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：

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治疗抑郁症的药物基因组学临床支持工具

客观的：

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型治疗委员会研究工作组 2018 年关于抑郁症治疗选择的药物基因组 (PGx) 工具的立场声明。

方法：

我们对 2017 年至 2022 年发表的新临床试验和荟萃分析文献进行了回顾，这些研究使用 PGx 工具选择抑郁症的治疗方法。总结了盲法和控制条件，以及主要和次要结果以及事后分析。

结果：

确定了十一项新的临床试验和五项荟萃分析；所有研究的主要结果指标均与治疗反应的速度或功效相关。三项试验（27%）证明了主要结局指标的有效性具有统计学意义；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。五项试验（45%）未检测到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%）使用不良事件作为主要结局指标。所有研究都有显着的局限性；例如，没有一项研究采用完全盲法研究设计，只有两项研究试图对治疗临床医生进行盲法，并且没有一项研究采取措施来估计盲法的有效性或缺乏盲法对研究结果的影响。

结论：

这些新数据的添加并没有改变 2018 年报告的建议，也没有改变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方法。未来研究以及有效工具的开发和测试的优先工作包括完全盲法研究设计、纳入目前未包含在任何商业测试中的有希望的遗传变异，以及药物基因组学其他用途的调查，例如估计罕见不良药物的可能性效果，而不是增加药物反应的速度或程度。