Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia

Sleep. 2007 Nov;30(11):1555-61. doi: 10.1093/sleep/30.11.1555.


Study objectives: To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients.

Design: Adults (18-64 y) with chronic primary insomnia (DSM-IV) were randomly assigned to one of four sequences of 1 mg, 3 mg, and 6 mg of doxepin, and placebo in a crossover study. Treatment periods consisted of 2 polysomnographic assessment nights with a 5-day or 12-day drug-free interval between periods. Efficacy was assessed using polysomnography (PSG) and patient-reported measures. Safety analyses included measures of residual sedation and adverse events.

Measurements and results: Sixty-seven patients were randomized. Wake time during sleep, the a priori defined primary endpoint, was statistically significantly improved at the doxepin 3 mg and 6 mg doses versus placebo. All three doses had statistically significant improvements versus placebo for PSG-defined wake after sleep onset, total sleep time, and overall sleep efficiency (SE). SE in the final third-of-the-night also demonstrated statistically significant improvement at all doses. The doxepin 6 mg dose significantly reduced subjective latency to sleep onset. All three doxepin doses had a safety profile comparable to placebo. There were no statistically significant differences in next-day residual sedation, and sleep architecture was generally clinically preserved.

Conclusions: In adults with primary insomnia, doxepin 1 mg, 3 mg, and 6 mg was well-tolerated and produced improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. The side-effect profile was comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is efficacious in improving the sleep of patients with chronic primary insomnia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Chronic Disease
  • Cross-Over Studies
  • Double-Blind Method
  • Doxepin / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polysomnography
  • Prospective Studies
  • Sleep Initiation and Maintenance Disorders / diagnosis
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep, REM


  • Antidepressive Agents, Tricyclic
  • Doxepin