CLOZAPINE IN TARDIVE-DYSKINESIA - OBSERVATIONS FROM HUMAN AND ANIMAL-MODEL STUDIES

Clozapine has long been considered a useful treatment in patients who have schizophrenia with the neuroleptic-induced delayed-onset side eff ect tardive dyskinesia. We present data in support of that clinical im pression using both an animal model of the disorder and dyskinetic pat ients themselves. Clozapine produces a lower rate of oral dyskinesia i n laboratory rats after 6 months of chronic treatment than does halope ridol (8.6 +/- 1.3 vs. 13.6 +/- 1.4 vacuous chewing movements every 5 minutes, respectively), suggesting a lower propensity to cause tardive dyskinesia. In the human, when clozapine was compared with haloperido l in the treatment of patients with tardive dyskinesia, clozapine prod uced significantly greater benefit for motor symptoms after 12 months of treatment than did haloperidol (p < .001). Moreover, the dyskinesia rebound, which occurred equally in both drug groups at the beginning of the study, was sustained in the haloperidol group but lost in the c lozapine-treated patients. These data suggest that dyskinetic patients lose their symptoms of tardive dyskinesia, along with dopaminergic hy persensitivity, with long-term clozapine treatment.