Pharmacotherapy and Pharmaceutical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Clin Psychopharmacol. 2013 Oct;33(5):675-81. doi: 10.1097/JCP.0b013e3182983ffa.
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.
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.
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.
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.
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.
基于多巴胺 D₂ 受体占有率的剂量当量可用于比较抗精神病药的 D₂ 受体介导的（不良）作用，如锥体外系症状和情绪体验改变。以前的基于模型的剂量-占有率关系的荟萃分析几乎没有解决成像数据的潜在异质性。
在解决成像数据潜在异质性的同时，为一系列常用抗精神病药建立剂量与 D₂ 受体占有率的关系模型。
我们对已发表的抗精神病药治疗精神分裂症患者的 D₂ 受体占有率（正电子发射断层扫描和单光子发射计算机断层扫描）数据进行了荟萃分析。通过在模型中纳入研究作为随机效应，以及患者和研究特异性解释变量，非线性混合效应模型估计了特定抗精神病药剂量的中位数 D₂ 受体占有率。通过纳入研究作为随机效应，以及患者和研究特异性解释变量，在模型中对研究间的异质性进行了调查。
共纳入 51 项研究，描述了 606 例患者（平均年龄±标准差，32.2±10.8 岁；25.7%为女性）。模型在治疗剂量范围内用狭窄的置信带描述了剂量-占有率关系。最高占有率（95%置信区间[CI]）估计为氟哌啶醇（91.9%；95%CI，86.1-97.8）、利培酮（92.4%；95%CI，81.8-100）、奥氮平（96.5%；95%CI，85.8-100）、氯氮平（61.7%；95%CI，49.2-74.2）、喹硫平（49.1%；95%CI，18.7-79.6）、阿立哌唑（86.9%；95%CI，78.2-95.7）、齐拉西酮（82.9%；95%CI，44.9-100）和氨磺必利（85.0%；95%CI，68.5-100）。除了研究间存在显著异质性外，个体间差异解释了占有率值的大部分变异性。
所估计的剂量-占有率函数为精神分裂症患者中 8 种常用抗精神病药的多巴胺 D₂ 受体占有率的中位数水平。这些剂量当量可用于在流行病学研究和临床实践中比较抗精神病药的作用。
