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

描述(申请人提供)：在美国，阿片类药物越来越多地被用于治疗慢性疼痛。美国老年医学会的一个特别小组在2009年发表了指南，建议将阿片类药物作为治疗中重度疼痛、疼痛相关损害和疼痛相关生活质量下降的一线药物。然而，延长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了患者治疗不到六个月的时间。相比之下，一些患者需要接受多年的阿片类药物治疗。阿片类药物治疗最令人担忧的安全风险，也是阿片类药物使用最直接的原因是处方阿片类药物过量。在医疗使用阿片类药物增加的同时，处方类阿片类药物过量的比率急剧上升。50岁至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一年龄段的前几代人相比，这一年龄段的人使用药物和与药物使用有关的不良后果的风险更高。因此，随着这一代人的老龄化和患上更多需要治疗的慢性疼痛症状，更多关于阿片类药物治疗在过量风险方面的安全性的数据至关重要。虽然在所有年龄的样本中，阿片类药物剂量已被确定为治疗慢性疼痛患者中阿片类药物过量死亡的预测因子，但尚未研究阿片类药物方案与处方阿片类药物过量风险的关系，特别是在老年人。此外，关于其他患者和治疗特征与处方阿片类药物过量风险的关系的数据有限。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CDC国家死亡指数中针对50岁及以上患有慢性疼痛的VHA患者的特定原因死亡数据。主要的具体目标将是：(1)检查阿片类药物方案(剂量和时间表)与接受阿片类药物的老年人中处方阿片类药物过量的关系；以及(2)确定具体的诊断(例如疼痛诊断、药物使用障碍和其他精神疾病、痴呆、慢性阻塞性肺病、心血管疾病和睡眠呼吸暂停)和治疗利用模式与接受阿片类药物的老年人中处方阿片类药物过量的风险如何相关。其他次级分析将在50岁至65岁之间的个体子集中检查这些关系。由于指示可能造成混淆，分析将包括多变量、边际结构模型和必要时的工具变量方法。拟议的研究结果可能对提高当代和未来几代老年人在慢性疼痛治疗中使用阿片类药物的安全性具有广泛的影响。 公共卫生相关性：阿片类止痛药的长期安全性尚不清楚，尽管这些药物用于治疗慢性疼痛变得越来越普遍。阿片类药物使用最令人担忧的安全风险是服药过量，老年人慢性疼痛和服药过量的风险尤其大。通过研究患者和治疗特征与老年人处方阿片类药物过量死亡风险的关系，这项研究将帮助慢性疼痛患者及其提供者做出与阿片类药物治疗相关的决定。

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. PUBLIC HEALTH RELEVANCE: The long-term safety of opioid pain medications is unknown, despite the use of these medications to treat chronic pain becoming increasingly common. The most concerning safety risk for opioid medication use is overdose, and older adults are particularly at risk for both chronic pain and overdose. By examining how patient and treatment characteristics relate to risk of prescription opioid overdose mortality among older adults, this research will assist patients with chronic pain and their providers in making opioid treatment-related decisions.