Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia

作者：Andrew D. Krystal, Alan Lankford, H. Heith Durrence, Elizabeth Ludington, Philip Jochelson, Roberta Rogowski, Thomas Röth · 发表于：SLEEP · 年份：2011 · DOI：10.5665/sleep.1294 · 被引用次数：129 · 研究领域：Sleep and related disorders、Sleep and Wakefulness Research、Sleep and Work-Related Fatigue

STUDY OBJECTIVES: To evaluate the efficacy and safety of doxepin (DXP) 3 mg and 6 mg in adults diagnosed with primary insomnia. DESIGN AND METHODS: The study was a randomized, double-blind, parallel-group, placebo-controlled trial. Patients meeting DSM-IV-TR criteria for primary insomnia were randomized to 35 days of nightly treatment with DXP 3 mg (n=75), DXP 6 mg (n=73), or placebo (PBO; n=73), followed by 2 nights of single-blind PBO to evaluate discontinuation (DC) effects. Efficacy was assessed using polysomnography (PSG) and patient reports. Efficacy data were examined for Night (N) 1, N15, and N29. Safety assessments were conducted throughout the study. RESULTS: Compared with PBO, DXP 3 and 6 mg significantly improved wake time after sleep onset (WASO) on N1 (3 mg and 6 mg; P<0.0001), N15 (3 mg P=0.0025; 6 mg P=0.0009), and N29 (3 mg P=0.0248; 6 mg P=0.0009), latency to persistent sleep (LPS) on N1 (3 mg P=0.0047; 6 mg P=0.0007), and total sleep time (TST) on N1 (3 mg and 6 mg P<0.0001), N15 (6 mg P=0.0035), and N29 (3 mg P=0.0261; 6 mg P<0.0001). In terms of early morning awakenings, DXP 3 and 6 mg demonstrated significant improvements in SE in the final quarter of the night on N1, N15, and N29, with the exception of 3 mg on N29 (P=0.0691). Rates of discontinuation were low, and the safety profiles were comparable across the 3 treatment groups. There were no significant next-day residual effects, and there were no spontaneous reports of memory impairment, complex slee...