A Feasibility and Pilot Study of Combined Treatment Protocol using Aerobic Exercise and Duloxetine in Older Adults with Symptomatic Knee Osteoarthritis and Comorbid Depression

症状性膝关节骨关节炎（OA）影响10%的男性和13%的60岁或以上的女性， 抑郁症状很常见，估计在这些患者中有五分之一的人中普遍存在。抑郁 症状使膝关节骨性关节炎疾病的严重程度恶化，并且是疼痛管理和参与的障碍 体力活动。临床护理指南建议对患有膝关节OA的老年人进行抑郁治疗， 没有提供如何同时管理这两种情况的指导，患者往往没有得到治疗， 他们的抑郁症状，并接受干预，只有他们的慢性身体疾病。这个问题 由于对患有慢性躯体疾病和共病抑郁症的个体的常规排除， 临床试验和缺乏为这些患者设计的方案。最近的研究提倡使用 同时有益于两种疾病的治疗，或使用两种干预措施的联合治疗， 设计为协同工作的平行模式，从而使方法的功效超出个人的功效 单一疾病靶点治疗。治疗指南建议通过锻炼来控制疼痛， 残疾和改善膝关节OA患者的心理社会健康，但遵守体力活动方案 在慢性疼痛和残疾患者中的发病率较低，并且只会因共病抑郁症而变得更糟。粘附 对于使用运动训练治疗抑郁症的疗效至关重要，并且没有这样的运动计划 曾经被设计用于并在伴有抑郁症状的OA患者中进行测试， 合规度洛沙汀是唯一一种适用于膝关节OA疼痛管理的抗抑郁药物 在治疗老年人抑郁症时已证明有效性和耐受性的患者，因此， 是运动训练的一种可行的药理学补充。没有联合收割机治疗方案 使用影响膝关节OA和抑郁症症状的干预措施，以及一种专注于共同治疗的策略， 这两种情况的管理可以传播给全科医生， 从业者因此，本K01应用程序的研究目标是评估可行性，然后进行试点测试， 方案包括有氧运动训练加度洛沙坦治疗症状性膝关节OA， 共病抑郁症拟议的研究将实施一段时间的密切指导和职业生涯 发展活动的重点是学习1）定性数据收集和分析的方法， 用于了解患者的观点和经验，2）实施策略， 评估临床研究中的干预措施。该提案与NIA战略方向保持一致， 老龄化研究强调老年人与多种慢性疾病，复杂的临床护理和 旨在引导一个研究项目，使用观察流行病学评估 和机制之间的肌肉骨骼疾病和共病抑郁症的老年人，以告知 制定旨在管理原发病和后遗症症状的方案。

Symptomatic knee osteoarthritis (OA) affects 10% of men and 13% of women 60 years or older, and depressive symptoms are common, estimated to be prevalent in one-fifth of these patients. Depressive symptoms worsen knee OA disease severity and are a barrier to pain management and engagement in physical activity. Clinical care guidelines recommend depression treatment in older adults with knee OA but provide no direction on how to simultaneously manage both conditions, and patients are often not treated for their depressive symptoms and receive interventions only for their chronic physical illness. This issue is exacerbated by the routine exclusion of individuals with chronic physical diseases and comorbid depression from clinical trials and lack of protocols designed for these patients. Recent research advocates the use of treatments that benefit both conditions simultaneously, or combined treatment using two interventions in parallel that are designed to work together, such that approaches enhance efficacy beyond that of an individual therapy with a single disease target. Treatment guidelines advise exercise programs to manage pain and disability and improve psychosocial health in those with knee OA, but compliance to physical activity protocols is low in persons with chronic pain and disability and is only made worse by comorbid depression. Adherence is critical to the efficacy of depression treatments using exercise training, and no such exercise program has ever been designed for and tested in OA patients with co-occurring depressive symptoms in a way to enhance compliance. Duloxetine is the only antidepressant medication indicated for pain management in knee OA patients that has demonstrated efficacy and tolerability when treating depression in older adults, and therefore, is a viable pharmacological complement to exercise training. There are no protocols that combine treatments using interventions that affect symptoms of both knee OA and depression, and a strategy focused on co- management of the two conditions could be disseminated to and implemented by generalist medical practitioners. Thus, the research goal of this K01 application is to evaluate the feasibility of and then pilot test a protocol comprised of aerobic exercise training plus duloxetine for the treatment of symptomatic knee OA and comorbid depression. The proposed research will be implemented with a period of close mentoring and career development activities focused on learning 1) methods for qualitative data collection and analysis that can be used to understand patients’ perspectives and experiences and 2) strategies for the implementation and evaluation of interventions in clinical research. This proposal is aligned with the NIA Strategic Directions for Research on Aging emphasizing older adults with multiple chronic conditions that complicate clinical care and is intended to lead to a research program that uses observational epidemiology evaluating the relationships and mechanisms between musculoskeletal disorders and comorbid depression in older adults to inform the development of protocols that are designed to manage symptoms of both the primary condition and sequalae.