Bousman Chad A, Dunlop Boadie W
Department of Psychiatry, The University of Melbourne, Carlton South, VIC, Australia.
Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada.
Pharmacogenomics J. 2018 Sep;18(5):613-622. doi: 10.1038/s41397-018-0027-3. Epub 2018 May 25.
The degree of agreement between four commercial pharmacogenetic-based decision support tools (DSTs) was examined in five outpatients with major depressive disorder and at least two previous antidepressant failures. Comparisons were made across seven pharmacokinetic (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and UGT2B15) and seven pharmacodynamic (BDNF, COMT, HLA-A, HTR2A, HTR2C, OPRM1, and SLC6A4) genes that were included on ≥2 of the four DST testing panels. Among these overlapping genes, genotype (33-100%) and predicted phenotype (20-100%) agreement varied substantially. Medication recommendation agreement was the greatest for mood stabilizers (84%), followed by antidepressants (56%), anxiolytics/hypnotics (56%), and antipsychotics (55%). Approximately one-quarter (26%) of all medication recommendations were jointly flagged by two or more DSTs as "actionable" but 19% of these recommendations provided conflicting advice (e.g., dosing) for the same medication.The level of disagreement in medication recommendations across the pharmacogenetic DSTs indicates that these tests cannot be assumed to be equivalent or interchangeable. Additional efforts to standardize genetic-based phenotyping and to develop medication guidelines are warranted.
在5名患有重度抑郁症且之前至少有两次抗抑郁药治疗失败的门诊患者中，对四种基于药物遗传学的商业决策支持工具（DST）之间的一致性程度进行了检查。对四种DST检测面板中≥2种所包含的7种药代动力学基因（CYP1A2、CYP2B6、CYP2C19、CYP2C9、CYP2D6、CYP3A4和UGT2B15）和7种药效学基因（BDNF、COMT、HLA - A、HTR2A、HTR2C、OPRM1和SLC6A4）进行了比较。在这些重叠基因中，基因型一致性（33% - 100%）和预测表型一致性（20% - 100%）差异很大。情绪稳定剂的用药推荐一致性最高（84%），其次是抗抑郁药（56%）、抗焦虑药/催眠药（56%）和抗精神病药（55%）。所有用药推荐中约四分之一（26%）被两种或更多DST共同标记为“可采取行动的”，但这些推荐中有19%针对同一药物提供了相互矛盾的建议（例如给药剂量）。药物遗传学DST之间用药推荐的不一致程度表明，不能认为这些检测是等效的或可互换的。有必要进一步努力规范基于基因的表型分析并制定用药指南。
