Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in elderly patients with primary insomnia: a randomized, double-blind, placebo-controlled crossover study.

Objectives: Evaluate efficacy and safety of the histamine-H 1 antagonist doxepin at doses of 1 mg, 3 mg, and 6 mg in elderly adults with primary insomnia. Design: A randomized, double-blind, placebo-controlled, crossover design was used in this population of elderly adults with primary insomnia (DSM-IV). Each treatment period consisted of 2 poly-somnographic (PSG) assessment nights with a 5- or 12-day drug-free interval between periods. The study was conducted from September 2004 to January 2005. Setting: Sleep laboratories in 11 sleep centers in the United States. Participants: Elderly adults with primary insomnia. Intervention: Doxepin 1 mg, 3 mg, and 6 mg. Measurements: Efficacy was assessed using PSG and patient-reported measures. Results: Seventy-six patients were randomly assigned. All 3 doxepin doses produced dose-related significant improvements in PSG-determined wake time during sleep (p <.0001), wake time after sleep onset (p <.0001), total sleep time (p <.0001), and overall sleep efficiency (p <.0001) versus placebo. At the 3-mg and 6-mg doses, sleep efficiency was significantly improved during all thirds of the night (p <.05). There was a dose-related decrease in patient-reported sleep latency, with the 6-mg dose achieving statistical significance in latency to sleep onset (p =.0181). The pattern of the remaining subjective efficacy results was consistent with PSG. All 3 doxepin doses had side effect profiles comparable to placebo, with no spontaneously reported anticholinergic effects, no memory impairment, and no significant next-day residual effects. Conclusions: In this 2-night study of elderly adults with primary insomnia, doxepin doses of 1 mg, 3 mg, and 6 mg were well tolerated and produced significant improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. Positive effects on patient-reported sleep onset were observed at the highest dose. All 3 doxepin doses had a safety profile comparable to placebo. These data demonstrate that doxepin was efficacious in improving sleep in elderly adults.