Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy.
Clinical Pharmacology Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences L, Sacco University Hospital, Università degli Studi di Milano, Milan, Italy.
World J Biol Psychiatry. 2021 Jan;22(1):34-45. doi: 10.1080/15622975.2020.1747112. Epub 2020 May 6.
Exposure and clinical response to CNS drugs are largely variable. AGNP guidelines suggest therapy individualisation with therapeutic drug monitoring of plasma concentrations and pharmacogenetic testing. We present the retrospective analysis of the last 5 years' data collected in real life settings as indirect evidence of the applications of the AGNP guidelines in the routine clinical management of psychiatric patients requiring pharmacologic treatments.
Plasma concentrations were quantified using a liquid chromatography/tandem mass spectrometry method. Genomic DNA was isolated using an automatic DNA extraction system. All genotypes were determined by Real-Time PCR.
We collected a total of 4582 requests for TDM and 212 requests for pharmacogenetic analysis. A wide distribution in the trough concentrations was observed for most drugs indicating a high interpatient variability. Nearly 45% of the samples had trough levels below the minimum effective drug concentrations set by the AGNP guidelines; only 8% of the samples had high concentrations. For pharmacogenetics analysis, among antipsychotics, clozapine, haloperidol and aripiprazole were the most requested (78%); while for antidepressants SSRIs were the most frequently prescribed.
These data suggest that physicians are becoming more confident with the laboratory pharmacologic tools to optimise treatments and/or that the pharmacological treatment of patients with psychiatric disorders is becoming more challenging. TDM and PGx might significantly contribute to the rational selection of the best drug and best dose in individual cases.
中枢神经系统（CNS）药物的暴露和临床反应在很大程度上是可变的。AGNP 指南建议通过监测血浆浓度和药物遗传学检测进行个体化治疗。我们呈现了过去 5 年在真实环境中收集的数据的回顾性分析，作为 AGNP 指南在需要药物治疗的精神科患者常规临床管理中应用的间接证据。
使用液相色谱/串联质谱法定量血浆浓度。使用自动 DNA 提取系统分离基因组 DNA。通过实时 PCR 确定所有基因型。
我们共收集了 4582 份 TDM 请求和 212 份药物遗传学分析请求。大多数药物的谷浓度分布广泛，表明患者间的变异性很高。近 45%的样本的谷浓度低于 AGNP 指南设定的最低有效药物浓度；只有 8%的样本浓度较高。对于药物遗传学分析，在抗精神病药物中，氯氮平、氟哌啶醇和阿立哌唑的需求量最大（78%）；而在抗抑郁药中，SSRIs 是最常开的处方。
这些数据表明，医生对实验室药理学工具越来越有信心，以优化治疗，或者精神障碍患者的药物治疗变得更加具有挑战性。TDM 和 PGx 可能会显著有助于在个体病例中选择最佳药物和最佳剂量。
