alexa Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Nyberg S, Eriksson B, Oxenstierna G, Halldin C, Farde L

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Abstract OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82\% (range = 79\%-85\%), 5-HT2A receptor occupancy was 95\% (range = 86\%-109\%), and six patients had developed extrapyramidal side effects. After dose reduction to 3 mg/day, D2 receptor occupancy was 72\% (range = 53\%-78\%), and 5-HT2A receptor occupancy was 83\% (range = 65\%-112\%). Three patients had extrapyramidal side effects at this time. CONCLUSIONS: Treatment with risperidone, 6 mg/day, is likely to induce unnecessarily high D2 receptor occupancy, with a consequent risk of extrapyramidal side effects. High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely. The authors previously suggested an optimal interval for D2 receptor occupancy of 70\%-80\%. To achieve this, resperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients. This article was published in Am J Psychiatry and referenced in Journal of Clinical & Experimental Pharmacology

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