Objective:

In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression.

Methods:

The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized.

Results:

Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results.

Conclusions:

The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response.

中文翻译：

---

治疗抑郁症的药物基因组学临床支持工具

 目的：

在这篇综述中，作者更新了美国精神病学协会生物标志物和新疗法研究工作组 2018 年的立场声明，关于药物基因组学 （PGx） 工具，用于抑郁症的治疗选择。

 方法：

对 2017 年至 2022 年发表的使用 PGx 工具选择抑郁症治疗选择的研究的新临床试验和荟萃分析的文献进行了综述。总结了盲法和控制条件，以及主要和次要结局和事后分析。

 结果：

确定了 11 项新的临床试验和 5 项荟萃分析;所有研究的主要结局指标均与治疗反应的速度或疗效有关。3 项试验 （27%） 对主要结局指标有效，具有统计学意义;这三项研究使用了不同的 PGx 工具;一项研究是开放标签的，另外两项是小型单盲试验。5 项试验 （45%） 未检测到对主要或次要结局指标具有统计学意义的疗效。只有一项试验 （9%） 将不良事件作为主要结局指标。所有研究都有明显的局限性;例如，没有一项研究采用完全盲法的研究设计，只有两项研究试图对治疗临床医生实施盲法，并且没有一项研究纳入了估计盲法有效性或缺乏盲法对研究结果影响的措施。

 结论：

这些新数据的添加并未改变 2018 年报告的建议或美国食品和药物管理局的建议，即证据不支持使用目前可用的组合 PGx 工具来选择重度抑郁症的治疗。未来研究的优先工作以及有效工具的开发和测试包括全盲研究设计、纳入目前未包含在任何市售测试中的有希望的遗传变异，以及研究药物基因组学的其他用途，例如估计罕见药物不良反应的可能性，而不是增加药物反应的速度或幅度。