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


METHODS
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).


CONCLUSIONS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00236353.
Uchida
Hiroyuki
H
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Mamo
David C
DC
Kapur
Shitij
S
Labelle
Alain
A
Shammi
Chekkera
C
Mannaert
Erik J L
EJ
Mann
Steve W
SW
Remington
Gary
G
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003692:Delayed-Action Preparations; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D017448:Receptors, Dopamine D2; D018967:Risperidone