Efficacy of Antidepressants in Chronic Back Pain

抗抑郁药治疗慢性背痛的疗效

• 批准号: 8195996
• 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 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8195996
• 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; Pain intensity; 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

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.

项目摘要 慢性背痛（每日疼痛> 6个月）是VA中最常见和致残的主诉之一 健康护理有效的治疗仍然是难以捉摸的。大多数病例不适合手术。医疗 依赖于非甾体抗炎药、阿片类药物和去甲肾上腺素能抗抑郁药。其中 最强有力的证据支持使用去甲肾上腺素能抗抑郁药作为镇痛药， 浓度比用于治疗情绪障碍，但只有50%的患者通常达到令人满意的 镇痛，更少的人表现出改善的日常功能。似乎需要采取一种更加综合的办法， 特别是因为有证据表明，单独的镇痛可能不会增强日常功能。研究 对广泛的精神和医学疾病的治疗表明，药物治疗与 认知行为疗法（CBT）可以改善结果。慢性疼痛领域的主要权威人士呼吁 测试多成分与单一模式治疗的研究。慢性背痛似乎是 这是抗抑郁药和CBT组合的理想目标，但没有研究涉及这种疗效 这一群体的综合模式。我们建议测试“个性化医疗”方法的效用 （用地昔帕明进行靶向低浓度抗抑郁药治疗）加上短暂的CBT以提供镇痛， 改善慢性背痛患者的功能和生活质量。如果成功的话，这种有针对性的干预措施可能会 易于包装和出口到初级保健提供者。 该设计是一项在男性和女性慢性低血糖患者中进行的4臂、8周、平行组、随机临床试验。 背痛（总共N=200，每组50）比较1）抗抑郁药物治疗（地昔帕明， 浓度15 -65 ng/mL）+ CBT; 2）单独的抗抑郁药物疗法; 3）CBT +安慰剂药物; 和4）安慰剂药物。一个月的随访将测试效果的持久性。我们提出了一个务实的临床 测试联合治疗效用的试验，而不是确定治疗效果的解释性临床试验 机制等因此，我们将使用安慰剂药物，但不控制CBT的非特异性作用（即， 治疗师接触时间）在这个阶段的研究。 包括18-70岁的男性和女性，患有慢性腰痛， 最低“中度”强度（0-10数字疼痛评定量表上疼痛> 4）归因于退行性椎间盘或关节 疾病排除的将是目前患有重度抑郁症、物质使用障碍或合并症的个人 可能混淆结果解释的严重疾病。主要的分析策略是 我们假设联合抗抑郁药+ CBT将优于所有其他条件的上级。 主要疗效评估将是退出时的平均疼痛强度（描述符分类量表）。二次 结果将是功能（罗兰和莫里斯残疾问卷）和生活质量（简表-36）。 治疗后1个月的重新评估将评价疗效的持续性。探索性分析将评估 结果的潜在中介变量和调节变量。