Yale Child Study Center, New Haven, CT, United States.
Yale Child Study Center, Department of Psychiatry, Yale University, New Haven, CT, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):272-281. doi: 10.1016/j.pnpbp.2018.01.023. Epub 2018 Feb 2.
Our objective was to examine the association between antipsychotic receptor binding profiles and the magnitude of common side-effects. We used regression analysis to examine the association between the receptor binding affinities of antipsychotic agents (log Ki) and degree of specific antipsychotic side-effects. Data on magnitude of weight gain, prolactin increase and QTc prolongation (in Standardized Mean Difference) and risk of sedation and extrapyramidal symptoms (in Odds Ratio) between individual antipsychotic medications as compared to placebo was based on a recent network meta-analysis examining the treatment of schizophrenia. Receptor affinities (in log Ki) were examined for the D2, 5-HT1A, 5-HT2A, 5-HT2C, H1, alpha1, alpha2, M1, M3 and M4 receptors. Medications were weighted in the analysis using the generic inverse variance method utilizing variance estimates from the previous meta-analysis. Magnitude of weight gain was significantly associated with the affinity of antipsychotic medications to M1, M3, 5-HT2C and H1 receptors. Risk of sedation was significantly associated with the affinity to the M1 and M4 receptors. Magnitude of hyperprolactinemia was significantly associated with the affinity to M1 and M4 receptors. Risk of extrapyramidal side effects was associated with the affinity to 5-HT2C and M1 receptors. QT prolongation was not significantly associated with antipsychotic receptor affinities. Our meta-analysis demonstrated that increased affinity of antipsychotics for certain receptors are significantly associated with higher risk of sedation, hyperprolactinemia, extrapyramidal side effects and weight gain.
我们的目的是检验抗精神病药受体结合谱与常见副作用严重程度之间的关联。我们使用回归分析来检验抗精神病药物（Ki 对数）的受体结合亲和力与特定抗精神病副作用严重程度之间的关联。体重增加、催乳素升高和 QTc 延长的幅度（以标准化均数差表示）以及镇静和锥体外系症状风险（以比值比表示）的数据，是基于最近一项针对精神分裂症治疗的网络荟萃分析。受体亲和力（Ki 对数）针对 D2、5-HT1A、5-HT2A、5-HT2C、H1、alpha1、alpha2、M1、M3 和 M4 受体进行了检查。在分析中，使用来自先前荟萃分析的方差估计，使用通用倒数方差法对药物进行加权。体重增加幅度与抗精神病药物对 M1、M3、5-HT2C 和 H1 受体的亲和力显著相关。镇静风险与 M1 和 M4 受体的亲和力显著相关。高催乳素血症的幅度与 M1 和 M4 受体的亲和力显著相关。锥体外系副作用的风险与 5-HT2C 和 M1 受体的亲和力相关。QT 延长与抗精神病药受体亲和力无显著相关性。我们的荟萃分析表明，抗精神病药对某些受体的亲和力增加与镇静、高催乳素血症、锥体外系副作用和体重增加的风险增加显著相关。
