Doxepin in the treatment of primary insomnia:: A placebo-controlled, double-blind, polysomnographic study

Background: Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. Method: Forty seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2 +/- 9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. Results: In the doxepin-treated patients who completed the study (N = 20, 47.6 +/- 11.3), medication significantly increased sleep efficiency after acute (night 1, p less than or equal to .001) and subchronic (night 28, p less than or equal to .05) intake compared with the patients who received placebo (N = 20, 47.4 +/- 16.8 years of age). Latency to sleep onset was not affected since the patients had normal baseline sleep latencies. Investigators found doxepin to cause significantly (P less than or equal to .05) better global improvement at the first day of treatment. Patients rated sleep quality (p less than or equal to .001) and working ability (p less than or equal to .005) to be significantly improved by doxepin during the whole treatment period. Overall rebound in sleep parameters was not observed, but patients with severe rebound insomnia were significantly more frequent in the doxepin group (night 29, p less than or equal to .01; night 30, p less than or equal to .01; night 31, p less than or equal to .05). No significant group differences in side effects were Found, but 2 doxepin-treated patients dropped out of the study due to specific side effects (increased liver enzymes, leukopenia, and thrombopenia). Conclusion: The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.