Gating of auditory P50 in schizophrenics: unique effects of clozapine

Schizophrenic patients have a deficit in the ability to filter sensory stimuli, which can be demonstrated in several psychophysiological paradigms. For example, most unmedicated schizophrenic subjects fail to decrement the P50 auditory evoked response to the second of paired stimuli, when the interstimulus interval is 500 msec. This sensory gating deficit persists in schizophrenics treated with typical antipsychotics, even if they show significant clinical improvement. When the interstimulus interval is 100 msec, most schizophrenics exhibit impaired gating while acutely ill, but normalize with treatment. Clozapine, the prototypic atypical antipsychotic medication, is clinically more effective than conventional neuroleptics in a significant proportion of schizophrenics refractory to other drug treatment. Nine schizophrenic subjects who were refractory to conventional neuroleptic treatment were studied while being treated with typical neuroleptics and then restudied after 1 month's treatment with clozapine. In the six clozapine responders, there was significant improvement of P50 gating at the 500 msec interval. At the 100 msec interval there was an inverse relationship between sensory gating of P50 and clozapine dose, independent of clinical response. Thus, although this can only be considered preliminary data because of the small number of subjects, it appears that clozapine, compared to typical neuroleptics, has distinct effects on P50 gating.