Trajectory of Adverse events and Analgesia with Opioids in older adults - TAANGO

描述（由申请人提供）：老年人疼痛的药物治疗通常包括阿片类药物，这是最近专家指南中推荐的。阿片类药物在控制急性疼痛方面是有效的，但在绝症和姑息治疗方面可能没有得到充分利用。然而，慢性非癌性疼痛的最佳治疗方法仍然存在争议，因为关于长期使用阿片类药物的镇痛轨迹或不良反应的数据很少。最近的研究强调了一些长期不良事件，包括过量用药风险、性腺功能减退、跌倒和骨折，以及神经心理影响，如认知障碍、抑郁、睡眠障碍和性功能障碍。对于其中的大多数，阿片类药物的患病率、时间过程和因果作用（相对于慢性疼痛或合并症）仍不清楚。我们的最终目标是对俄勒冈州农村地区阿片类药物的处方模式、镇痛效果和不良反应进行前瞻性研究，招募在阿片类药物起始治疗前患有慢性疼痛的患者。在开始这样的队列研究之前，我们建议进行试点，以确定研究程序的可行性，估计阿片类药物长期起始的发生率，并估计选定药物效应的发生率。试点研究将在俄勒冈农村实践研究网络进行。目标人群是55岁以上患有慢性肌肉骨骼疼痛的成年人。具体目的是：(1)证明我们可以从农村实践中招募足够数量的目标患者，并获得高的研究措施随访率；(2)估计目标人群中开始阿片类药物治疗的比率，以及长期使用阿片类药物的初步预测因素（如疼痛严重程度、合并症、既往阿片类药物治疗、使用其他受控物质、吸烟和情绪障碍）；(3)确定在阿片类药物治疗前和开始长期阿片类药物治疗后一年开始的镇痛和神经心理不良反应（抑郁、应用认知、疲劳、睡眠障碍、性功能障碍）的轨迹。我们假设最初的镇痛效果随着药物耐受性的发生而减弱，但随着剂量的增加而恢复。我们还假设阿片类药物与新的或加重的神经心理事件有关，这些事件随着治疗时间的延长而增加。

DESCRIPTION (provided by applicant): Pharmacotherapy for pain in older adults often includes opioids, which are recommended in recent expert guidelines. Opioids are effective in managing acute pain and may have been underused for terminal illness and palliative care. However, the optimal approach to therapy for chronic non-cancer pain remains controversial because of sparse data on the trajectory of analgesia or adverse effects with long-term opioid use. Recent studies highlight several long-term adverse events, including overdose risk, hypogonadism, falls and fractures, and neuropsychological effects such as cognitive impairment, depression, sleep disturbance, and sexual dysfunction. For most of these, the prevalence, time course, and causal role of opioids (as opposed to chronic pain or comorbidity) remain unclear. Our ultimate goal is a prospective study of opioid prescribing patterns, analgesic effects, and adverse effects in rural Oregon, enrolling patients with chronic pain prior to opioid initiation. Before embarking on such a cohort study, we propose a pilot to establish the feasibility of research procedures, estimate the incidence of long-term opioid initiation, and estimate the incidence of selected drug effects.The pilot study will be conducted in the Oregon Rural Practice Research Network. The target population is adults over age 55 with chronic musculoskeletal pain. The Specific Aims are: (1) To demonstrate that we can enroll adequate numbers of target patients from rural practices and obtain high rates of follow up on study measures; (2) To estimate rates of initiating opioid therapy in our target population, and tentative predictors of long term use (such as pain severity, comorbidity, prior opioid therapy, use of other controlled substances, smoking, and mood disorders); and (3) To determine the trajectory of analgesia and neuropsychological adverse effects (depression, applied cognition, fatigue, sleep disturbance, sexual dysfunction) beginning prior to opioid therapy and during the year following initiation of long-term opioid therapy. We hypothesize that there is initial analgesc benefit that wanes as drug tolerance occurs, but resumes with dose increases. We also hypothesize that opioids will be associated with new or exacerbated neuropsychological events that increase with duration of therapy. PUBLIC HEALTH RELEVANCE: Chronic pain and painkiller use are common in older adults. Differences between young and old regarding physical and psychosocial responses to pain and opioid therapy require specific study in the elderly. Optimal care remains controversial, as efficacy of opioids for chonic pain remains uncertain, and side effects are increasingly recognized. New evidence will help doctors and patients to make better treatment choices.