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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.

Sleep propensity at daytime has not been investigated in untreated patients with schizophrenia. Furthermore, while the antipsychotics clozapine and olanzapine are considered to frequently cause 'sleepiness' or 'sedation', this has not been objectified yet. Therefore, 30 patients with schizophrenia were included in this randomized, double-blind study. Sleep propensity was assessed before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine using a Multiple Sleep Latency Test (MSLT); in the MSLT, sleep latencies of 5 nap opportunities of 20 min during daytime are averaged. In addition, the number of sleep onsets was recorded. Mean sleep latency in untreated schizophrenic patients was 16.2 ± 0.8 min at baseline. Both antipsychotics induced an increase of sleep propensity as indicated by a shortened sleep latency and more sleep onsets during the treatment period as compared to baseline. These effects were strongest in the morning. Four patients receiving clozapine and 3 patients receiving olanzapine reported subjective sleepiness, in all but one commencing in the first treatment week and persisting until study end. While the mean sleep latency during treatment was significantly shorter in these patients (12.3 ± 0.8 min) than in those without subjective sleepiness (14.9 ± 0.7 min), a short sleep latency was not necessarily associated with subjective sleepiness. In conclusion, mean sleep latency was >36% longer (i.e. sleep propensity was lower) in untreated patients with schizophrenia than in healthy subjects previously consistently reported. Furthermore, clozapine and olanzapine increased sleep propensity in schizophrenic patients. A minority of patients reported subjective sleepiness.

Perception of quality of life (QOL) may differ depending on the perspective. This 12-month, prospective, naturalistic study compared QOL ratings in outpatients on antipsychotic treatment for schizophrenia both from a “subjective” patient rated and an “objective” physician rated perspective. Included were 1462 patients. Two scales were used to assess patient and physician perspectives: the Subjective Well-being on Neuroleptics (SWN) scale and the Quality of Life Scale (QLS). Linear correlation was found between both ratings: 10 points on the SWN corresponded to 9.35 points on the QLS. Spearman's correlation coefficients increased over time up to r = 0.71 at Month 12. Patients were grouped into four cohorts depending on the degree of concordance between SWN and QLS ratings. Several factors affecting the concordance of both ratings were identified. Compared to the cohort with QLS = SWN, higher QOL ratings by the physician (QLS ≫ SWN) were more likely in females than in males (OR = 1.36; 95% CI 1.00 – 1.85) and in older than in younger patients (≤ 30 years vs. > 50 years: OR = 0.58, 95% CI 0.34 – 0.998), but less likely in patients with high baseline CGI-severity (CGI > 4; OR = 0.63; 95% CI 0.47 – 0.86) or treatment with oral typicals before baseline (OR = 0.53; 95% CI 0.31 – 0.91). Higher QOL ratings by the patient (SWN ≫ QLS) were less likely in patients with psychotherapy before baseline (OR = 0.54; 95% CI 0.36 – 0.81), medication intolerability before baseline (OR = 0.53; 95% CI 0.36 – 0.78) or patient request of treatment change at baseline (OR = 0.64; 95% CI 0.42 – 0.96). The combination of several factors predicted concordant ratings, including male sex, young age, high CGI at baseline, and psychotherapy prior to the study.