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

INTRODUCTION: The efficacy and safety of doxepin (DXP) 6mg 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 6mg (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 6mg demonstrated statistically significant improvements in LPS (13min decrease versus PBO; p<0.0001), WASO (39min less than PBO; p<0.0001), TST (51min 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 8h (p⩽0.0003), all versus PBO. Additionally, DXP 6mg 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 6mg 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 6mg may be effective and well tolerated in adults experiencing transient insomnia.