Olanzapine increases slow wave sleep and sleep continuity in SSRI-resistant depressed patients

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.

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.

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 treatment.

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-HT(2A/2C) receptor blockade, which has been identified as a relevant mechanism in the therapeutic effect of olanzapine in SSRI-resistant depressed patients.