TREATMENT OF SEVERE AXIAL TARDIVE DYSTONIA WITH CLOZAPINE - CASE-REPORT AND HYPOTHESIS

We report a patient with severe axial tardive dystonia who has had dra matic improvement for 4 years after treatment with the atypical antips ychotic drug clozapine (625 mg/day). Clozapine differs from convention al neuroleptics in that it has higher affinity for D1 and lower affini ty for D2 dopamine receptors than do conventional antipsychotics, whic h are relatively selective D2 antagonists. We propose that repetitive stimulation of the D1 receptor by endogenous dopamine, resulting in se nsitization of the D1-mediated striatal output in the presence of D2 r eceptor blockade, is a fundamental mechanism mediating tardive dyskine sia, including the dystonic type. According to this hypothesis, it is primarily the D1 antagonist action of clozapine that accounts for its inability to cause tardive dyskinesia as well as its therapeutic effec t in tardive dystonia. Regardless of its mechanism of action, the sust ained improvement observed in this case suggests that clozapine should be tried in cases of severe refractory tardive dystonia.