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

描述（由申请人提供）：阿片类药物已越来越多地用于治疗美国慢性疼痛。美国老年病学会的一个特别小组于2009年发布了指南，建议使用阿片类药物作为中重度疼痛、疼痛相关损害和疼痛相关老年人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仅监测了治疗不到6个月的患者。相比之下，一些患者接受阿片类药物治疗多年。阿片类药物治疗引起的最令人担忧的安全性风险，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，与处方类阿片有关的过量使用率也急剧增加。年龄在50至65岁之间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龄的前几代人相比，这个年龄段的人的物质使用和物质使用相关的不良后果增加。因此，关于阿片类药物治疗过量风险的安全性的更多数据至关重要，因为这一代人的年龄和发展需要更多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中阿片类药物过量死亡的预测因素，但尚未检查阿片类药物治疗方案与老年人处方阿片类药物过量风险的关系。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退伍军人健康管理局（VHA）2000 - 2008年记录的二次分析，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50岁及以上慢性疼痛VHA患者的特定原因死亡率数据。主要的具体目的是（1）检查阿片类药物治疗方案（剂量和时间表）与接受阿片类药物的老年人处方阿片类药物过量的相关性;以及（2）确定具体诊断（例如，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的老年人中处方阿片类药物过量的风险有关。额外的次要分析将在50至65岁的个体子集中检查这些关系。由于适应症的潜在混杂，分析将包括多变量、边际结构模型和工具变量方法（如需要）。拟议研究的结果可能对改善当前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，尽管使用这些药物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过量，老年人特别容易出现慢性疼痛和过量。通过研究患者和治疗特征如何与老年人处方阿片类药物过量死亡的风险相关，这项研究将帮助慢性疼痛患者及其提供者做出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.