Sleep architecture and cognitive changes in olanzapine-treated patients with
depression: a double blind randomized placebo controlled trial.
Author(s): Lazowski LK, Townsend B, Hawken ER, Jokic R, du Toit R, Milev R(1).
Affiliation(s): Author information:
(1)Department of Psychiatry, Queen's University, 752 King Street West, Kingston, ON
K7L 4X3, Canada. roumen.milev@queensu.ca.
Publication date & source: 2014, BMC Psychiatry. , 14:202
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.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT00520507.
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