Effects of clozapine on sleep measures and sleep-associated changes in growth hormone and cortisol in patients with schizophrenia.

There have been limited reports on the effect of the atypical anti-psychotic agent clozapine on sleep measures and hormone secretion. The goal of this study was to determine the type, rate, and extent of changes in sleep measures and nighttime secretion of growth hormone (GH) and cortisol during clozapine treatment. Five schizophrenic patients (age: 32.4+/-7.4) and five age- and sex-matched normal subjects (age: 33.0+/-5.1) underwent nocturnal polysomnography (NPSG) before clozapine therapy (S1), and during early and late clozapine therapy (S2 and S3). Serum GH and cortisol levels were monitored during each NPSG. NPSG findings showed that the mean total sleep time, sleep efficiency, and duration of awakening were increased at S2, and maintained until S3. The mean amounts of stage 2 sleep at S2 and S3 increased significantly compared with that of S1. In unmedicated schizophrenic patients, the mean plasma GH level in rapid eye movement sleep was lower than during the waking stage, and the mean level of plasma cortisol was higher during the waking stage. Plasma cortisol levels did not differ between control subjects and patients at any time, but clozapine treatment decreased plasma cortisol levels at S2 compared with S1 and S3. Plasma GH levels were unchanged by clozapine treatment. Clozapine improved sleep continuity and increased stage 2 sleep time from the beginning of therapy. These effects were maintained through at least 7 weeks of therapy. However, clozapine did not affect the relationship of plasma GH and cortisol levels with sleep stages in schizophrenic patients.