Efficacy and safety of doxepin 6 mg in a model of transient insomnia

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Introduction The efficacy and safety of doxepin (DXP) 6 mg tablets were evaluated in healthy adults in a model of transient insomnia. Methods This was a randomized, double-blind, parallel-group, placebo-controlled study in healthy adults using a model of transient insomnia. A first-night effect combined with a 3-h phase advance was implemented to induce transient insomnia in healthy adults. Subjects received a single night time dose of placebo (PBO; N = 282) or DXP 6 mg ( N = 283) in a sleep laboratory. Efficacy was evaluated objectively (polysomnography; PSG) and subjectively (morning questionnaire). Consistent with the model utilized, the primary endpoint was latency to persistent sleep (LPS); secondary PSG endpoints included wake after sleep onset (WASO; key secondary endpoint), total sleep time (TST), wake time after sleep (WTAS) and sleep efficiency (SE; overall, by quarter of the night and hourly); secondary subjective endpoints included latency to sleep onset (LSO), subjective WASO (sWASO), subjective TST (sTST) and sleep quality. Results DXP 6 mg demonstrated statistically significant improvements in LPS (13 min decrease versus PBO; p < 0.0001), WASO (39 min less than PBO; p < 0.0001), TST (51 min more than PBO; p < 0.0001), WTAS ( p < 0.0001), overall SE ( p < 0.0001), SE in each quarter of the night ( p < 0.0001) and SE in each of the 8 h ( p ⩽ 0.0003), all versus PBO. Additionally, DXP 6 mg significantly improved subjective variables including LSO ( p < 0.0001), sWASO ( p = 0.0063), sTST ( p < 0.0001), and sleep quality ( p = 0.0004), versus PBO. There was no consistent evidence of next-day residual sedation and also minor sleep stages alterations. The incidence of adverse events was comparable to placebo. Conclusions In this model of transient insomnia, DXP 6 mg demonstrated significant improvements in sleep onset, sleep maintenance, sleep duration and sleep quality, and also appeared to reduce early morning awakenings. These data suggest that DXP 6 mg may be effective and well tolerated in adults experiencing transient insomnia.