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

抗抑郁药和口服抗糖尿病药的同时使用和低血糖的风险

基本信息

批准号：
10526807
负责人：
Sara Z. Dejene
金额：
$ 6.91万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10526807
关键词：
Adult Affect Age Algorithms American Animals Antidepressive Agents Antidiabetic Drugs Behavior Body mass index CYP2C9 gene Case Study Chronic Clinical Code Complex Data Databases Diabetes Mellitus Drug Interactions Drug usage Drug user Economic Burden Effectiveness Elderly Electronic Health Record Elements Emergency department visit Enrollment Enzymes Equilibrium Goals Gold Health Personnel Health system Healthcare Healthcare Systems Hospitalization Hypoglycemia ICD-10-CM ICD-9 ICD-9-CM Individual International Classification of Diseases International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10)Lead Link Maps Medical Care Costs Medicare Medicare claim Mental Depression Mental Health Metabolic Metabolism Methods Modification Non-Insulin-Dependent Diabetes Mellitus Oral Outcome Patient Care Patients Performance Pharmaceutical Preparations Pharmacoepidemiology Pharmacological Treatment Population Prevalence Provider Publishing Reporting Research Research Design Risk Sampling Selective Serotonin Reuptake Inhibitor Self Care Smoking Sulfonylurea Compounds Time trend United States Validation Work active comparator base beneficiary clinical care comorbidity design epidemiology study glycemic control improved insurance claims nateglinide non-diabetic outpatient programs patient population population health randomized trial treatment optimization treatment strategy

项目摘要

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.

项目概要抑郁症的患病率和抑郁症的药物治疗均约为两倍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，使用抗抑郁药物会增加低血糖的风险。一种潜力解释这种关联的机制是抗抑郁药和药物之间可能存在药物相互作用（DDI）口服抗糖尿病药（OAD）。某些选择性血清素再摄取抑制剂 (SSRI) 会抑制 CYP2C9 酶，负责某些糖尿病药物的代谢。只有一项流行病学研究对这一潜在 DDI 的调查已经发表，但报告的结果不准确。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种潜在 DDI 的影响。拟议研究的目的是检查共同的潜在影响使用 CYP2C9 代谢的 OAD 和 CYP2C9 抑制抗抑郁药对严重抑郁症风险的影响低血糖，使用严格的研究设计方法和与相关的医疗保险索赔数据库与 65 岁或以上有过互动的患者群体的电子健康记录 (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 和通过 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 和抗抑郁药物的使用与低血糖之间的关联使用有源比较器设计。在 OAD 用户群体中，我们将比较以下风险：同时接受 CYP2C9 抑制抗抑郁药和接受不被认为与 CYP2C9 相互作用的抗抑郁药物。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的结果基于算法。利用适当且可靠的研究设计方法并结合丰富的医疗保健数据可以提供 OAD 与抗抑郁药物之间的潜在联系和严重低血糖。鉴于需要平衡适当的治疗，这个问题尤其重要。心理健康与低血糖的巨大负担。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常见共病心理健康的治疗状况。从长远来看，这项工作将成为急需的努力的一部分，以产生可靠的证据使用复杂的药物治疗策略来管理慢性病的患者和提供者。