Use of ultra-low-dose (≤6 mg) doxepin for treatment of insomnia in older people

Abstract

Background: Insomnia is one of the most frequent complaints encountered in primary care practice, one that results in significant clinical consequences and cost burden to the public health system. It is more common in elderly adults (≥65 years of age), with frequent complaints regarding sleep maintenance and early morning wakening. Current treatment options have limitations. This review was conducted to evaluate the evidence behind ultra-low-dose doxepin in insomnia and to discuss its potential advantages, its place in therapy and its implications in practice in the treatment of older patients. Methods: A systematic literature search was conducted of MEDLINE via Ovid, PubMed and EMBASE using the MeSH and key terms “doxepin,” “sleep initiation and maintenance disorders,” “insomnia,” and “low dose.” Only randomized controlled trials comparing 3 mg and/or 6 mg of doxepin to placebo and involving participants diagnosed with primary insomnia were included. Primary outcomes for this review were objective sleep study parameters. Results: Five studies were identified, 3 of which ( n = 571) were conducted in older adults. Doxepin 3 mg and 6 mg significantly reduced waking after sleep onset and increased total sleep time. There was no significant difference between the 2 doses of doxepin. Latency to persistent sleep did not differ significantly compared with placebo for any doses of doxepin. The most frequent adverse events reported were somnolence and headache. Adverse events did not appear to be dose-related, and studies reported the incidence of adverse effects to be comparable to placebo. Conclusion: Doxepin 3 mg and 6 mg significantly improved and sustained sleep maintenance and sleep duration into the last third of the night but did not significantly affect sleep onset. Sleep benefits were achieved without next-day residual or discontinuation effects. Doxepin appears to be well suited for managing insomnia in older people.