期刊
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
卷 33, 期 5, 页码 675-681出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/JCP.0b013e3182983ffa
关键词
dopamine D-2 receptor occupancy; antipsychotic dose; schizophrenia; positron emission tomography (PET) imaging study
资金
- Christian Fellowship of Care for Mental and Neurological Disorders (VCVGZ)
- Dutch Foundation for Mental Health
- Mental Health Care Centre (GGZ) Drenthe
Rationale: Dose equivalents based on dopamine D-2 receptor occupancy can be used to compare antipsychotics on D-2 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 D-2 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 D-2 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 D-2 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 D-2 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.
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