Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia.
OBJECTIVE
To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients.


METHODS
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.


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.
Roth
Thomas
T
Henri Ford Hospital, Detroit, MI 48202, USA. troth1@hfhs.org
Rogowski
Roberta
R
Hull
Steven
S
Schwartz
Howard
H
Koshorek
Gail
G
Corser
Bruce
B
Seiden
David
D
Lankford
Alan
A
D000293:Adolescent; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004316:Doxepin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D011446:Prospective Studies; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy*; D012895:Sleep, REM
D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin