Efficacy of Antidepressants in Chronic Back Pain

抗抑郁药治疗慢性背痛的疗效

• 批准号: 7794121
• 负责人: JOSEPH H ATKINSON
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7794121
• 关键词: Absence of pain sensation; Acute Pain; Address; Adverse effects; Affect; Aftercare; Analgesics; Anti-Inflammatory Agents; Anti-inflammatory; Antidepressive Agents; Back; Back Pain; Behavior Therapy; Chronic; Chronic Obstructive Airway Disease; Chronic low back pain; Clinic; Clinical; Clinical Trials; Clinical Trials Design; Cognitive Therapy; Combination Drug Therapy; Combined Modality Therapy; Controlled Clinical Trials; Coronary Arteriosclerosis; Cytochrome P450; Cytochromes; Descriptor Differential Scale; Desipramine; Diabetes Mellitus; Disease; Dose; Exercise; General Population; Genetic Polymorphism; Gulf War; Health; Healthcare; Hypertension; Individual; Intervention; Life; Major Depressive Disorder; Mediating; Medical; Medicine; Mental Depression; Meta-Analysis; Migraine; Modality; Modeling; Mood Disorders; Operative Surgical Procedures; Opioid; Outcome; Pain; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physicians; Placebos; Population; Prevalence; Primary Care Physician; Primary Health Care; Provider; Quality of life; Questionnaires; Randomized Clinical Trials; Relative (related person); Reporting; Research; Resistance; Safety; Solid; Staging; Substance Use Disorder; Syndrome; Testing; Therapeutic; Time; Tricyclic Antidepressive Agents; Variant; Veterans; Woman; aged; approach behavior; arm; arthropathies; authority; chronic back pain; chronic pain; cohort; cost; daily functioning; design; disability; drug clearance; effective therapy; effectiveness trial; efficacy trial; evidence base; expectation; falls; follow-up; improved; improved functioning; men; noradrenergic; painful neuropathy; primary outcome; public health relevance; randomized trial; secondary outcome; trial comparing

DESCRIPTION (provided by applicant): Project Summary Chronic back pain (daily pain for > 6 months) is one of the most prevalent and disabling complaints in VA healthcare. Effective treatment remains elusive. Most cases are not surgical candidates. Medical treatment relies upon non-steroidal anti-inflammatory drugs, opioids, and noradrenergic antidepressants. Among these the strongest evidence arguably supports use of noradrenergic antidepressants as analgesics, at lower concentrations than used to treat mood disorders, but only 50% of patients typically achieve satisfactory analgesia, and fewer show improved everyday function. A more integrated approach seems needed, particularly because evidence indicates that analgesia alone may not enhance everyday function. Research across a broad spectrum of psychiatric and medical disorders suggests that combining pharmacotherapy with cognitive behavioral therapy (CBT) improves outcomes. Leading authorities in chronic pain have called for studies that test multi-component versus single-modality therapies. Chronic back pain would seem to be the ideal target for a combination of an antidepressant and CBT, but no research addresses the efficacy of this integrated model for this population. We propose to test the utility of a "personalized medicine" approach (targeted low concentration antidepressant treatment with desipramine) plus brief CBT to provide analgesia, and improved function and life quality in chronic back pain. If successful this targeted intervention could be easily packaged and exported to primary care providers. The design is a 4-arm, 8-week, parallel groups, randomized clinical trial in men and women with chronic low back pain (N=200 total, 50 per arm) comparing 1) Antidepressant pharmacotherapy (desipramine, concentration15-65 ng/mL) + CBT; 2) Antidepressant pharmacotherapy alone; 3) CBT + Placebo Medication; and 4) Placebo Medication. One-month follow-up will test durability of effects. We propose a pragmatic clinical trial to test the utility of combined treatment rather than an explanatory clinical trial to establish therapeutic mechanisms. Therefore we will use placebo medication but not control for the non-specific effects of CBT (ie, therapist contact time) in this stage of research. Included will be men and women, aged 18-70, attending primary care clinics with chronic low back pain of at least "moderate" intensity (pain > 4 on 0-10 numeric pain rating scale) attributed to degenerative disc or joint disease. Excluded will be individuals with current major depression, substance use disorders, or co-morbid serious medical illness which could confound interpretation of outcomes. The primary analytic strategy will be intent-to-treat. We hypothesize that combination antidepressant + CBT will be superior to all other conditions. The primary efficacy assessment will be mean pain intensity (Descriptor Differential Scale) at exit. Secondary outcomes will be function (Roland and Morris Disability Questionnaire) and life quality (Short Form-36). Reassessment one month post-treatment will evaluate persistence of efficacy. Exploratory analyses will assess potential mediating and moderating variables of outcomes. PUBLIC HEALTH RELEVANCE: Project Narrative: Relevance to Veterans Health Back pain, a major and treatment-resistant medical problem for the VA, affects a substantial proportion of veterans, resulting in adverse effects on daily functioning comparable to that associated with coronary artery disease, hypertension, diabetes, and chronic obstructive lung disease (Wipf 1997). In the past decade the prevalence of chronic, impairing back pain tripled in the general population, where it exceeds 10% (Freburger et al 2009). Recent cohorts (Gulf War, OEF/OIF) of veterans report even higher rates, where chronic back pain exceeds 30% (Kang et al 2000, Cohen et al 2005). Rigorously controlled clinical trials of the type we propose could contribute to safer, more cost-efficient, and more effective back pain treatment.

