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

• 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
• 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

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.

项目摘要 抑郁症的患病率和抑郁症的药理治疗均约为 在非糖尿病人群中的患病率。但是，病例报告，动物研究和流行病学 研究表明，与使用抗抑郁药有关的低血糖风险增加。一个潜力 解释这种关联的机制是抗抑郁药与 口服抗糖尿病药（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代谢。只有一项流行病学研究 研究了该潜在的DDI已发表并报告了不精确的结果。需要 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的含义。拟议的研究的目的是检查共同的潜在影响 利用CYP2C9-METEPOL的OAD和CYP2C9抑制抗抑郁药的风险 低血糖，使用严格的研究设计方法和与Medicare索赔数据库有关 与65岁以上的患者人群相互作用的电子健康记录（EHRS） UNC医疗保健系统。在AIM 1中，我们将确定伴随使用OAD的流行率 由CYP2C9酶代谢或抑制并评估处方趋势的抗抑郁药 随着时间的流逝，估计伴随OAD与抗抑郁药的关联与低血糖之间的关联 使用主动比较器设计。在OAD使用者中，我们将比较 那些同时接受CYP2C9抑制抗抑郁药的人与那些人之间的低血糖 接收不认为与CYP2C9相互作用的抗抑郁药。在AIM 2中，我们将验证一种算法 使用现有的ICD-9-CM映射的ICD-10-CM代码确定结果严重低血糖症 基于算法。利用适当可靠的研究设计方法与富富集 医疗保健数据可以提供有关OAD-抗抑制剂相互作用与 严重的低血糖。鉴于需要平衡足够的治疗方法，这个问题尤其重要 心理健康，低血糖负担。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的普遍性心理健康 状况。从长远来看，这项工作将是为生成可靠证据的急需的一部分 患者和提供者通过复杂的药理治疗策略管理慢性病。