title: The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized placebo-controlled trial.
abstract: OBJECTIVE
  In schizophrenia there is a dramatic reduction of sleep spindles that predicts deficient sleep-dependent memory consolidation. Eszopiclone (Lunesta), a non-benzodiazepine hypnotic, acts on γ-aminobutyric acid (GABA) neurons in the thalamic reticular nucleus where spindles are generated. We investigated whether eszopiclone could increase spindles and thereby improve memory consolidation in schizophrenia.
  
  
  METHODS
  In a double-blind design, patients were randomly assigned to receive either placebo or 3 mg of eszopiclone. Patients completed Baseline and Treatment visits, each consisting of two consecutive nights of polysomnography. On the second night of each visit, patients were trained on the motor sequence task (MST) at bedtime and tested the following morning.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Twenty-one chronic, medicated schizophrenia outpatients.
  
  
  RESULTS
  We compared the effects of two nights of eszopiclone vs. placebo on stage 2 sleep spindles and overnight changes in MST performance. Eszopiclone increased the number and density of spindles over baseline levels significantly more than placebo, but did not significantly enhance overnight MST improvement. In the combined eszopiclone and placebo groups, spindle number and density predicted overnight MST improvement.
  
  
  CONCLUSIONS
  Eszopiclone significantly increased sleep spindles, which correlated with overnight motor sequence task improvement. These findings provide partial support for the hypothesis that the spindle deficit in schizophrenia impairs sleep-dependent memory consolidation and may be ameliorated by eszopiclone. Larger samples may be needed to detect a significant effect on memory. Given the general role of sleep spindles in cognition, they offer a promising novel potential target for treating cognitive deficits in schizophrenia.
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Wamsley
authors.forename: Ann K
authors.initials: AK
authors.lastname: Shinn
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Kim E
authors.initials: KE
authors.lastname: Ono
authors.forename: Sophia K
authors.initials: SK
authors.lastname: McKinley
authors.forename: Alice V
authors.initials: AV
authors.lastname: Ely
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.forename: Robert
authors.initials: R
authors.lastname: Stickgold
authors.forename: Dara S
authors.initials: DS
authors.lastname: Manoach
mesh_terms: D000328:Adult; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D004569:Electroencephalography; D000069582:Eszopiclone; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009483:Neuropsychological Tests; D010879:Piperazines / Q000494:pharmacology*; D017286:Polysomnography; D012559:Schizophrenia / Q000503:physiopathology*; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D000069582:Eszopiclone
keywords: Schizophrenia; automation; memory consolidation; motor skill; procedural learning; sleep spindles