In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. Secondary outcomes included global impression of change, NP symptoms, sleep quality, quality of life, pain interference in daily activities, and mood. A larger number of responders were found in the methadone (68%), compared to the placebo (33%) arm; risk difference 33.6%; 95% confidence interval 13.0%-54.3%; P = 0.003; number needed to treat = 3.0. Methadone reduced pain intensity ( P < 0.001), burning ( P = 0.023), pressing ( P = 0.005), and paroxysmal dimensions ( P = 0.006) of NP. Methadone also improved sleep ( P < 0.001) and increased the patient's global impression of improvement ( P = 0.002). Methadone did not significantly impact quality of life, pain interference, or mood. Treatment-emergent adverse events occurred in all methadone- and in 73% of placebo-treated patients ( P < 0.001). No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.

中文翻译：

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METHA-NeP：美沙酮治疗神经性疼痛的有效性和安全性：一项对照随机试验。


在这项随机、双盲、平行安慰剂对照临床试验中，我们评估了美沙酮作为慢性神经性疼痛 （NP） 患者的附加疗法的疗效。86 例患者被随机分配接受美沙酮或安慰剂治疗 8 周。主要结局是使用 100 毫米疼痛视觉模拟量表从基线达到至少 30% 疼痛缓解的参与者比例。次要结局包括对变化的总体印象、NP 症状、睡眠质量、生活质量、日常活动中的疼痛干扰和情绪。与安慰剂组 （68%） 相比，美沙酮组 （33%） 发现更多的反应者;风险差 33.6%;95% 置信区间 13.0%-54.3%;P = 0.003;需要治疗的人数 = 3.0。美沙酮降低了 NP 的疼痛强度 （P < 0.001）、灼热感 （P = 0.023）、压迫 （P = 0.005） 和阵发性尺寸 （P = 0.006）。美沙酮还改善了睡眠 （ P < 0.001） 并增加了患者对改善的总体印象 （ P = 0.002）。美沙酮对生活质量、疼痛干扰或情绪没有显著影响。所有美沙酮患者和 73% 的安慰剂治疗患者均发生治疗中出现的不良事件 （P < 0.001）。没有发生严重的不良事件或死亡。据报道，美沙酮组有 2 名参与者因不良事件而停药，安慰剂组没有。美沙酮作为一线和/或二线药物 NP 优化治疗的附加组件，可提供卓越的镇痛效果、改善睡眠并增强对变化的总体印象，而不会与引起安全问题的重大严重不良反应相关。