Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Optum, Eden Prairie, Minnesota, USA.
J Child Adolesc Psychopharmacol. 2024 Feb;34(1):28-33. doi: 10.1089/cap.2023.0043.
Combinatorial pharmacogenetic testing panels are widely available in clinical practice and often separate medications into columns/bins associated with low, medium, or high probability of gene-drug interactions. The objective of the Adolescent Management of Depression (AMOD) study was to determine the clinical utility of combinatorial pharmacogenetic testing in a double-blind, randomized, controlled effectiveness study by comparing patients who had genetic testing results at time of medication initiation to those that did not have results until week 8. The objective of this analysis was to assess and report additional outcomes with respect to significant gene-drug interactions (i.e., a medication in the high probability gene-drug interaction bin as defined by a proprietary algorithm) compared with patients taking a medication with minimal to moderate gene-drug interactions (i.e., a medication from the low or medium probability gene-drug interaction bin, respectively). Adolescents 13-18 years ( = 170) with moderate to severe major depressive disorder received pharmacogenetic testing. Symptom improvement and side effects were assessed at baseline, week 4, week 8, and 6 months. Patients were grouped into three categories based on whether the medication they were prescribed was associated with low, medium, or high risk for gene-drug interactions. Patients taking a medication from the low/medium gene-drug interaction bin were compared with patients taking a medication from the high gene-drug interaction bin. Patients taking a medication from the high gene-drug interaction bin were more likely to endorse side effects compared with patients taking a medication in the low/medium gene-drug interaction bin at week 8 ( = 0.001) and 6 months ( < 0.0001). Depressive symptom severity scores did not differ significantly across the medication bins. This study demonstrates the utility of gene-drug interaction testing to guide medication decisions to minimize side effect burden rather than solely prioritizing the search for the most efficacious medication. (Clinical Trials Registration Identifier: NCT02286440).
组合式药物遗传学检测面板在临床实践中广泛应用，通常将药物分为与基因-药物相互作用低、中、高概率相关的列/框。青少年抑郁症管理（AMOD）研究的目的是通过比较开始用药时进行基因检测的患者与第 8 周后才获得检测结果的患者，确定组合式药物遗传学检测在双盲、随机、对照有效性研究中的临床实用性。本分析的目的是评估和报告与显著基因-药物相互作用（即根据专有算法定义的高概率基因-药物相互作用框中的药物）相比，具有最小至中度基因-药物相互作用的药物（即低或中概率基因-药物相互作用框中的药物）的附加结果。13-18 岁（ = 170）患有中度至重度重度抑郁症的青少年接受了药物遗传学检测。在基线、第 4 周、第 8 周和 6 个月时评估症状改善和副作用。根据他们开的药物是否与基因-药物相互作用的低、中或高风险相关，患者被分为三组。与服用低/中基因-药物相互作用框药物的患者相比，服用高基因-药物相互作用框药物的患者在第 8 周（ = 0.001）和 6 个月（ < 0.0001）时更有可能出现副作用。在药物框中，抑郁症状严重程度评分没有显著差异。本研究表明，基因-药物相互作用检测可用于指导药物决策，以最大限度地降低副作用负担，而不仅仅是优先寻找最有效的药物。（临床试验注册标识符：NCT02286440）。
