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

项目摘要 抑郁症的患病率和抑郁症的药物治疗都大约是 这些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， 研究表明与抗抑郁药使用相关的低血糖风险增加。一个潜在 解释这种关联的机制是抗抑郁药和抗抑郁药之间可能的药物相互作用（DDI）。 口服降糖药（OAD）。某些选择性5-羟色胺再摄取抑制剂（SSRI）抑制CYP 2C 9 酶，这是负责一些糖尿病药物的代谢。只有一项流行病学研究 已经发表了对这种潜在DDI的调查，并报告了不精确的结果。有必要 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。这项研究的目的是研究协同效应的潜在影响， 使用CYP 2C 9代谢的OAD和CYP 2C 9抑制性抗抑郁药对严重 低血糖，使用严格的研究设计方法和与低血糖相关的医疗保险索赔数据库， 电子健康记录（EHR）用于65岁或以上的患者人群，这些患者与 医疗保健系统。在目标1中，我们将确定合并使用OAD的患病率， 由CYP 2C 9酶代谢或抑制CYP 2C 9酶的抗抑郁药，并评估处方趋势 并估计伴随OAD和抗抑郁药使用与低血糖之间的相关性 使用有源比较器设计。在OAD使用者人群中，我们将比较 合并使用CYP 2C 9抑制性抗抑郁药与 接受被认为不与CYP 2C 9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代码识别严重低血糖结局 基于算法利用适当和可靠的研究设计方法，结合丰富的 医疗保健数据可以提供OAD-抗抑郁药相互作用之间潜在联系的证据， 严重低血糖这个问题特别重要，因为需要平衡适当治疗 低血糖的巨大负担。这项研究的结果将为临床护理提供信息， 糖尿病患者，并协助医疗保健提供者优化治疗流行的共病心理健康 条件从长远来看，这项工作将是急需的努力的一部分，以产生可靠的证据， 患者和供应商管理慢性疾病与复杂的药物治疗策略。

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.