title: Sleep architecture and cognitive changes in olanzapine-treated patients with depression: a double blind randomized placebo controlled trial.
abstract: BACKGROUND
  Disturbance in sleep quality is a symptom of Major Depressive Disorder (MDD) and Bipolar Disorder (BD) and thus improving quality of sleep is an important aspect of successful treatment. Here, a prospective, double-blind, randomized, placebo-controlled study examined the effect of olanzapine (an atypical antipsychotic) augmentation therapy on sleep architecture, specifically slow wave sleep (SWS), in the treatment of depression. The effect of olanzapine augmentation therapy on other features of sleep (e.g., sleep continuity) and depression (e.g., illness severity and cognitive function) were also determined.
  
  
  METHODS
  Patients currently experiencing a major depressive episode and who were on a stable medication were included. Sleep architecture was measured by overnight ambulatory polysomnography. Illness severity was determined using the Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive function was examined using Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Working Memory (SWM), Spatial Span (SSP), and Reaction Time (RTI) tasks. Polysomnographs, clinical measures and cognitive tests were administered at baseline, after 2-4 days of treatment and after 28-31 days of treatment. Twenty-five patients participated in the study (N = 10, N = 15 for placebo and olanzapine treated groups respectively).
  
  
  RESULTS
  The primary objective of the study was to assess the objective (polysomnographic) changes in sleep quality, defined as changes in SWS, following olanzapine treatment for depression. Latency to but not duration of SWS was found to significantly differ between olanzapine- and placebo-treated participants (Hedge's g: 0.97, 0.13 respectively). A significant improvement in olanzapine-treated participants over placebo-treated participants was observed in secondary outcome measures, including sleep efficiency, total sleep time, and sleep latency. Secondary objectives assessed the subjective changes in sleep quality parameters and correlated them with measures of illness severity and changes in cognition. MADRS scores were significantly improved in olanzapine-treated participants over time but not more than placebo treatment. There was no significant difference between olanzapine- and placebo-treated participants in SWM, SSP or RTI tasks.
  
  
  CONCLUSIONS
  Olanzapine augmentation treatment generally did not improve SWS but did improve sleep continuity and depression. Olanzapine may be one of few medications that improve sleep continuity, thus directly targeting symptoms of depression.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT00520507.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Lazowski
authors.forename: Ben
authors.initials: B
authors.lastname: Townsend
authors.forename: Emily R
authors.initials: ER
authors.lastname: Hawken
authors.forename: Ruzica
authors.initials: R
authors.lastname: Jokic
authors.forename: Regina
authors.initials: R
authors.lastname: du Toit
authors.affiliation: Department of Psychiatry, Queen's University, 752 King Street West, Kingston, ON K7L 4X3, Canada. roumen.milev@queensu.ca.
authors.forename: Roumen
authors.initials: R
authors.lastname: Milev
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011446:Prospective Studies; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D011795:Surveys and Questionnaires
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine