Effectiveness of cognitive behavioral therapy for pharmacotherapy-resistant chronic insomnia: a multi-center randomized controlled trial in Japan

Abstract

ObjectivesAn 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. MethodsThis 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. ResultsA 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. ConclusionAdd-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. Trial registrationUMIN Clinical Trials Registry identifier: UMIN000014297.