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 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 ± SD age, 32.2 ±10.8 years; 25.7% female). The models described the dose-occupancy relationship with narrow confidence bands around the therapeutic dose range. Maximum occupancy (95% confidence interval[CI]) was estimated for haloperidol (91.9%; 95% CI, 86.1-97.8), 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.