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

J Clin Psychiatry. 2008 Aug;69(8):1281-6. doi: 10.4088/jcp.v69n0811.


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: Identifier: NCT00236353.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Delayed-Action Preparations
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / metabolism
  • Receptors, Dopamine D2 / metabolism*
  • Risperidone / administration & dosage
  • Risperidone / blood
  • Risperidone / therapeutic use*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism*


  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Receptors, Dopamine D2
  • Risperidone

Associated data