小剂量多塞平治疗伴发焦虑症共病性失眠的临床疗效与安全性研究

Study of the Clinical Effect and Safety of the Low-Dose Doxepin in the Treatment of Comorbid Insomnia Patients with Anxiety Disorders

摘要: 目的：对比分析小剂量多塞平治疗伴发焦虑症的共病性失眠患者的有效剂量、疗效差异及临床安全性。方法：采用病例随机对照研究方法，将78例伴发焦虑症的共病性失眠患者随机分成2组，分别为西酞普兰组(39例)和多塞平组(39例)，两组病例每日分别服用西酞普兰(20 mg/d)和多塞平(6.25~12.5 mg/d)，治疗持续12周。两组病例的睡眠状况的变化用匹兹堡睡眠量表(PSQI)来评定，该量表包括睡眠质量、睡眠时间、睡眠效率、睡眠障碍和日间功能障碍6个因子项。在治疗后4周、8周与12周时间点上，对病例根据PSQI和汉密尔顿焦虑量表(HAMA)进行评定，并收集数据并观察记录治疗的安全性。结果：与治疗前相比，在治疗后4周、8周与12周时间点上我们发现：① 在治疗后3个时间点，小剂量多塞平组的PSQI总分及因6个因子项评分均明显下降(P < 0.05)，研究结果提示小剂量多塞平可以明显改善睡眠质量；② 伴随着睡眠质量的改善，2组患者的焦虑症状也获得了明显缓解(P < 0.05)；与西酞普兰组比较发现，多塞平组在治疗后8周(P < 0.01)与12周(P < 0.001)时，入睡时间缩短，主观睡眠质量改善。两组之间的不良反应差异无统计学意义(P = 0.404)。结论：小剂多塞平适合于伴发焦虑症共病性失眠的长期治疗。但多塞平可能更加适用于入睡困难明显的共病性失眠患者。

Abstract: Objective: To analyze the suited dose, the different efficacy, and clinical safety of low-dose doxepin (DXP) in anxiety patient with insomnia disorders. Methods: The study was a randomized paral-lel-group trial. 78 cases of comorbid insomnia patients with anxiety disorders were randomly di-vided into two groups, namely citalopram group (39 cases) and DXP group (39 cases). Two treat-ment groups were treated respectively with citalopram (20 mg/d) or DXP (6.25 - 12.5 mg/d) and treatment lasts 12 weeks. The sleep quality was assessed with Pittsburgh sleep quality index (PSQI), which could be divided into 6 factors, including subjective sleep quality, sleep duration, habitual sleep efficiency, sleep disturbance, and daytime dysfunction. At three treatment time-points of 4, 8 and 12 weekends, patients completed two structured questionnaires: Pttsburgh Sleep Quality Index (PSQI) and Hamilton Anxiety Scale (HAMA), and data were collected. Safety assessments were conducted throughout the study. Results: 1) At three treatment time-points of 4, 8 and 12 weekends, we found that PSQI scores and the 6 factor scores of PSQI are obviously lowered in Citalopram and DXP groups (P < 0.05). Our outcomes suggested that DXP significantly improved total sleep quality. 2) With obviously overall improvement in sleep quality, the anxiety of the teo groups also significantly improved (P < 0.05). However, DXP group had a shorter sleep onset latency (SOL) and improved subjective sleep quality than citalopram group at time-points of the 8th weekend (P < 0.01) and 12th weekend (P < 0.001). And there was no statistically significant difference in adverse events of the two groups (P = 0.404). Conclusion: Based on our outcomes, we concluded low-dose DXP could be used for long-term treatment of the co-morbid insomnia patients with anxiety disorders. Furthermore, low-dose DXP appears to be more suitable for the treatment of co-morbid insomnia patients with anxiety disorders, especially difficulties initiating sleep as the main performance.