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（每天疼痛超过 6 个月）是 VA 医疗保健中最普遍和最致残的投诉之一。有效的治疗仍然难以实现。大多数病例不适合手术。药物治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。其中最有力的证据可以说支持使用去甲肾上腺素能抗抑郁药作为镇痛药，其浓度低于治疗情绪障碍的浓度，但通常只有 50% 的患者能够达到满意的镇痛效果，而表现出日常功能改善的患者则更少。似乎需要一种更综合的方法，特别是因为有证据表明单独镇痛可能无法增强日常功能。对广泛的精神和医学疾病的研究表明，将药物疗法与认知行为疗法 (CBT) 相结合可以改善治疗结果。慢性疼痛领域的权威人士呼吁开展研究来测试多成分疗法与单一疗法的对比。慢性背痛似乎是抗抑郁药和 CBT 联合治疗的理想目标，但没有研究探讨这种综合模型对该人群的功效。我们建议测试“个性化医疗”方法（使用地昔帕明进行针对性低浓度抗抑郁治疗）加短暂 CBT 的效用，以提供镇痛、改善慢性背痛的功能和生活质量。如果成功，这种有针对性的干预措施可以很容易地打包并输出给初级保健提供者。该设计是一项 4 组、8 周、平行组、随机临床试验，受试者为患有慢性腰痛的男性和女性（总共 N = 200 人，每组 50 人），比较 1) 抗抑郁药物治疗（地昔帕明，浓度 15-65 ng/毫升）+ CBT； 2）单纯抗抑郁药物治疗； 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。我们建议进行一项实用的临床试验来测试联合治疗的效用，而不是进行一项解释性临床试验来建立治疗机制。因此，在这一阶段的研究中，我们将使用安慰剂药物，但不控制 CBT 的非特异性效应（即治疗师接触时间）。其中包括年龄 18-70 岁、因退行性椎间盘或关节疾病而患有至少“中度”强度（0-10 数字疼痛评级量表中疼痛 > 4）的慢性腰痛的男性和女性。目前患有重度抑郁症、药物滥用障碍或合并严重疾病的个体将被排除在外，这些疾病可能会混淆结果的解释。主要分析策略将是意向治疗。我们假设抗抑郁药 + CBT 组合将优于所有其他条件。主要疗效评估将是退出时的平均疼痛强度（描述符差异量表）。次要结果是功能（罗兰和莫里斯残疾问卷）和生活质量（简表 36）。治疗后一个月重新评估将评估疗效的持续性。探索性分析将评估结果的潜在中介和调节变量。 公共卫生相关性： 项目叙述：与退伍军人健康的相关性 背痛是退伍军人管理局的一个主要且难以治疗的医疗问题，影响着相当大比例的退伍军人，对日常功能造成的不利影响与冠状动脉疾病、高血压、糖尿病和糖尿病相关的影响相当。慢性阻塞性肺病（Wipf 1997）。在过去十年中，普通人群中慢性损害性背痛的患病率增加了两倍，超过 10%（Freburger 等，2009）。最近的退伍军人队列（海湾战争、OEF/OIF）报告了更高的比率，其中慢性背痛超过 30%（Kang 等人 2000 年，Cohen 等人 2005 年）。我们建议的这种类型的严格对照临床试验可以有助于更安全、更具成本效益和更有效的背痛治疗。