Efficacy and safety of doxepin 6 mg in a four-week outpatient trial of elderly adults with chronic primary insomnia

Sleep Med. 2012 Feb;13(2):133-8. doi: 10.1016/j.sleep.2011.09.006. Epub 2011 Dec 24.


Introduction: The efficacy and safety of doxepin (DXP), a histamine H(1) receptor antagonist, was evaluated in elderly adults with sleep maintenance insomnia.

Methods: This was a randomized, double-blind, placebo-controlled outpatient trial. Elderly adults meeting DSM-IV-TR criteria for primary insomnia were randomized to four weeks of nightly treatment with either DXP 6 mg (N=130) or placebo (PBO; N=124). Efficacy was assessed using patient self-report instruments and clinician ratings. Patient-reported endpoints included subjective total sleep time (sTST), subjective wake after sleep onset (sWASO), latency to sleep onset (LSO), sleep quality, and a Patient Global Impression scale (PGI). The primary endpoint was sTST at week 1.

Results: DXP 6 mg produced significantly more sTST and less sWASO at week 1 (both p-values <0.0001) than PBO. These significant improvements versus placebo were maintained at weeks 2-4 (all p-values <0.05). There were no significant differences in LSO for DXP 6 mg versus PBO. DXP 6 mg significantly improved sleep quality (weeks 1, 3, and 4, p<0.05) and several outcome-related parameters, including several items on the PGI, the severity and improvement items of the Clinician Global Impression scale (CGI; weeks 1 and 2) and the Insomnia Severity Index (ISI; weeks 1-4), all versus PBO. There were no reports of anticholinergic effects (e.g., dry mouth) or memory impairment. The safety profile of DXP 6 mg was comparable to that of PBO.

Conclusions: In elderly adults with insomnia, DXP 6 mg produced significant improvements in sleep maintenance, sleep duration, and sleep quality endpoints that were sustained throughout the trial. These data suggest that DXP 6 mg is effective for treating sleep maintenance insomnia and is well-tolerated in elderly adults with chronic primary insomnia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Doxepin / administration & dosage*
  • Doxepin / adverse effects
  • Female
  • Histamine H1 Antagonists / administration & dosage*
  • Histamine H1 Antagonists / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Outpatients
  • Placebos
  • Sleep / drug effects*
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Treatment Outcome


  • Histamine H1 Antagonists
  • Placebos
  • Doxepin