Bruun-Plesner Karin, Blichfeldt-Eckhardt Morten Rune, Vaegter Henrik Bjarke, Lauridsen Joergen T, Amris Kirstine, Toft Palle
Pain Research Group, Pain Centre, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Pain Med. 2020 Oct 1;21(10):2253-2261. doi: 10.1093/pm/pnaa001.
This study explores dose-response relationships when treating fibromyalgia with low-dose naltrexone.
A single-blinded clinical trial was carried out using the "up-and-down" method.
Subjects included women with a diagnosis of fibromyalgia aged 18-60 years who had been referred to treatment at a public pain clinic at a Danish university hospital.
The test doses were in the range 0.75-6 mg, and the dosing interval was 0.75 mg. The method was sequential and allowed predicting the dose effective in 50% (ED50) and 95% (ED95) of the subjects when the dose had shifted direction 10 times, and six pairs of "up-and-down" data were available.
A total of 27 subjects were included in the study; two subjects were withdrawn. After inclusion of 25 evaluable subjects, the dose estimates were calculated as 3.88 mg for ED50 and 5.40 mg for ED95. As a secondary outcome, the effects on 10 common fibromyalgia symptoms were evaluated. A high interindividual variation was observed both in the symptom presentation at baseline and in which symptoms were reduced by low-dose naltrexone.
This study is the first to explore dose-response relationships in the treatment of fibromyalgia with low-dose naltrexone. Future placebo-controlled randomized clinical trials are needed, and according to our findings, 4.5 mg, which has previously been used, seems to be a relevant test dose. We recommend that future studies include additional nonpain fibromyalgia symptoms as outcome measures.
本研究探讨低剂量纳曲酮治疗纤维肌痛时的剂量-反应关系。
采用“上下法”进行单盲临床试验。
受试者包括年龄在18 - 60岁、被诊断为纤维肌痛且已被转诊至丹麦大学医院公共疼痛诊所接受治疗的女性。
试验剂量范围为0.75 - 6毫克，给药间隔为0.75毫克。该方法是序贯性的，当剂量方向改变10次且有六对“上下”数据可用时，可预测50%（ED50）和95%（ED95）受试者的有效剂量。
共有27名受试者纳入研究；两名受试者退出。纳入25名可评估受试者后，计算出ED50的剂量估计值为3.88毫克，ED95为5.40毫克。作为次要结果，评估了对10种常见纤维肌痛症状的影响。在基线症状表现以及低剂量纳曲酮减轻哪些症状方面均观察到个体间的高度差异。
本研究首次探讨低剂量纳曲酮治疗纤维肌痛的剂量-反应关系。未来需要进行安慰剂对照的随机临床试验，根据我们的研究结果，先前使用的4.5毫克似乎是一个合适的试验剂量。我们建议未来的研究将额外的非疼痛性纤维肌痛症状纳入结局指标。
