Effects of typical and atypical antipsychotics on the prepulse inhibition of the startle reflex in patients with schizophrenia

Abstract

Patients with schizophrenia show a loss of sensory (motor) gating, which is reflected in a reduced prepulse inhibition (PPI) of the startle reflex. Furthermore, patients with schizophrenia habituate less than healthy subjects. From previous studies, it is clear that typical antipsychotics have little or no effect on either sensorimotor gating or habituation, while only limited data is available on the effects of atypical antipsychotics on these processes. Forty-four schizophrenic patients (27 stable on typical and 17 stable on atypical antipsychotics) and 35 healthy control subjects were tested in a PPI paradigm. The prepulse and startle stimuli were pure tones of 1500 Hz (duration 40ms, intensity 80 dB and 110 dB respectively), with a fixed interstimulus interval of 120 milliseconds. Block effects in PPI and startle amplitude to the pulse alone trials (habituation) were analyzed over the three groups, using comedication (i.e., benzodiazepines) as a covariate. Main effect for block was found for startle amplitude (habituation), while main effects for group and block were found for percentage PPI. Further analysis displayed significant differences in PPI between the patients treated with typical antipsychotics and the healthy control group, while patients treated with atypical antipsychotics did not differ from either the healthy control group, or the patients treated with typical antipsychotics. Furthermore, post-hoc division of the patients treated with atypical antipsychotics in patients treated with clozapine and risperidone revealed that this superiority from atypical antipsychotics over typical antipsychotics appeared to be mainly based on the effects of clozapine. Patients with schizophrenia who are treated with atypical antipsychotics appear to have levels of sensorimotor gating that are more consistent with healthy controls than patients who are treated with typical antipsychotics. Furthermore, within the class of atypical antipsychotics, clozapine appears most potent in restoring this process.