Harvard South Shore Psychiatry Residency Training Program, Brockton, MA, USA; Department of Psychiatry, Veterans Affairs Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Harvard South Shore Psychiatry Residency Training Program, Brockton, MA, USA; Department of Psychiatry, Veterans Affairs Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Psychiatry Res. 2019 Jan;271:604-613. doi: 10.1016/j.psychres.2018.12.053. Epub 2018 Dec 8.
Treatment non-response and adverse reactions are common in patients receiving antidepressants. Personalizing psychiatric treatment based on pharmacogenetic testing has been proposed to help clinicians guide antidepressant selection and dosing. This systematic literature review assesses the two most robustly studied drug-metabolizing enzymes, CYP2D6 and CYP2C19, and examines whether obtaining CYP2D6 and CYP2C19 testing can be used to predict antidepressant response or adverse drug reactions in order to improve clinical outcomes. In general, literature reviews published prior to 2013 indicated that results have been inconsistent linking CYP2D6 and CYP2C19 to antidepressant treatment outcomes, suggesting that more evidence is required to support the clinical implementation of genotyping to predict outcomes. We thus performed an extensive and systematic literature review, focusing on studies published from 2013 through 2018. Sixteen studies were found to be relevant. The results yielded inconsistent findings, suggesting that CYP2D6 and CYP2C19 testing may predict response in certain individuals, but it remains unclear if this will translate to improved clinical outcomes. Further research is required to determine when pharmacogenetic testing should be utilized and in which populations it is indicated. Randomized, controlled, prospective trials with adequate sample sizes would best clarify whether genotype-guided antidepressant selection will ultimately improve clinical outcomes.
在接受抗抑郁药治疗的患者中，治疗无反应和不良反应很常见。基于药物遗传学检测来个性化精神科治疗，以帮助临床医生指导抗抑郁药的选择和剂量，已被提出。本系统文献综述评估了研究最充分的两种代谢酶，CYP2D6 和 CYP2C19，并探讨了获得 CYP2D6 和 CYP2C19 检测是否可用于预测抗抑郁药反应或药物不良反应，以改善临床结局。一般来说，2013 年之前发表的文献综述表明，将 CYP2D6 和 CYP2C19 与抗抑郁治疗结果联系起来的结果一直不一致，这表明需要更多的证据来支持基于基因分型预测结果的临床实施。因此，我们进行了广泛而系统的文献综述，重点关注 2013 年至 2018 年期间发表的研究。发现有 16 项研究相关。结果得出的结论不一致，表明 CYP2D6 和 CYP2C19 检测可能可以预测某些个体的反应，但尚不清楚这是否会转化为改善的临床结局。需要进一步的研究来确定何时应进行药物遗传学检测以及在哪些人群中进行检测。具有足够样本量的随机、对照、前瞻性试验将最能阐明基因型指导的抗抑郁药选择是否最终会改善临床结局。
