Efficacy of clozapine on dopamine supersensitivity psychosis in schizophrenia

Although the effectiveness of clozapine (CLZ) for patients with treatment-resistant schizophrenia (TRS) has been well established, its active mechanism has not been completely clarified. Several clinical studies showed that neuroleptic-induced dopamine supersensitivity psychosis (DSP) could be involved in the etiology of TRS. We preliminarily explored the possible beneficial effect of CLZ for dopamine supersensitivity schizophrenia. The present study is a case series. We followed 15 patients with DSP for about 2.5 years from the introduction of CLZ and compared the prevalence of episodes (particularly, rebound psychosis, tolerance to antipsychotic effects, or tardive dyskinesia) between the period before and during CLZ treatment. Our observation over 2.5 years following the introduction of CLZ showed that 13 of the 15 DSP patients presented no further DSP episodes. One patient showed continued tardive dyskinesia, which had already existed in the preperiod, and the other patient presented with rebound psychosis that appeared immediately after discontinuation of CLZ. The results of the present study indicated that DSP in schizophrenic patients treated with general antipsychotics disappeared over the subsequent 2.5 years under CLZ treatment, suggesting that the agent ameliorates the dopamine supersensitivity state induced by previous antipsychotic treatment.