Concomitant use of antidepressants and oral antidiabetic drugs and the risk of hypoglycemia

项目总结 抑郁症的患病率和抑郁症的药物治疗都大约是 这些疾病在非糖尿病人群中的患病率。然而，病例报告、动物研究和流行病学 研究表明，使用抗抑郁药会增加低血糖的风险。一种潜力 解释这种联系的机制可能是抗抑郁药物和药物之间的药物相互作用(DDiS) 口服抗糖尿病药物(OADs)。某些选择性5-羟色胺再摄取抑制剂(SSRI)抑制CYP2C9 酶，负责某些糖尿病药物的新陈代谢。只有一项流行病学研究 对这一潜在DDI的调查已经发表，但报告的结果并不准确。有必要 由精心设计的研究产生的证据，特别是在美国人群中，以更好地了解临床 这一潜在的DDI的影响。这项拟议的研究的目标是检查联合治疗的潜在影响。 应用CYP2C9代谢的OADs及其抑制药物治疗严重抑郁的风险 低血糖，使用严格的研究设计方法和与以下相关的医疗保险索赔数据库 65岁或以上患者的电子健康记录(EHR) 北卡罗来纳大学医疗保健系统。在目标1中，我们将确定同时使用OAD和OAD的流行率 由CYP2C9酶代谢或抑制CYP2C9酶的抗抑郁药，并评估处方趋势 随着时间的推移，并估计伴随的OAD与抗抑郁药的使用和低血糖之间的关联 采用有源比较器设计。在服用OAD的人群中，我们将比较 同时服用CYP2C9抑制类抗抑郁药的患者与服用抗抑郁药的患者之间的低血糖 服用被认为不会与细胞色素P450受体C9相互作用的抗抑郁药。在目标2中，我们将验证一个算法 使用从现有ICD-9-CM映射的ICD-10-CM编码识别严重低血糖的结果 基于算法的。利用适当可靠的研究设计方法与RICH相结合 医疗保健数据可以为OAD-抗抑郁药相互作用和 严重低血糖。这个问题尤其重要，因为需要平衡适当的治疗 精神健康和巨大的低血糖负担。这项研究的结果将为临床治疗提供参考 糖尿病患者，并协助医疗保健提供者优化普遍存在的并存心理健康的治疗 条件。从长远来看，这项工作将是迫切需要的努力的一部分，以便为 通过复杂的药物治疗策略管理慢性病的患者和提供者。

PROJECT SUMMARY The prevalence of depression and pharmacologic treatments for depression are both approximately twice the prevalence of these in non-diabetic populations. However, case reports, animal studies, and epidemiologic studies have suggested an increased risk of hypoglycemia associated with antidepressant use. One potential mechanism explaining this association is possible drug-drug interactions (DDIs) between antidepressants and oral antidiabetic drugs (OADs). Certain selective serotonin reuptake inhibitors (SSRIs) inhibit the CYP2C9 enzyme, which is responsible for the metabolism of some diabetes medications. Only one epidemiologic study investigating this potential DDI has been published and reported imprecise results. There is a need for evidence generated by well-designed studies, particularly in U.S. populations to better understand the clinical implications of this potential DDI. The goal of the proposed research is to examine the potential effect of co- utilization of CYP2C9-metabolized OADs and CYP2C9-inhibiting antidepressants on the risk of serious hypoglycemia, using rigorous study design approaches and a database of Medicare claims linked with electronic health records (EHRs) for a population of patients 65 years or older who have interacted with the UNC healthcare system. In Aim 1, we will determine the prevalence of concomitant use of OADs and antidepressants that are either metabolized by or inhibit the CYP2C9 enzyme and evaluate prescribing trends over time and estimate the association between concomitant OAD and antidepressant use and hypoglycemia using an active comparator design. Among a population of OAD users, we will compare the risk of hypoglycemia between those who concomitantly receive CYP2C9 inhibiting antidepressants and those who receive antidepressants that are not thought to interact with CYP2C9. In Aim 2, we will validate an algorithm for identifying the outcome severe hypoglycemia using ICD-10-CM codes mapped from an existing ICD-9-CM based algorithm. Leveraging appropriate and reliable study-design approaches in combination with rich healthcare data can provide evidence on the potential link between OAD-antidepressant interactions and severe hypoglycemia. This question is especially important, given the need to balance adequate treatment of mental health with the immense burden of hypoglycemia. The results from this study will inform clinical care for diabetes patients and assist healthcare providers in optimizing treatment for prevalent comorbid mental health conditions. In the long-term, this work will be a part of the much-needed effort to generate reliable evidence for patients and providers managing chronic conditions with complex pharmacologic treatment strategies.