Low-dose doxepin improves wake after sleep onset among individuals with primary insomnia, data indicate
Wednesday, December 12 2007 | Comments
The investigational insomnia agent doxepin improves wake after sleep onset (WASO) in people with primary insomnia, according to study findings. Additional findings suggest the improvement in WASO observed after 1 night of treatment is sustained after >=1 month of treatment.
During the trial, adults who had primary insomnia for >=3 months were randomized to receive nightly treatment with placebo (n=73), doxepin 3 mg (n=75), or doxepin 6 mg (n=73).
Polysomnography (PSG) confirmed that all participants experienced >=60 minutes of WASO and had a total sleep time (TST) <=410 minutes but >240 minutes at baseline.
The primary endpoint of the trial was PSG-measured WASO during night 1 of treatment. Relative to placebo, doxepin 3 mg and 6 mg reduced mean WASO by approximately 30 minutes and 35 minutes, respectively (P<.0001 for both). Differences between doxepin and placebo remained significant at night 29 (3 mg, P=.0299; 6 mg, P=.0012).
Thomas Roth, a study investigator from the Henry Ford Sleep Disorders and Research Center
in Detroit, noted that both doses of doxepin also significantly improved TST and sleep efficiency at both time points as compared with placebo. Improvements in sleep efficiency among doxepin-treated participants relative to placebo-treated participants were generally observed during each hour of the night, he added.
Both doses of doxepin significantly improved latency to persistent sleep (LPS) during night 1 as compared with placebo (3 mg, P=.011; 6 mg, P=.0018), but differences between doxepin and placebo were not significant at night 29. However, the study researchers explained, the lack of statistical significance might be due primarily to improvement in LPS among placebo-treated participants. Roth also noted that participants in the current study did not necessarily have difficulties with sleep onset at baseline.
According to Roth, in subjective assessments of efficacy, doxepin was associated with improvements in WASO and TST at night 1, but not at night 29. There were no significant differences between doxepin and placebo in subjective assessments of sleep-onset latency at either time point.
In addition, there were no significant differences between doxepin and placebo in next-day assessments of residual sedation, which included the Digit Symbol Substitution Test, the Symbol Copying Task, and a visual analog scale of alertness.
The incidence of adverse events was comparable between doxepin and placebo, and there were no reports of amnesia or anticholinergic effects, according to the study investigators. The most common adverse events were somnolence and nausea. (Lankford A, et al. Poster #0750.)
This information concerns a use that has not been approved by the Food and Drug Administration