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

Hiroyuki Uchida, David C. Mamo, Shitij Kapur, Alain Labelle, Chekkera Shammi, Erik J.L. Mannaert, Steve W. Mann, Gary Remington

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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 D2 binding of long-acting risperidone administered intramuscularly once a month. Method: Following at least 3 maintenance monthly injections of 50 mg long-acting risperidone, 7 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder underwent PET using [11C]raclopride to measure D2 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 D2 receptor occupancy was 56% ± 24% (range, 29%-82%). Of note, there were 4 subjects with less than 60% D2 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 D2 occupancy levels for individuals receiving long-acting risperidone. This work suggests a possibility that sustained D2 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: Identifier: NCT00236353

Original languageEnglish
Pages (from-to)1281-1286
Number of pages6
JournalJournal of Clinical Psychiatry
Issue number8
Publication statusPublished - 2008 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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