title: Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.
abstract: 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 3 mg (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 (HAMD-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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. krystal@phy.duke.edu
authors.forename: Andrew
authors.initials: A
authors.lastname: Krystal
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Robert
authors.initials: R
authors.lastname: Rubens
authors.forename: Thomas
authors.initials: T
authors.lastname: Wessel
authors.forename: Judy
authors.initials: J
authors.lastname: Caron
authors.forename: Phebe
authors.initials: P
authors.lastname: Wilson
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: W Vaughn
authors.initials: WV
authors.lastname: McCall
mesh_terms: D000328:Adult; D053961:Azabicyclo Compounds; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D013997:Time Factors; D028761:Withholding Treatment / Q000706:statistics & numerical data*
chemical_list: D053961:Azabicyclo Compounds; D005473:Fluoxetine; D006993:Hypnotics and Sedatives; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; C515050:zopiclone