Estimating Dopamine D2 Receptor Occupancy for Doses of 8 Antipsychotics

作者：Irene M. Lako, Edwin R. van den Heuvel, Henrikus Knegtering, Richard Bruggeman, Katja Taxis · 发表于：Journal of Clinical Psychopharmacology · 年份：2013 · DOI：10.1097/jcp.0b013e3182983ffa · 被引用次数：126 · 研究领域：Schizophrenia research and treatment、Medical Imaging Techniques and Applications、Treatment of Major Depression

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, ...