den Uil Manon G, Hut Hannelotte W, Wagelaar Kay R, Abdullah-Koolmees Heshu, Cahn Wiepke, Wilting Ingeborg, Deneer Vera H M
Division Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, Netherlands.
Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, Netherlands.
Front Genet. 2023 Aug 25;14:1249164. doi: 10.3389/fgene.2023.1249164. eCollection 2023.
Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of and can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the side effects rating scale (UKU). Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for and respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients ( = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of experienced the side effect depression compared to 30.4% NMs and UMs ( = 0.020). IM and PM patients had a higher concentration-dose ratio than NM patients ( < 0.05). This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.
预防副作用对于确保精神科患者获得最佳的精神药物治疗及治疗依从性至关重要。获取[药物名称1]和[药物名称2]的药物遗传学特征在这方面可发挥重要作用。当由于联合用药导致基因型预测的表型发生改变时，这被称为表型转换。本研究旨在探讨药物遗传学（PGx）特征和表型转换对精神科患者所经历副作用的影响。使用一家精神科门诊117例患者的数据进行了一项回顾性队列研究。患者通过精神科PGx检测板进行基因分型，并使用[副作用评定量表名称]副作用评定量表评估副作用。在所有患者中，分别有10.3%和9.4%的[药物名称1]和[药物名称2]发生了表型转换（预测表型的任何改变）。未发现表型与UKU评分之间存在显著关联。[药物名称1]代谢中间型（IM）或代谢不良型（PM）表型的患者中有75%经历了恶心和呕吐，而正常代谢型（NM）和超快代谢型（UM）患者的这一比例为9.1%（P = 0.033）。[药物名称2]代谢中间型（IM）或代谢不良型（PM）表型的患者中有64%经历了抑郁副作用，而正常代谢型（NM）和超快代谢型（UM）患者的这一比例为30.4%（P = 0.020）。IM和PM患者的浓度-剂量比高于NM患者（P < 0.05）。本研究强调了在查看患者基因型时考虑表型转换的重要性。这对于更好地预测表型以及预防特定精神药物治疗下可能出现的副作用非常重要。
