Combination Therapy with Opioid and Duloxetine for Chronic Pain Management

 描述(由申请人提供)：慢性疼痛是一种具有重大医学和社会经济影响的衰弱状况。患有慢性疼痛的患者通常需要包括药物在内的多种治疗方式。目前有几类药物用于慢性疼痛治疗，包括非类固醇抗炎药、对乙酰氨基酚、阿片类药物、抗抑郁药、抗癫痫药物如加巴喷丁，以及局部用药。联合药物治疗的概念已经被知道了几十年，它指的是联合使用不同类别的药物，以达到改善疼痛缓解的主要目标。虽然阿片类药物是治疗中到重度疼痛的强效镇痛剂，但它们的使用往往因副作用而复杂化，有时还会产生不良结果，如成瘾和矛盾的阿片类药物诱导的痛敏(OIH)，特别是用于慢性疼痛治疗时。尽管临床医生使用阿片类药物作为单一药物治疗慢性疼痛并不常见，但很少有临床试验充分评估1)添加抗抑郁药等非阿片类药物附件是否可以改善阿片类止痛，以及2)与单独药物治疗相比，联合药物治疗中阿片类药物的总体使用量将减少。这一独特的HHS资助机会(PAR-14-225：阿片类药物治疗慢性疼痛的辅助药物的临床评估)既及时又具有临床意义，有助于填补这一重要临床问题的知识空白。在这项应用中，我们建议进行一项双盲、随机和安慰剂对照的临床研究，以检查5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)度洛西汀是否可以增强阿片类药物的止痛作用，并减少阿片类药物的总体使用。我们将招募有慢性(≥3个月)颈部或背部神经根性疼痛症状的受试者参加一项为期10周的研究，这些受试者目前正在经历不满意的疼痛缓解[视觉模拟评分：≥5/10]，尽管接受了至少三个月的非阿片类药物治疗。主要研究结果将是1)VAS疼痛评分的变化和2)研究期间总体和抢救阿片类药物的使用。次要结果将包括1)副作用概况，2)辍学率，3)功能状态，4)阿片类药物依赖，5)OIH， 6)尿药筛查。在方法上，我们将使用临床(VAS；问卷)和实验(定量感觉测试)疼痛评估工具。此外，我们将制定一项计划，将研究结果数据提供给管理阿片类药物治疗的临床医生，如针灸医院和社区医院的初级保健医生和护士从业者。我们期望这项研究将产生关于在慢性疼痛治疗中添加阿片类药物辅助剂的有效性或缺乏的重要数据。积极的治疗方案将有助于提高临床阿片类药物治疗的整体效果，减少不必要的阿片类药物剂量上升。

 DESCRIPTION (provided by applicant): Chronic pain is a debilitating condition with significant medical and socioeconomic implications. Patients with chronic pain often require multi-modality treatment including medications. Several categories of medications are currently used in chronic pain management, including non-steroidal anti- inflammatory drugs, acetaminophen, opioids, antidepressants, antiepileptic drugs such as gabapentinoids, and topical agents. The concept of combination drug therapy has been known for several decades, which refers to the combined use of different categories of medications in order to achieve improved pain relief as a primary goal. While opioids are strong analgesics for the treatment of moderate to severe pain, their use is often complicated by side effects and sometimes adverse outcomes such as addiction and paradoxical opioid-induced hyperalgesia (OIH), particularly when used for chronic pain management. Although it is uncommon for clinicians to use opioids as a single drug treatment for chronic pain, few clinical trials have adequately assessed whether 1) opioid analgesia could be improved by adding a non-opioid adjunct such as antidepressant and 2) overall opioid use in a combination drug therapy would be decreased as compared to a respective single drug therapy. This unique HHS funding opportunity (PAR-14-225: Clinical Evaluation of Adjuncts to Opioid Therapies for the Treatment of Chronic Pain) is both timely and clinically relevant, which helps fill a knowledge gap on this important clinical issue. In this application, we propose to conduct a double-blind, randomized, and placebo-controlled clinical study in order to examine whether duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid analgesia and reduce overall opioid use. We will recruit subjects with chronic (≥ 3 months) neck or back radicular pain symptoms to participate in a 10-week study, who are currently experiencing unsatisfactory pain relief [visual analog score (VAS): ≥ 5/10] despite on non-opioid treatment for at least three months. Primary study outcomes will be 1) changes in VAS pain score and 2) overall and rescue opioid use during the study. Secondary outcomes will include 1) side effect profile, 2) dropout rate, 3) functional status, 4) opioid dependece, 5) OIH, and 6) urine drug screening. Methodologically, we will use both clinical (VAS; questionnaries) and experimental (quantitative sensory testing) pain assessment tools. In addition, we will develop a plan to make the study outcome data available to clinicians who manage opioid therapies such as primary care physicians and nurse practitioners in both acedemic and community hospitals. We expect that this study will yield important data on the effectiveness, or lack thereof, of adding an adjunct to opioid therapy in chronic pain management. Positive outomes will help improve the overall effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.