Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia: A cross-sectional study

In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia.