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 language | English |
|---|---|
| Pages (from-to) | 1281-1286 |
| Number of pages | 6 |
| Journal | Journal of Clinical Psychiatry |
| Volume | 69 |
| Issue number | 8 |
| Publication status | Published - 2008 Aug |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia
AU - Uchida, Hiroyuki
AU - Mamo, David C.
AU - Kapur, Shitij
AU - Labelle, Alain
AU - Shammi, Chekkera
AU - Mannaert, Erik J L
AU - Mann, Steve W.
AU - Remington, Gary
PY - 2008/8
Y1 - 2008/8
N2 - 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
AB - 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
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M3 - Article
VL - 69
SP - 1281
EP - 1286
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
SN - 0160-6689
IS - 8
ER -