Efficacy of Antidepressants in Chronic Back Pain

描述(由申请人提供)： 项目摘要慢性背痛(持续6个月的每日疼痛)是退伍军人医疗保健中最普遍和最令人丧失能力的主诉之一。有效的治疗方法仍然难以捉摸。大多数病例不适合做外科手术。医学治疗依赖于非类固醇抗炎药、阿片类药物和去甲肾上腺素能抗抑郁药。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抗抑郁剂作为镇痛剂，浓度低于用于治疗情绪障碍的药物，但只有50%的患者通常能达到令人满意的镇痛效果，而且很少有患者表现出日常功能的改善。似乎需要一种更综合的方法，特别是因为有证据表明，单靠止痛可能不会增强日常功能。对广泛的精神和医学障碍的研究表明，将药物治疗与认知行为治疗(CBT)相结合可以改善结果。慢性疼痛方面的主要权威人士呼吁进行研究，测试多组分与单一模式的治疗方法。慢性背痛似乎是抗抑郁药物和CBT联合使用的理想靶点，但没有研究表明这种综合模型对这一人群的有效性。我们建议测试一种“个体化药物”方法(使用地塞帕明进行靶向低浓度抗抑郁药物治疗)加简单的CBT的有效性，以提供镇痛，并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到初级保健提供者。这项设计是一项为期4周、平行分组的随机临床试验，对患有慢性下腰痛的男性和女性(N=200人，每只手50人)进行比较：1)抗抑郁药物治疗(地昔帕明，浓度15-65 ng/mL)+CBT；2)单独抗抑郁药物治疗；3)CBT+安慰剂药物；以及4)安慰剂药物。一个月的随访将测试效果的耐久性。我们建议进行务实的临床试验来测试联合治疗的有效性，而不是通过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，但不会对CBT的非特异性影响(即治疗师接触时间)进行对照。将包括年龄18-70岁的男性和女性，他们到初级保健诊所就诊，慢性下腰痛的强度至少为“中等”(0-10数字疼痛分级标准中的疼痛&GT；4)，可归因于退行性椎间盘或关节疾病。排除的将是目前患有严重抑郁症、药物使用障碍或可能混淆对结果的解释的严重内科疾病的个人。主要的分析策略将是意向治疗。我们假设联合使用抗抑郁剂+CBT将优于所有其他条件。主要的疗效评估将是退出时的平均疼痛强度(描述性差异评分)。次要结果将是功能(罗兰和莫里斯残疾问卷)和生活质量(简表-36)。治疗后1个月复评将评估疗效的持续性。探索性分析将评估潜在的调节和调节结果的变量。 公共卫生相关性： 项目简介：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，对日常功能的不良影响可与冠状动脉疾病、高血压、糖尿病和慢性阻塞性肺疾病相媲美(WIPF 1997)。在过去的十年中，慢性、损伤性背痛在普通人群中的患病率增加了两倍，超过10%(Freburger等人，2009年)。最近的退伍军人队列(海湾战争，OEF/OIF)报告了更高的发病率，其中慢性背部疼痛超过30%(Kang等人，2000年，Cohen等人，2005年)。我们建议的这类严格受控的临床试验可能有助于更安全、更具成本效益和更有效的背痛治疗。

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.