Prescription Opioid Analgesics and Risk of Major Depression

描述(申请人提供)：这项研究的目的是确定处方阿片类止痛剂(非统)的使用对抑郁症、抑郁症复发和难治性抑郁症(TRD)风险的影响。研究方法的目的是建立最有力的证据，证明非统组织导致这些抑郁结果，而与慢性疼痛和抑郁之间的已知联系无关。阿片类止痛药是美国和各州最常用的处方药物，每年的处方总数超过1.3亿张。这表明非统组织自1990年以来增加了10倍，在此期间，因慢性疼痛而就诊的门诊量保持相对稳定。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更高。即使在控制了开药的原因，即慢性疼痛之后，这种效果仍然很明显。退伍军人管理局(退伍军人管理局)14年来的电子病历数据提供了信息，以确定相对于非统组织、抑郁症、复发和TRD的时间顺序，并提供了相关协变量的衡量标准。我们将比较人口统计学上不同的、具有全国代表性的数据库中来自联合医疗(UHC)的一组私人保险参与者的结果。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杂分数和倾向分数，以平衡各协变量在非统组织持续时间和剂量上的分布，在纠正非统组织混淆的疼痛-抑郁之后检验假设。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地导致新的发作抑郁、复发和TRD。分析将首先创建一个由500,000名独特的VA患者组成的队列，其中包含1999-2012年的医疗记录数据。对于第一个目标，患者队列将是 在基线(2001年)之前的两年内没有抑郁，也没有非统组织。在这一组中，我们将确定非统组织的持续时间和剂量与新的抑郁症发作风险增加有关。对于目标2，这批患者将在两年内不再接受非统组织的治疗，并在基线前一年被诊断为抑郁症。在这个队列中，我们将确定非统组织的持续时间和剂量是否会增加缓解期患者复发的风险，并有助于TRD。对于目标3，我们将确定在非VA患者群体中发现的结果是否不同，如果是，确定解释差异的患者特征。结果将对确定以前未测量的抑郁、复发和TRD的公共健康负担产生直接影响，这些负担可能是由于美国阿片类药物处方的指数增长而发生的。这项R21将导致一项前瞻性的队列研究，以确定非统组织相关性抑郁症的终生抑郁史和症状水平变化的特征，并最终实现抗抑郁治疗的临床试验，以降低需要阿片类镇痛剂的患者的抑郁风险。

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.