摘要： 目的 探讨曲唑酮对苯二氮卓类药物依赖性失眠的疗效和安全性。方法 共40 例苯二氮卓类药物依赖性失眠患者，分为苯二氮卓类联合曲唑酮组（曲唑酮组）和苯二氮卓类联合安慰剂组（对照组），逐渐减半苯二氮卓类药物剂量，治疗3 个月后根据Holtzman-Gellert戒断症状评分法、汉密尔顿焦虑量表（HAMA）和多导睡眠图监测结果评价曲唑酮戒断疗效，副反应量表（TESS）评价药物不良反应。结果 与对照组比较，曲唑酮组患者自治疗后7 d 戒断症状评分开始降低（P = 0.000），自治疗后15 d HAMA 评分开始降低（P = 0.000）；与治疗前比较，经曲唑酮治疗后两项评分均降低（P = 0.000）。与对照组比较，曲唑酮组患者治疗后7 d 总睡眠时间和慢波睡眠时间延长、睡眠效率提高、睡眠潜伏期缩短（均P = 0.000）；与治疗前相比，经曲唑酮治疗后总睡眠时间和慢波睡眠时间延长、睡眠效率提高、睡眠潜伏期缩短（均P = 0.000）。未见明显不良反应，两组患者治疗前后TESS 评分差异无统计学意义（P > 0.05）。结论 曲唑酮治疗苯二氮卓类药物依赖和戒断反应疗效显著，且安全性良好。

关键词: 曲唑酮, 苯二氮卓类, 物质戒断综合征, 焦虑, 睡眠障碍, 随机对照试验

Abstract: Objective To determine the efficacy and safety of trazodone in the treatment of benzodiazepine dependence. Methods  Forty insomnia patients who met the Classification and Diagnostic Criteria of Mental Disorders in China Third Edition (CCMD-3) of dependence syndrome due to benzodiazepine were involved in the study. Patients were randomly assigned to trazodone group and placebo group for 3 months. The efficacy were assessed by Withdrawal Symptoms Checklist, Hamilton Anxiety Rating Scale (HAMA) and polysomnography (PSG). Adverse events were assessed by Treatment Emergent Symptom Scale (TESS). Results  The Withdrawal Symptoms Checklist of trazodone group was significantly lower after 7 d treatment than that of placebo group (P = 0.000), and HAMA score of the trazodone group was also significantly lower after 15 d treatment than that of placebo group (P = 0.000). There were no difference in Withdrawal Symptoms Checklist and HAMA of placebo group before and after treatment. Withdrawal Symptoms Checklist and HAMA of the trazodone group were decreased after treatment (P = 0.000). In comparison with placebo group, sleep parameters of the trazodone, including total sleep time (TST), sleep efficiency (SE), sleep latency (SL) and slow wave sleep (SWS) time presented improvement after 7 d treatment (P = 0.000, for all). After trazodone treatment, total sleep time, slow wave sleep time, sleep efficiency and sleep latency were improved (P = 0.000, for all). No obvious adverse reaction occurred. There were no significant differences in TESS scores between pre? and post?treatment in both groups (P > 0.05). Conclusion  Trazodone is markedly effective and safe in the treatment for benzodiazepine dependence.

Key words: Trazodone, Benzodiazepines, Substance withdrawal syndrome, Anxiety, Sleep disorders, Randomized controlled trial