A psychophysiological investigation of the long-term effects of clozapine upon sleep patterns of normal young adults.

A 25-night single-blind cross over design was employed to determine the long-term effects of clozapine on the sleep patterns of six normal young adults. Subjects received 12.50 mg placebo on the first and last five nights, whereas on the intermediate 15 nights 12.5 mg clozapine was administered. The subjects slept in the laboratory on the third and fourth nights to obtain baseline recordings, and on the eight, twelfth, sixteenth, and twentieth nights to determine the effects of clozapine on sleep variables. Recordings on nights 21 and 25 were used to assess withdrawal effects. Percentage stage 1 sleep and indices of body movements during sleep were significantly reduced, suggesting that clozapine may have sleep-inducing properties. There were no significant rebound of stage REM sleep during drug withdrawal despite a small but significant reduction in stage REM during drug administration. Numerous side effects, indicative of sleepiness, were reported on the mornings following drug administration, and there was evidence of a rapid tolerance to clozapine. These findings may limit the efficacy of clozapine as an hypnotic agent over an extended period of time. Further research on insomniac subjects is therefore indicated.