Autonomic effects of clozapine in schizophrenia: comparison with placebo and fluphenazine

Peripheral indicators of autonomic nervous system activity, including electrodermal activity and heart rate, were studied in 25 chronic schizophrenic patients given clinical trials of clozapine, a standard neuroleptic (fluphenazine), and placebo. The protocol included a rest period, presentation of nonsignal tones, and a reaction time task. Clozapine markedly attenuated electrodermal base levels and both phasic and tonic electrodermal responsivity compared to placebo, and somewhat less consistently compared to fluphenazine. Both electrodermal and vasoconstrictive orienting responses to tones were reduced. Elevated heart rate and reduced heart rate variability were also observed in patients taking clozapine. Many of these effects can be accounted for by clozapine's anticholinergic and antihistaminic properties. There was evidence that a smaller autonomic response to the mild stress of task performance and larger heart rate responses to nonsignal tones on the alternate treatments were predictive of a good clinical response to clozapine. These results suggest that when on alternate treatments good clozapine responders show more psychophysiological signs of pathology than clinical nonresponders.