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

Background: Over recent years, the use of antidepressants for the symptomat ic treatment of insomnia has grown substantially, but controlled studies ar e still lacking. Our study is the first investigation to prove objective ef ficacy and tolerability of low doses of a sedating antidepressant in a rand omized, double-blind, and placebo-controlled manner in patients with primar y 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 w eeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polys omnography at baseline and the first night of application, at 4 weeks of tr eatment and the first to third night of withdrawal, and after 2 weeks of wi thdrawal. Results: In the doxepin-treated patients who completed the study (N = 20, 4 7.6 +/- 11.3), medication significantly increased sleep efficiency after ac ute (night 1, p less than or equal to .001) and subchronic (night 28, p les s than or equal to .05) intake compared with the patients who received plac ebo (N = 20, 47.4 +/- 16.8 years of age). Latency to sleep onset was not af fected since the patients had normal baseline sleep latencies. Investigator s found doxepin to cause significantly (P less than or equal to .05) better global improvement at the first day of treatment. Patients rated sleep qua lity (p less than or equal to .001) and working ability (p less than or equ al to .005) to be significantly improved by doxepin during the whole treatm ent period. Overall rebound in sleep parameters was not observed, but patie nts with severe rebound insomnia were significantly more frequent in the do xepin group (night 29, p less than or equal to .01; night 30, p less than o r equal to .01; night 31, p less than or equal to .05). No significant grou p differences in side effects were Found, but 2 doxepin-treated patients dr opped out of the study due to specific side effects (increased liver enzyme s, leukopenia, and thrombopenia). Conclusion: The results support the effectiveness of low doses of doxepin t o improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound i nsomnia and specific side effects have to be considered.