Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression

Andrew Krystal, Maurizio Fava, Robert Rubens, Thomas Wessel, Judy Caron, Phebe Wilson, Thomas Roth, William Vaughn McCall

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Background: Insomnia and major depressive disorder (MDD) may coexist. This study evaluated hypnotic discontinuation effects following an 8-week placebo-controlled study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid MDD. Methods: Patients meeting DSM-IV criteria for MDD and insomnia received fluoxetine each morning for 8 weeks and were randomized to concomitant treatment with nightly eszopiclone 3mg (cotherapy) or placebo (monotherapy). Thereafter, patients received 2 weeks of continued fluoxetine plus single-blind placebo. Results: Incidence rates of central nervous system (CNS) and potentially CNS-related adverse events (AEs) during the run-out period were similar between treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global Impression improvements in depressive symptoms were maintained after eszopiclone discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAM-D-17) scores with cotherapy versus monotherapy seen at Week 8 (p= .0004) were maintained at Week 10 (p< .0001) and significantly higher depression response and remission rates were observed after cotherapy at Week 10 (p< .02). Patients discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO (wake after sleep onset), and TST (total sleep time) during the 2 weeks following discontinuation (P< 05). Conclusions: In this study, eszopiclone discontinuation did not result in significant CNS or benzodiazepine withdrawal AEs, rebound insomnia, or rebound depression; and improvements in sleep and depressive symptoms were maintained.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalJournal of Clinical Sleep Medicine
Issue number1
StatePublished - Feb 15 2007


  • Eszopiclone
  • Fluoxetine
  • Insomnia
  • Major depressive disorder
  • Rebound
  • Withdrawal

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Neurology
  • Clinical Neurology


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