OBJECTIVES: Evaluate efficacy and safety of the histamine-H1 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 polysomnographic (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. Copyright 2008 Physicians Postgraduate Press, Inc.
RCT Entities:
OBJECTIVES: Evaluate efficacy and safety of the histamine-H1 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 polysomnographic (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 3doxepin 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 3doxepin 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 3doxepin doses had a safety profile comparable to placebo. These data demonstrate that doxepin was efficacious in improving sleep in elderly adults. Copyright 2008 Physicians Postgraduate Press, Inc.
Authors: Andrew D Krystal; Alan Lankford; H Heith Durrence; Elizabeth Ludington; Philip Jochelson; Roberta Rogowski; Thomas Roth Journal: Sleep Date: 2011-10-01 Impact factor: 5.849