Clozapine and Tardive Dyskinesia

To the Editor: Clozapine is associated with low rates of extrapyramidal side effects and is thought to have a minimal risk of tardive dyskinesia. Furthermore, clozapine has been shown to significantly diminish dyskinetic movements in patients with tardive dyskinesia and is considered an effective treatment for it (1). Despite these observations suggesting clozapine’s benefits, there have been several case reports of tardive dyskinesia associated with clozapine. Several reports (2–4) have involved patients who received previous treatment with typical antipsychotics. The following report describes clozapine-related tardive dyskinesia appearing after 10 years of treatment with clozapine in a woman who had had minimal exposure to typical antipsychotics.

This case suggests that long-term treatment with clozapine may be associated with tardive dyskinesia in an individual with minimal exposure to conventional antipsychotics. Since the patient had approximately 2 years of exposure to typical antipsychotics before starting to take clozapine, their contribution cannot be discounted. Given that the patient had no evidence of involuntary movements before clozapine treatment and that she received clozapine for approximately 10½ years before the onset of tardive dyskinesia, the impact of typical antipsychotics is likely to be minimal at most. It is possible that the patient’s dyskinesia would have occurred spontaneously in the absence of antipsychotic exposure, but this is unlikely. In conclusion, clozapine and the other atypical antipsychotic drugs appear to have greatly reduced the liability for tardive dyskinesia, but it appears that they have not totally eliminated the risk.