Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder

Biol Psychiatry. 2006 Jun 1;59(11):1052-60. doi: 10.1016/j.biopsych.2006.01.016. Epub 2006 Apr 3.


Background: Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding eszopiclone to fluoxetine.

Methods: Patients who met DSM-IV criteria for both MDD and insomnia (n = 545) received morning fluoxetine and were randomized to nightly eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S).

Results: Patients in the ESZ+FLX group had significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p < .05). Eszopiclone co-therapy also resulted in: significantly greater changes in HAM-D-17 scores at Week 4 (p = .01) with progressive improvement at Week 8 (p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 (p < .05); and significantly more responders (59% vs. 48%; p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates.

Conclusions: In this study, eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect.

Publication types

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

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Azabicyclo Compounds
  • Depressive Disorder / complications*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use*
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use
  • Male
  • Middle Aged
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Psychiatric Status Rating Scales
  • Self Disclosure
  • Severity of Illness Index
  • Sleep / drug effects
  • Sleep Initiation and Maintenance Disorders / complications*
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / psychology
  • Time Factors
  • Treatment Outcome


  • Antidepressive Agents, Second-Generation
  • Azabicyclo Compounds
  • Hypnotics and Sedatives
  • Piperazines
  • Fluoxetine
  • zopiclone