Mayo Clinic Alix School of Medicine. 200 1st St SW, Rochester, MN, 55905, USA.
Mayo Clinic Department of Psychiatry and Psychology, 1216 2nd St SW, Rochester, MN, 55902, USA.
J Psychiatr Res. 2020 Jul;126:105-111. doi: 10.1016/j.jpsychires.2020.05.002. Epub 2020 May 10.
In psychiatric patients, medication adverse effects are regularly attributed to psychosomatic causes. However, many psychotropic medications are metabolized by cytochrome P450 (CYP450) enzymes. In the setting of polypharmacy, the activity of these enzymes may produce unfavorable drug-drug interactions (DDI) and drug-genotype interactions (DGI) that contribute to morbidity and mortality. This study sought to estimate the risk of adverse DDI and DGI in psychiatric inpatients with polypharmacy. We assessed whether medication changes made after pharmacogenetics (PGx) testing correlated with changes in side effects and overall improvement. Adult psychiatry inpatients with polypharmacy, defined as 5 or more scheduled prescription medications, completed the 24-item Antidepressant Side Effect Checklist (ASEC) questionnaire on enrollment and underwent PGx testing. Analysis of PGx results focused on whether the CYP2D6 and CYP2C19 phenotypes were "extreme," defined as poor, poor to intermediate, or ultrarapid. Approximately 30 days after PGx results were sent to outpatient providers, patients were contacted to obtain their current medication list and ASEC and Clinical Global Impression Improvement (CGI-I) scores. A total of 80 patients were enrolled, and 52 (65%) completed follow-up. ASEC scores improved from 11.5 (±8.1) to 7.2 (±6.0) (p = 0.0009). Mean CGI-I score was 2.7 (±1.4), between "minimal" to "much improved." However, linear regression revealed that these improvements were not correlated with whether medications were changed. We concluded that the impact of drug-genotype interactions in this small sample of inpatients with polypharmacy was low, and that patient improvement was related not to PGx-guided medication changes but to other treatments during hospitalization.
在精神科患者中，药物不良反应通常归因于心身原因。然而，许多精神药物是由细胞色素 P450（CYP450）酶代谢的。在多种药物治疗的情况下，这些酶的活性可能会产生不良的药物-药物相互作用（DDI）和药物-基因型相互作用（DGI），从而导致发病率和死亡率增加。本研究旨在评估患有多种药物治疗的精神科住院患者发生不良 DDI 和 DGI 的风险。我们评估了在进行药物遗传学（PGx）检测后进行药物调整是否与副作用和整体改善的变化相关。患有多种药物治疗的成年精神科住院患者，定义为服用 5 种或更多种规定的处方药，在入组时完成 24 项抗抑郁药副作用检查表（ASEC）问卷，并进行 PGx 检测。PGx 结果分析的重点是 CYP2D6 和 CYP2C19 表型是否为“极端”，定义为差、差到中等或超快代谢。在 PGx 结果发送给门诊医生大约 30 天后，联系患者以获取他们当前的药物清单和 ASEC 和临床总体印象改善（CGI-I）评分。共有 80 名患者入组，其中 52 名（65%）完成了随访。ASEC 评分从 11.5（±8.1）改善至 7.2（±6.0）（p=0.0009）。平均 CGI-I 评分为 2.7（±1.4），介于“轻微”到“明显改善”之间。然而，线性回归显示，这些改善与是否调整药物无关。我们的结论是，在这个患有多种药物治疗的小样本住院患者中，药物-基因型相互作用的影响较低，患者的改善与 PGx 指导下的药物调整无关，而是与住院期间的其他治疗有关。
