Efficacy of Antidepressants in Chronic Back Pain

描述（由申请人提供）： 慢性背痛（每日疼痛> 6个月）是VA医疗保健中最普遍和致残的投诉之一。有效的治疗仍然是难以捉摸的。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，浓度低于用于治疗情绪障碍，但只有50%的患者通常达到满意的镇痛效果，更少的患者显示日常功能改善。似乎需要一种更综合的方法，特别是因为有证据表明，单独的镇痛可能不会提高日常功能。对广泛的精神和医学疾病的研究表明，药物治疗与认知行为治疗（CBT）相结合可以改善结果。慢性疼痛领域的主要权威人士呼吁进行多成分与单一模式疗法的研究。慢性背痛似乎是抗抑郁药和CBT组合的理想目标，但没有研究讨论这种综合模型对这一人群的疗效。我们建议测试“个性化药物”方法（用地昔帕明进行靶向低浓度抗抑郁药治疗）加简短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出口到初级保健提供者。该设计是在患有慢性下腰痛的男性和女性中进行的4臂、8周、平行组、随机临床试验（总共N=200，每组50），比较1）抗抑郁药物疗法（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试验，以测试联合治疗的效用，而不是一个解释性的临床试验，以建立治疗机制。因此，在本研究阶段，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）。入选者包括18-70岁的男性和女性，因退行性椎间盘或关节疾病导致的至少“中度”强度的慢性腰痛（0-10数字疼痛评分量表上疼痛> 4）就诊于初级保健诊所。排除当前患有严重抑郁症、物质使用障碍或可能混淆结局解释的合并严重医学疾病的个体。主要的分析策略将是意向治疗。我们假设抗抑郁药+ CBT联合治疗将上级所有其他条件。主要疗效评估将是退出时的平均疼痛强度（描述符分类量表）。次要结局为功能（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。 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和难治性的医学问题，影响了相当大比例的退伍军人，对日常功能的不良影响与冠状动脉疾病、高血压、糖尿病和慢性阻塞性肺病相关的不良影响相当（Wipf 1997）。在过去十年中，一般人群中慢性损害性背痛的患病率增加了两倍，超过10%（Freburger et al 2009）。最近的退伍军人队列（海湾战争，OEF/OIF）报告的发病率甚至更高，其中慢性背痛超过30%（Kang et al 2000，Cohen et al 2005）。我们建议的严格对照的临床试验类型可以有助于更安全，更经济，更有效的背痛治疗。

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.