Olanzapine and clozapine differently affect sleep in patients with schizophrenia: Results from a double-blind, polysomnographic study and review of the literature

Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.