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Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia.

Author(s): Uchida H, Mamo DC, Kapur S, Labelle A, Shammi C, Mannaert EJ, Mann SW, Remington G

Affiliation(s): Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Publication date & source: 2008-08, J Clin Psychiatry., 69(8):1281-6.

Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVE: Long-acting risperidone administered intramuscularly biweekly is approved for the management of schizophrenia. However, dosing of long-acting antipsychotics is frequently extended in clinical practice, and a recent clinical trial has lent support to monthly dosing of long-acting risperidone. The objective of this positron emission tomography (PET) study was to examine the striatal dopamine D(2) binding of long-acting risperidone administered intramuscularly once a month. METHOD: Following at least 3 maintenance monthly injections of 50 mg long-acting risper-idone, 7 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder under-went PET using [(11)C]raclopride to measure D(2) binding potential within 4 days of the next scheduled injection. Data were collected from May to October 2003. This PET study was part of a larger 52-week clinical study wherein individuals received long-acting risperidone once monthly over a 1-year interval. One-year follow-up data were obtained from the 52-week parent investigation. RESULTS: The mean +/- SD D(2) receptor occupancy was 56% +/- 24% (range, 29%-82%). Of note, there were 4 subjects with less than 60% D(2) occupancy, none of whom relapsed over the course of the 1-year follow-up. The mean +/- SD total plasma level of risperidone plus 9-hydroxyrisperidone was 16.6 +/- 12.3 ng/mL (range, 5.7-40.8). CONCLUSION: As with plasma levels, there was considerable variability in D(2) occupancy levels for individuals receiving long-acting risperidone. This work suggests a possibility that sustained D(2) occupancy at or above the accepted threshold with acute clinical response may not be necessary to maintain response, a hypothesis with important clinical implications as we consider antipsychotic dosing and future antipsychotic development. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00236353.

Page last updated: 2008-11-03

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