Estimating dopamine D2 receptor occupancy for doses of 8 antipsychotics : a meta-analysis

Rationale. Dose equivalents based on dopamine D2 receptor occupancy can be used to compare antipsychotics on D2 receptor-mediated (adverse) effects such as extrapyramidal symptoms and altered emotionalexperiences. Previous meta-analyses modeling the dose-occupancy relationship hardly addressed potential heterogeneity of the imaging data. Objectives. To model the relationship between dose and D2 receptor occupancy for a series of frequently prescribed antipsychotics while addressing the potential heterogeneity of the imaging data. Methods. We conducted a meta-analysis on published D2 receptor occupancy data (positron emission tomography and single-photon emission computed tomography) in patients with schizophrenia treated with antipsychotics. A nonlinear mixed effects model estimated the median D2 receptor occupancy for a given antipsychotic dose. Heterogeneity between studies was investigated by incorporating study as a random effect in the model, in addition to patient- and study-specific explanatory variables. Results. Included were 51 studies, describing 606 patients (mean ± SD age, 32.2 ±10.8 years; 25.7% female). The models described the dose-occupancy relationship with narrow confidence bands around the therapeuticdose range. Maximum occupancy (95% confidence interval[CI]) was estimated for haloperidol (91.9%; 95% CI, 86.1–97.8), risperidone(92.4%; 95% CI, 81.8–100), olanzapine (96.5%; 95% CI,85.8–100), clozapine (61.7%; 95% CI, 49.2–74.2), quetiapine (49.1%; 95% CI, 18.7–79.6), aripiprazole (86.9%; 95% CI, 78.2–95.7), ziprasidone (82.9%; 95% CI, 44.9–100), and amisulpride (85.0%; 95% CI, 68.5–100). Interindividual differences explained most of the variability in occupancy values, besides significant heterogeneity between studies. Conclusions. Dose-occupancy functions estimated the median level of dopamine D2 receptor occupancy for 8 frequently prescribed antipsychotics in patients with schizophrenia. These dose equivalents can be used to compare antipsychotic effects in epidemiological studies and clinical practice.