Tardive dyskinesia, clozapine and treatment response

Tardive dyskinesia (TD) remains a serious limitation in the use of antipsychotic medications to treat psychotic illnesses. While all typical antipsychotic medications have been associated with the development of TD, the atypical antipsychotic, clozapine, appears less likely to cause TD and may even ameliorate existing TD (Lieberman et al 1991). In a retrospective chart review, we examined the relationship among TD, clozapine treatment and treatment response among patients receiving clozapine at the Ann Arbor VAMC. The thirteen subjects were all male, mean age 43.9 ± 6.0 years. Prior to starting clozapine, 12 of the 13 met criteria for refractory illness; one subject had severe and disabling tardive dystonia. Six subjects had a diagnosis of TD at the beginning of clozapine treatment. There was also a trend for subjects with TD to have more symptoms on BPRS rating at baseline. BPRS and AIMS results were analyzed for subjects grouped by diagnosis of TD (present or absent) at baseline using 2-tailed paired t-tests (self as own control). At baseline, subjects with TD had a BPRS total score of 60.7 ± 3.9 and AIMS score (sum items 1-7) of 12.2 ± 4.1. They received an average clozapine dose of 358 ± 196 mg for 10.2 ± 5.6 months. At follow-up, their average BPRS score was 32.8 ± 10.4 (t=5.7; p<0.01), and AIMS score was 1.8 ± 1.9 (t=6.1; p<0.01). Subjects without TD at baseline also showed a decrease in BPRS scores (baseline 52.0 ± 9.0; follow-up 30.3 ± 8.0; t=4.8; p<0.01) after receiving a mean clozapine dose of 489 ± 258 mg for 17.1 ± 9.8 months. AIMS scores in this group showed no significant change (baseline 1.7 ± 1.3; follow-up 0.71 ± 0.95; t=1.62; p=NS). The lack of a randomized, double-blind design limits our conclusions. However, our results suggest a clinically and statiscally significant effect of clozapine on TD in a group of chronically psychotic patients, and underscore the striking utility of clozapine in those with significant TD.