描述（由申请人提供）： 项目摘要慢性背痛（每天疼痛> 6个月）是VA Healthcare中最普遍，最禁用的投诉之一。有效的治疗仍然难以捉摸。大多数病例不是手术候选人。医疗依赖于非甾体类抗炎药，阿片类药物和去甲肾上腺素能的抗抑郁药。在这些证据中，可以说，最有力的证据支持使用去甲肾上腺素能作为镇痛药，浓度低于治疗情绪障碍的浓度，但只有50％的患者通常可以达到令人满意的镇痛，并且更少的表现出改善的日常功能。似乎需要采用更整合的方法，尤其是因为证据表明仅镇痛可能不会增强日常功能。多种精神病和医学疾病的研究表明，将药物治疗与认知行为疗法（CBT）相结合可改善结果。慢性疼痛的主要当局要求进行研究，以测试多组分与单模式疗法。慢性背痛似乎是组合抗抑郁药和CBT的理想目标，但没有研究涉及该综合模型对该人群的功效。我们建议测试“个性化医学”方法的实用性（靶向低浓度的抗抑郁药对载蛋白）以及简短的CBT来提供镇痛，并改善了慢性背痛的功能和生活质量。如果成功，这种目标干预措施很容易包装并出口到初级保健提供者。该设计是一个4臂，8周平行的组，在慢性腰痛的男性和女性中随机临床试验（n = 200，每只手臂50），比较1）抗抑郁药药物疗法（desipramine，浓度15-65 ng/ml） + CBT; 2）仅抗抑郁药疗法； 3）CBT +安慰剂药物； 4）安慰剂药物。一个月的随访将测试效果的持久性。我们提出了一项务实的临床试验，以测试合并治疗的实用性，而不是建立治疗机制的解释性临床试验。因此，在研究阶段，我们将使用安慰剂药物，但不能控制CBT（即治疗师接触时间）的非特异性作用。其中包括18-70岁的男性和女性，参加了慢性下背部疼痛至少“中度”强度的初级保健诊所（疼痛> 4在0-10数字疼痛评分量表上）归因于退行性椎间盘或关节疾病。排除的将是患有当前重度抑郁症，药物使用障碍或合并严重的医学疾病的人，这可能会混淆结果的解释。主要的分析策略将是意图对待的。我们假设组合抗抑郁药 + CBT将优于所有其他条件。主要功效评估将是出口处的平均疼痛强度（描述尺度尺度）。次要结果将是功能（Roland and Morris残疾问卷）和生活质量（简短的表格-36）。治疗后一个月的重新评估将评估功效的持久性。探索性分析将评估潜在的介导和调节结果变量。 公共卫生相关性： 项目叙述：与退伍军人健康背痛有关，这是VA的主要且耐药的医疗问题，会影响退伍军人的很大一部分，从而对每日功能产生不利影响，与冠状动脉疾病，高血压，糖尿病和慢性阻塞性肺部疾病相比，这与日常功能相比（WIPF 1997）。在过去的十年中，慢性，背痛的患病率在一般人群中超过10％（Freburger等，2009年）。退伍军人最近的队列（墨西哥湾战争，OEF/OIF）报告了更高的率，在慢性背痛超过30％（Kang等，2000，Cohen等，2005）。我们提出的类型的严格控制临床试验可能会导致更安全，更具成本效益和更有效的背痛治疗。