Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose-Response Relationships

Objective: This study explores dose-response relationships when treating fibromyalgia with low-dose naltrexone.

Design: A single-blinded clinical trial was carried out using the "up-and-down" method.

Subjects: 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.

Methods: 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.

Results: A total of 27 subjects were included in the study; two subjects were withdrawn.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.

Conclusions: 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.