Positron emission tomography studies on D2 and 5-HT2 receptor binding in risperidone-treated schizophrenic patients.

By the use of positron emission tomography (PET), high central dopamine D 2 receptor occupancy (70 to 90%) has been demonstrated in patients treated with conventional neuroleptics. In patients treated with the atypical antipsychotic clozapine, the D 2 occupancy was low (20 to 67%). The effects of clozapine may thus be mediated by a mechanism distinct from D 2 occupancy. The observation that low doses of clozapine (125 to 175 mg daily) induced more than 80% (5-hydroxytryptamine) 5-HT 2 occupancy supports the view that 5-HT 2 antagonism may be related to the atypical effects of clozapine. Risperidone is a new antipsychotic drug with high affinity in vitro for both central 5-HT 2 and D 2 receptors. In this study, we determined the D 2 and 5-HT 2 occupancy induced by clinical treatment with risperidone. Four patients with acute exacerbation of schizophrenia were examined by PET after 4 weeks of treatment with risperidone, 6 mg daily. The D 2 occupancy in the striatum was 75 to 80%. The 5-HT 2 occupancy in the neocortex was 78 to 88%. This study confirms that, in patients with schizophrenia, treatment with risperidone induces a high D 2 and 5-HT 2 occupancy. Risperidone is, accordingly, a suitable drug for the examination of the clincial benefit of combined serotonin and dopamine antagonism