BACKGROUND Fatigue is the most common symptom of MS and has no effective pharmacotherapy. OBJECTIVE To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue. METHODS In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models. RESULTS In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (-0.10 point; 95% confidence interval (CI): -0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (-5.2 points; 95% CI: -10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (-13.5 point; 95% CI: -25.0, -1.98; p = 0.04). CONCLUSIONS Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.

中文翻译：

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低剂量氯胺酮治疗多发性硬化症相关疲劳的随机活性安慰剂对照试验

背景疲劳是MS最常见的症状，目前尚无有效的药物治疗。目的 确定低剂量氯胺酮输注治疗 MS 相关疲劳的耐受性、安全性和有效性。方法 在这项双盲、随机、活性安慰剂对照试验中，18 名患有多发性硬化症 (MS) 并报告疲劳的受试者接受了单次静脉输注氯胺酮 (0.5 mg/kg) 或咪达唑仑 (0.05 mg/kg)。主要结果是输注后 7 天内每日疲劳严重程度 (DFS) 的变化。次要结果包括在输注后第 28 天测量的疲劳严重程度量表 (FSS) 和改良疲劳影响量表 (MFIS)。我们使用混合效应模型分析了所有结果的变化。结果 总共有 18 名参与者入组；67% 的参与者接受了氯胺酮。氯胺酮的副作用是短暂的。7 天后没有观察到 DFS 的变化（-0.10 点；95% 置信区间 (CI)：-0.32, 0.12；p = 0.40）。我们观察到第 1 周 FSS 评分降低的趋势（-5.2 分；95% CI：-10.4, 0.14；p = 0.06），第 28 天 MFIS 评分有临床和统计学显着降低（-13.5 分；95% CI ：-25.0，-1.98；p = 0.04）。结论 氯胺酮输注安全且耐受性良好。虽然观察到 7 天后 DFS 没有变化，但二次分析表明氯胺酮输注有助于降低 MS 患者的长期疲劳严重程度。06），并且在第 28 天 MFIS 评分在临床和统计学上显着降低（-13.5 分；95% CI：-25.0，-1.98；p = 0.04）。结论 氯胺酮输注安全且耐受性良好。虽然观察到 7 天后 DFS 没有变化，但二次分析表明氯胺酮输注有助于降低 MS 患者的长期疲劳严重程度。06），并且在第 28 天 MFIS 评分在临床和统计学上显着降低（-13.5 分；95% CI：-25.0，-1.98；p = 0.04）。结论 氯胺酮输注安全且耐受性良好。虽然观察到 7 天后 DFS 没有变化，但二次分析表明氯胺酮输注有助于降低 MS 患者的长期疲劳严重程度。