Department of Sleep-Wake Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8553, Japan.
Department of Psychological Counseling, Faculty of Humanities, Tokyo Kasei University, 1-18-1 Kaga, Itabashi-ku, Tokyo, 173-8602, Japan; Japan Somnology Center, Institute of Neuropsychiatry, 5-10-10 Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan.
Sleep Med. 2018 Oct;50:105-112. doi: 10.1016/j.sleep.2018.05.038. Epub 2018 Jun 18.
An insomnia characterized by nighttime symptoms and daytime impairment is common. GABA-A receptor agonist (GABAA-RA) treatment is often used, but long-term use is controversial due to the poor risk-benefit ratio resulting from drug dependence and potential cognitive impairment. This study evaluated the effectiveness of add-on cognitive behavioral therapy for insomnia (CBT-I) and GABAA-RA dose-tapering in patients with primary insomnia resistant to pharmacotherapy.
This randomized, multicenter, two-arm, parallel-group study compared CBT-I and treatment as usual (TAU) in patients with persistent primary insomnia despite GABAA-RA treatment. Screening was based on sleep diary entries, with ≥31-min sleep latency or wake after sleep onset, occurring ≥3 times in a week and total score of ≥8 on the Insomnia Severity Index (ISI). Primary outcome measures were severity of insomnia and GABAA-RA tapering rate.
A total of 51 patients were randomized and 49 patients were analyzed (CBT-I; n = 23, TAU; n = 26). A mixed-effects repeated-measures model revealed significant improvement in insomnia symptoms (ISI score) during the post-intervention (PI) and follow-up (FU) periods in the CBT-I versus the TAU group (PI; 10.91 vs. 14.33, p < 0.05, FU; 10.17 vs. 14.34, p < 0.01). GABAA-RA tapering rate approached 30% during follow-up in the CBT-I group; no significant intergroup difference was observed.
Add-on CBT-I improved insomnia symptoms that were unresponsive to GABAA-RA therapy. No effect on tapering rate was observed in this study. CBT-I may promote dose reduction by optimizing the protocol and duration of treatment.
UMIN Clinical Trials Registry identifier: UMIN000014297.
以夜间症状和日间损害为特征的失眠症较为常见。常使用 GABA-A 受体激动剂（GABAA-RA）治疗，但由于药物依赖和潜在认知障碍导致的风险效益比较差，长期使用存在争议。本研究评估了附加认知行为疗法治疗失眠症（CBT-I）和 GABA-A-RA 剂量逐渐减少对原发性失眠症患者的疗效，这些患者对药物治疗有耐药性。
这是一项随机、多中心、双臂、平行组研究，比较了原发性失眠症患者在接受 GABA-A-RA 治疗后仍持续存在的情况下，CBT-I 和常规治疗（TAU）的效果。筛查基于睡眠日记条目，每周至少出现 3 次、入睡后觉醒时间≥31 分钟或总得分≥8 的失眠严重程度指数（ISI）。主要观察指标为失眠严重程度和 GABA-A-RA 逐渐减少率。
共有 51 名患者被随机分组，49 名患者被纳入分析（CBT-I；n=23，TAU；n=26）。混合效应重复测量模型显示，CBT-I 组在干预后（PI）和随访（FU）期间的失眠症状（ISI 评分）有显著改善，而 TAU 组则无显著改善（PI：10.91 与 14.33，p<0.05，FU：10.17 与 14.34，p<0.01）。在 CBT-I 组，GABA-A-RA 逐渐减少率在随访期间接近 30%；但两组间无显著差异。
附加 CBT-I 改善了对 GABA-A-RA 治疗无反应的失眠症状。本研究未观察到对逐渐减少率的影响。CBT-I 可能通过优化治疗方案和持续时间来促进剂量减少。
UMIN 临床研究注册数据库注册号：UMIN000014297。
