An Investigation of the Sleep Architecture in Ziprasidone-Treated Bipolar Depression
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Objective: To primarily determine the effect of ziprasidone augmentation therapy on sleep architecture, specifically slow wave sleep (SWS) and rapid eye movement sleep (REM), in the treatment of bipolar depression. Secondarily, to determine the effect of ziprasidone augmentation treatment on clinical measures of subjective sleep quality and illness severity. Finally, to examine the correlation between change in sleep architecture and change in clinical measures. Methods: This was a prospective, double-blind, randomized, placebo-controlled study. 14 patients with bipolar disorder currently experiencing a major depressive episode were included. Patients were on a stable medication regime for 4 weeks prior to study enrollment and throughout the study. Sleep architecture was measured by overnight, ambulatory polysomnography. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and a visual analogue scale. Illness severity was determined using the 17 item Hamilton Depression Rating Scale (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAMA) and the Clinical Global Impression-Severity scale (CGI-S). Polysomnographs and clinical measures were administered at baseline, after 2-5 days and after 28-31 days of treatment. Results: There was no significant difference between ziprasidone and placebo treated groups on age, gender, diagnosis, education level, employment or marital status and number of children. Duration of SWS, latency to REM, duration of stage 2 sleep, total sleep time, onset to sleep latency, sleep efficiency and number of awakenings significantly improved in ziprasidone treated participants over placebo, whereas duration of REM sleep did not. CGI-S and HAMA scores were significantly improved with ziprasidone treatment. No significant difference between treatment groups was seen on the HAMD-17 and MADRS or in self-reported sleep quality. Change in REM sleep significantly correlated to change in subjective sleep quality in the ziprasidone group. Conclusion: Ziprasidone augmentation treatment in bipolar depression improves SWS duration, REM latency, and sleep continuity while also having a beneficial effect on overall illness severity and anxiety symptoms.