Olanzapine Increases Slow Wave Sleep and Sleep Continuity in SSRI-Resistant Depressed Patients
J Clin Psychiatry 2005;66(4):450-454
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The atypical antipsychotic drug olanzapine has been employed as an augmentation treatment in
depressed patients unresponsive to treatment with selective
serotonin reuptake inhibitors (SSRIs). In healthy subjects, acute
olanzapine administration increases sleep continuity and enhances
slow wave sleep (SWS). The aim of the present study was to
determine if the addition of olanzapine to SSRI treatment in
depressed patients produced similar effects on sleep.
Method: We measured the effect of open-label
olanzapine addition (2.5 mg/day initially) on the polysomnograms
of 12 patients referred from primary care sources who met DSM-IV
criteria for major depressive disorder and who had had an
unsatisfactory response to therapeutic doses of an SSRI. Patients
were first enrolled in November 2001; final assessment occurred
in November 2003. Sleep polysomnogram recordings were made on 3
occasions: before olanzapine addition, on the first night of
olanzapine treatment, and after 3 weeks of olanzapine treatment.
Results: After the first night of
olanzapine treatment and during the third week, subjects showed
improvements in sleep efficiency (p < .001), subjective sleep
quality (p < .05), and SWS (p < .01). Scores on the Hamilton
Rating Scale for Depression fell significantly (p = .001), with the
majority of the decrease being apparent after the first week of
Conclusion: Olanzapine improves sleep
continuity and increases SWS in patients receiving SSRI
treatment. These effects are apparent after the first dose of
olanzapine and are maintained for the next 3 weeks. The ability
of olanzapine to increase SWS is probably attributable to 5-HT2A/2C receptor blockade, which has been identified as a relevant
mechanism in the therapeutic effect of olanzapine in
SSRI-resistant depressed patients.