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 journalArticle

40 Citations (Scopus)

Abstract

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: clinicaltrials.gov Identifier: NCT00236353

Original languageEnglish
Pages (from-to)1281-1286
Number of pages6
JournalJournal of Clinical Psychiatry
Volume69
Issue number8
Publication statusPublished - 2008 Aug
Externally publishedYes

Fingerprint

Corpus Striatum
Risperidone
Dopamine D2 Receptors
Schizophrenia
Injections
Positron-Emission Tomography
Antipsychotic Agents
Raclopride
Diagnostic and Statistical Manual of Mental Disorders
Psychotic Disorders
Dopamine
Maintenance
Clinical Trials

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia. / Uchida, Hiroyuki; Mamo, David C.; Kapur, Shitij; Labelle, Alain; Shammi, Chekkera; Mannaert, Erik J L; Mann, Steve W.; Remington, Gary.

In: Journal of Clinical Psychiatry, Vol. 69, No. 8, 08.2008, p. 1281-1286.

Research output: Contribution to journalArticle

Uchida, H, Mamo, DC, Kapur, S, Labelle, A, Shammi, C, Mannaert, EJL, Mann, SW & Remington, G 2008, 'Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia', Journal of Clinical Psychiatry, vol. 69, no. 8, pp. 1281-1286.
Uchida, Hiroyuki ; Mamo, David C. ; Kapur, Shitij ; Labelle, Alain ; Shammi, Chekkera ; Mannaert, Erik J L ; Mann, Steve W. ; Remington, Gary. / Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia. In: Journal of Clinical Psychiatry. 2008 ; Vol. 69, No. 8. pp. 1281-1286.
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