯二氮䓬类药物（平均使用时长 = 8.5年）的广泛性焦虑症患者（N = 107名）参与一项苯二氮䓬类药物停药计划，该计划评估了在促进苯二氮䓬类药物停药方面，与安慰剂相比，联合使用丙咪嗪（180毫克/天）和丁螺环酮（38毫克/天）的有效性。
在服用地西泮、劳拉西泮或阿普唑仑的苯二氮䓬类药物稳定期后，患者在双盲条件下接受丙咪嗪、丁螺环酮或安慰剂治疗4周，同时保持苯二氮䓬类药物摄入量稳定（治疗阶段）。然后患者进入为期4 - 6周的苯二氮䓬类药物减量期和为期5周的减量后阶段，继续使用丙咪嗪、丁螺环酮和安慰剂治疗，直到减量后阶段的第3周，此时所有患者改用安慰剂治疗2周。每周检测苯二氮䓬类药物的血浆水平。在减量后3个月和12个月评估无苯二氮䓬类药物状态。
研究对象为长期使用苯二氮䓬类药物的患者，平均之前有三次减量尝试未成功。在本研究中，接受丙咪嗪治疗的患者减量成功率显著更高（82.6%），接受丁螺环酮治疗的患者减量成功率略高于接受安慰剂治疗的患者（67.9%对37.5%）。即使在对减量成功的其他三个独立预测因素进行分析调整后（苯二氮䓬类药物剂量、基线焦虑症状水平和苯二氮䓬类药物治疗时长），丙咪嗪的效果仍然非常显著。
在苯二氮䓬类药物减量前和减量期间联合使用丙咪嗪可显著促进苯二氮䓬类药物的停药管理。苯二氮䓬类药物的每日剂量、基线焦虑和抑郁症状的严重程度以及苯二氮䓬类药物的使用时长是减量成功结果的其他重要预测因素。
