A long-acting depot formulation of
olanzapine that sustains plasma
olanzapine concentrations for over a month after a single injection is currently under development. This multicenter, open-label study explored D(2) receptor occupancy of a fixed dose of
olanzapine pamoate (OP) depot given every 4 weeks. Patients (nine male, five female) with
schizophrenia or
schizoaffective disorder previously stabilized on oral
olanzapine were switched to OP depot 300 mg by
intramuscular injection every 4 weeks for 6 months. No visitwise within-group significant changes were found in Brief Psychiatric Rating Scale Total or Clinical Global Impressions-Severity of Illness scores, although seven patients received oral
olanzapine supplementation during the first four injection cycles. To minimize impact on D(2) occupancy, positron emission tomography (PET) scans were not completed during injection cycles that required supplemental oral
olanzapine. Two patients reported transient injection site adverse events, which did not result in discontinuation. The most frequently reported treatment-emergent adverse events were
insomnia, aggravated
psychosis, and anxiety. Mean striatal D(2) receptor occupancy, as measured by [(11)C]-
raclopride PET, was 69% on oral
olanzapine (5-20 mg/day) and 50% (trough) on OP depot at steady state. Following an initial decline, occupancy returned to 84% of baseline oral
olanzapine occupancy after six
injections. Over the study period, D(2) receptor occupancy and plasma
olanzapine concentrations were significantly correlated (r=0.76, P</=0.001). OP depot resulted in mean D(2) receptor occupancy of approximately 60% or higher at the end of the 6-month study period, a level consistent with
antipsychotic efficacy and found during treatment with oral
olanzapine. However, supplemental oral
olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles.