Estimating Dopamine D 2 Receptor Occupancy for Doses of 8 Antipsychotics
2014
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 emotional experiences. 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 T SD age, 32.2 T10.8 years; 25.7% female). The models described the doseoccupancy relationship with narrow confidence bands around the therapeutic dose range. Maximum occupancy (95% confidence interval [CI]) was estimated for haloperidol (91.9%; 95% CI, 86.1Y97.8), risperidone (92.4%; 95% CI, 81.8Y100), olanzapine (96.5%; 95% CI, 85.8Y100), clozapine (61.7%; 95% CI, 49.2Y74.2), quetiapine (49.1%; 95% CI, 18.7Y79.6), aripiprazole (86.9%; 95% CI, 78.2Y95.7), ziprasidone (82.9%; 95% CI, 44.9Y100), and amisulpride (85.0%; 95% CI, 68.5Y100). 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
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