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.
From the *Pharmacotherapy and Pharmaceutical Care, †Rob Giel Onderzoekscentrum, University Medical Center Groningen, ‡Department of Epidemiology, University Medical Center Groningen, §Lentis Center for Mental Health Care and Neuroimaging Center, and ∥Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Received April 20, 2012; accepted after revision December 31, 2012.
Reprints: Katja Taxis, PhD, Division Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen, Groningen, A. Deusinglaan 1, Groningen, 9713AV, The Netherlands (e-mail: email@example.com).
This study was funded by the Christian Fellowship of Care for Mental and Neurological Disorders (VCVGZ), the Dutch Foundation for Mental Health, and the Mental Health Care Centre (GGZ) Drenthe for their unconditional grants.
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