Clozapine and tardive dyskinesia: analysis of clinical trials

Abstract

Tardive dyskinesia (TD) is a disabling disorder associated with neuroleptic-treatment. Despite the existence of many different therapeutic strategies, TD is often refractory to any treatment. The atypical neuroleptic Clozapine, associated with a relatively low rate of parkinsonism and TD, may have a particular role in the management of neuroleptic-induced TD. The present study will critically analyze the results of the different studies relating to Clozapine's efficacy in TD and its mechanisms. Focus will be on trials wherein the main indication for clozapine's use was the management of TD. Ten of the fourteen relevant studies evaluated, primarily of open design, demonstrated considerable reduction with Clozapine in TD symptomatology in significant proportion of the patients. The dosage required was high, the treatment period long, and cessation of medication was associated with a significant rebound-effect. Clozapine may be efficient in the management of TD. Placebo-controlled designs, employing different dose regiments are required to further establish the role of Clozapine in this disabling disorder.