Abstract
The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean +/- SD final dosage: 5.8 +/- 3.8 mg) or olanzapine (mean +/- SD final dosage: 13.6 +/- 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean +/- SEM pre-treatment value: 6.7 +/- 20.3%; after-treatment: 85.7 +/- 10.9%), total wake time (pre-treatment: 140.0 +/- 92.5 min; after-treatment: 55.2 +/- 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 +/- 70.8 min; after-treatment: 32.2 +/- 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.
Highlights
Sleep disturbances are prominent clinical features of manic states
Some discrepant findings have been reported [1,2,3], polysomnographic (PSG) studies of manic patients have consistently revealed a number of abnormalities, including significantly decreased total-recording period, decreased time spent asleep, decreased sleep efficiency, shortened rapid eye movement (REM) latency, and increased REM density compared to their pre-morbid state [4,5,6,7,8] and compared to controls [9,10]
The group treated with olanzapine showed a significant (P < 0.05) decrease from the beginning to the end of the experiment in both Young Mania Rating Scale (YMRS) total scores and Clinical Global Impressions - Bipolar version (CGI-BP) scores
Summary
Sleep disturbances are prominent clinical features of manic states. Antipsychotic drugs have been prescribed for bipolar disorder patients for several decades as the treatment for psychotic symptoms or as an adjunctive therapy when other alternatives have failed, such as lithium and other mood-stabilizing drugs. The search for new drugs for the treatment of bipolar disorder has identified the novel atypical antipsychotic agent olanzapine, which has shown superior efficacy when compared with placebo in clinical trials [13] and seems to be as effective as lithium in treating acute mania [14]. The main PSG finding for olanzapine tested on healthy subjects is an increase of slow-wave sleep [16,17,18]
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