Mental Health Service, VA San Diego Healthcare System, San Diego, CA, USA.
Department of Psychiatry, UC San Diego, La Jolla, CA, USA.
J Psychopharmacol. 2021 Aug;35(8):992-1002. doi: 10.1177/02698811211015224. Epub 2021 May 3.
Pharmacotherapies for depression are often ineffective and treatment-resistant depression (TRD) is common across bipolar disorder (BD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Patient genetic information can be used to predict treatment outcomes. Prospective studies indicate that pharmacogenetic (PGX) tests have utility in the treatment of depression. However, few studies have examined the utility of PGX in other diagnoses typified by depression, or in veterans, a cohort with high rates of medical comorbidity, social stress, and suicide.
To determine the efficacy of genetically guided pharmacological treatment of TRD.
We conducted an 8-week, prospective, multisite, single-blind study in 182 veterans with TRD including patients with BD, MDD, and PTSD. Subjects were randomly assigned to PGX-guided treatment in which the clinician incorporated PGX information into decision-making, or treatment as usual (TAU).
Overall, the PGX group improved marginally faster compared to TAU, but the difference was not statistically significant. Secondary analyses revealed that only PTSD patients showed a potential benefit from PGX testing. Patients predicted by PGX testing to have moderate levels of genetic risk showed a significant benefit from the PGX-guided treatment, whereas other risk groups demonstrated no benefit. Clinicians generally found the PGX test was useful, particularly in more depressed patients and/or those with more warnings for significant or serious adverse outcomes. Clinicians more often used the results to select a drug, but only rarely to adjust dosing.
The data reveal possible group differences in the utility of PGX testing in veterans with TRD.ClinicalTrials.gov Identifier: NCT04469322.
抗抑郁药物治疗往往无效，且治疗抵抗性抑郁症（TRD）在双相情感障碍（BD）、重度抑郁症（MDD）和创伤后应激障碍（PTSD）中都很常见。患者的遗传信息可用于预测治疗结果。前瞻性研究表明，药物遗传学（PGX）测试在抑郁症的治疗中有一定作用。然而，很少有研究在其他以抑郁为特征的诊断中或在退伍军人中检验 PGX 的作用，而退伍军人这一群体存在较高的医疗合并症、社会压力和自杀率。
确定基因指导的 TRD 药物治疗的疗效。
我们对 182 名 TRD 退伍军人进行了为期 8 周的前瞻性、多地点、单盲研究，包括患有 BD、MDD 和 PTSD 的患者。受试者被随机分配到 PGX 指导治疗组，即临床医生将 PGX 信息纳入决策中，或采用常规治疗（TAU）。
总体而言，PGX 组的改善速度略快于 TAU 组，但差异无统计学意义。进一步分析显示，只有 PTSD 患者可能从 PGX 测试中获益。PGX 测试预测为中度遗传风险的患者从 PGX 指导治疗中获益显著，而其他风险组则未获益。临床医生普遍认为 PGX 测试有用，特别是在更抑郁的患者和/或那些有更多严重不良事件警告的患者中。临床医生更多地使用结果来选择药物，但很少调整剂量。
数据显示，PGX 测试在 TRD 退伍军人中的作用可能存在群体差异。
NCT04469322。
