Prescription Opioid Analgesics and Risk of Major Depression

处方阿片类镇痛药与重度抑郁症的风险

• 批准号: 8700918
• 负责人: Jeffrey F. Scherrer
• 金额: $ 20.22万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700918
• 关键词: Accounting; Acute; Acute Pain; Adverse effects; Antidepressive Agents; Cessation of life; Characteristics; Chronic; Clinical Trials; Cohort Studies; Computerized Medical Record; Confounding Factors (Epidemiology); Control Groups; Cox Proportional Hazards Models; Data; Databases; Development; Diagnosis; Disease remission; Dose; Emotional; Epidemic; Equilibrium; Healthcare; Human; Lead; Link; Major Depressive Disorder; Measures; Mediation; Medical Records; Mental Depression; Methods; Modeling; Monitor; Morphine; National Institute of Mental Health; Opioid; Opioid Analgesics; Outcome; Outpatients; Overdose; Pain; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Prevalence; Probability; Public Health; Recording of previous events; Recurrence; Relapse; Relative (related person); Reporting; Research Domain Criteria; Residual state; Resistance; Risk; Sampling; Series; Signal Transduction; Substance Use Disorder; Survival Analysis; Symptoms; Testing; United States; United States Department of Veterans Affairs; Visit; Weight; Work; base; chronic depression; chronic pain; cohort; depressive symptoms; design; experience; human subject; novel; opioid abuse; patient population; prescription opioid; programs; prospective; public health relevance; treatment-resistant depression; vehicular accident

DESCRIPTION (provided by applicant): The purpose of this study is to determine the impact of prescription opioid analgesic use (OAU) on the risks of depression, depression relapse and treatment resistant depression (TRD). The study approach is designed to establish the strongest evidence that OAU causes these depression outcomes independent of the known association between chronic pain and depression. Opioid analgesics are the most frequently prescribed medication in the US and in each state, with the total number of prescriptions exceeding 130 million annually. This represents a 10-fold increase in OAU since 1990, a period during which the number of outpatient visits for conditions associated with chronic pain remained relatively stable. OAU has recognized adverse effects on physical and emotional functioning and our preliminary studies reveal patients using opioids for >180 days are at increased risk of depression, compared to those who use < 90 days. This effect remained evident even after controlling for the reason for which the drug is prescribed, i.e. chronic pain. Veterans Administration (VA) electronic medical record data spanning 14 years provides information to establish temporal precedence relative to OAU, depression, relapse and TRD and provides measures of relevant covariates. We will compare results in a demographically distinct, nationally representative data base from a cohort of privately insured enrollees in United Healthcare (UHC). In each data base we will test hypotheses after correcting for the OAU- pain-depression confound by using instrumental variable methods to control for unmeasured confounding and propensity scores to balance the distribution of covariates across duration and dose of OAU. Cox proportional hazard models will then be computed and will account for the persistence of pain to demonstrate chronic OAU independently leads to new episode depression, relapse and TRD. Analysis will begin by creating a cohort of 500,000 unique VA patients with medical record data from 1999-2012. For the first aim, the cohort of patients will be free of depression and free of OAU for two years prior to baseline (2001). In this cohort we will determine the OAU duration and dose associated with increased risk of a new episode of depression. For aim 2, the cohort of patients will be free of OAU for two years and have a diagnosis of depression in the year prior to baseline. In this cohort we will determine whether OAU duration and dose increases the risk of relapse in patients who experience a period of remission and contributes to TRD. For aim 3, we will determine if findings differ in a non-VA patient population and, if so, identify patient characteristics that explain differences. Results wll have an immediate impact on determining the previously unmeasured public health burden of depression, relapse and TRD that may be occurring due to an exponential increase in opioid prescribing in the United States. This R21 will lead to a prospective cohort study to characterize lifetime depression histories and symptom level change in OAU associated depression and culminate in clinical trials of antidepressant therapy to reduce risk of depression for patients requiring opioid analgesics.

描述（由申请人提供）：本研究的目的是确定处方阿片类镇痛药（OAU）对抑郁症、抑郁症复发和治疗难治性抑郁症（TRD）风险的影响。该研究方法旨在建立最有力的证据，证明非统组织导致这些抑郁结果独立于慢性疼痛和抑郁之间的已知关联。阿片类镇痛药是美国和各州最常用的处方药，每年的处方总数超过1.3亿。这代表非统组织自1990年以来增加了10倍，在此期间，与慢性疼痛有关的门诊次数保持相对稳定。非统组织已经认识到对身体和情绪功能的不利影响，我们的初步研究表明，与使用< 90天的患者相比，使用阿片类药物180天的患者患抑郁症的风险增加。即使在控制了药物的处方原因（即慢性疼痛）之后，这种效果仍然明显。退伍军人管理局（VA）跨越14年的电子病历数据提供了有关非统组织、抑郁、复发和TRD的时间优先权的信息，并提供了相关协变量的度量。我们将比较结果在人口统计学上不同的，具有全国代表性的数据库，从一个队列的私人保险登记在联合医疗（UHC）。在每个数据库中，我们将通过使用工具变量方法来控制未测量的混淆和倾向分数，以平衡非统持续时间和剂量间协变量的分布，在校正非统-疼痛-抑郁混淆后检验假设。然后将计算Cox比例风险模型，并将考虑疼痛的持续性，以证明慢性非统组织独立导致新发作的抑郁，复发和TRD。分析将首先创建一个由50万名独特的退伍军人事务部患者组成的队列，这些患者拥有1999年至2012年的医疗记录数据。对于第一个目标，患者队列将是