Safety of Opioids for Older Adults: Determinants of Opioid Overdose Risk

描述（由申请人提供）：阿片类药物在美国越来越多地用于治疗慢性疼痛。美国老年医学会的一个特别小组在2009年发布了指南，建议使用阿片类药物作为老年人中度至重度疼痛、疼痛相关损伤和疼痛相关生活质量下降的一线治疗。然而，长期阿片类药物治疗慢性疼痛的安全性尚不清楚；大多数阿片类药物治疗慢性疼痛的随机对照试验只监测患者治疗时间少于6个月。相比之下，一些患者接受阿片类药物治疗多年。阿片类药物治疗最令人担忧的安全风险，也是最直接归因于阿片类药物使用的风险，是处方阿片类药物过量。在类阿片医疗使用增加的同时，与类阿片有关的处方过量服用率也急剧上升。50至65岁的成年人意外和故意过量死亡的风险特别高，与65岁以上的成年人以及同年龄段的前几代人相比，这个年龄段的人使用药物和药物使用相关的不良后果都有所增加。因此，更多关于阿片类药物治疗安全性的数据对于过量风险至关重要，因为这一代人年龄越来越大，需要更多的药物治疗的慢性疼痛状况。虽然阿片类药物剂量已被确定为所有年龄样本中接受慢性疼痛治疗的患者阿片类药物过量死亡的预测因子，但尚未对阿片类药物治疗方案与处方阿片类药物过量风险的关系进行研究，特别是针对老年人。此外，关于其他患者和治疗特征如何与处方阿片类药物过量风险相关的数据有限。拟议的病例队列研究将包括对2000-2008年退伍军人健康管理局（VHA）记录的二次分析，包括药房记录，门诊和住院治疗记录，以及疾病预防控制中心国家死亡指数中针对50岁及以上患有慢性疼痛的VHA患者的病因特异性死亡率数据。主要的具体目标将是：(1)在接受阿片类药物治疗的老年人中，检查阿片类药物治疗方案（剂量和时间表）与处方阿片类药物过量的关系；(2)确定特定诊断（如疼痛诊断、物质使用障碍和其他精神疾病、痴呆、COPD、CVD和睡眠呼吸暂停）和治疗利用模式与接受阿片类药物治疗的老年人处方阿片类药物过量风险之间的关系。额外的二次分析将在50至65岁的人群中检验这些关系。由于潜在的由指示混淆，分析将包括多变量，边际结构模型，并在需要时工具变量方法。拟议研究的结果可能对提高当前和未来几代老年人使用阿片类药物治疗慢性疼痛的安全性具有广泛的意义。

DESCRIPTION (provided by applicant): Opioid medications have been increasingly used in the treatment of chronic pain in the U.S. A special panel for the American Geriatrics Society published guidelines in 2009 that recommended using opioids as a first line treatment of moderate to severe pain, pain-related impairment, and pain-related diminished quality of life for older adults. However, the safety of extended opioid therapy for chronic pain is unknown; most randomized controlled trials of opioid therapy for chronic pain have only monitored patients for less than six months of treatment. In contrast, some patients are treated with opioids for years. The most concerning safety risk due to opioid therapy, and the most directly attributable to opioid use, is prescription opioid overdose. Parallel to the increase in the medical use of opioids the rate of prescription opioid-related overdoses has increased sharply. Adults between the ages of 50 and 65 are at particularly elevated risk for unintentional and intentional overdose death, and individuals in this age range have elevated substance use and substance use-related adverse outcomes compared to adults age 65+ as well as prior generations during the same ages. Consequently, more data on the safety of opioid therapy in regards to overdose risk is crucial as this generation ages and develops chronic pain conditions requiring medical treatment in greater numbers. While opioid dose has been established as a predictor of opioid overdose death among patients treated for chronic pain in all-age samples, opioid regimen has not been examined in relation to prescription opioid overdose risk specifically for older adults. Additionally, there are limited data on how other patient and treatment characteristics relate to prescription opioid overdose risk. The proposed case-cohort study will be comprised of secondary analysis of Veterans Health Administration (VHA) records for 2000-2008, including pharmacy records, outpatient and inpatient treatment records, and cause-specific mortality data from the CDC's National Death Index, for VHA patients age 50 and older with chronic pain. The primary specific aims will be to (1) examine the association of opioid regimen (dose and schedule) with prescription opioid overdose among older adults receiving opioids; and (2) to determine how specific diagnoses (e.g., pain diagnoses, substance use disorders and other psychiatric conditions, dementia, COPD, CVD, and sleep apnea) and treatment utilization patterns relate to risk of prescription opioid overdose among older adults receiving opioids. Additional secondary analyses will examine these relationships in the subset of individuals between the ages of 50 and 65. Because of the potential for confounding by indication, analyses will include multivariable, marginal structural models, and instrumental variable approaches when needed. The findings of the proposed study are likely to have broad implications for improving the safety of the use of opioids in chronic pain treatment for current and future generations of older adults.