Efficacy and safety of low-dose naltrexone for the management of fibromyalgia: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

Background: Fibromyalgia is characterized by the presence of chronic widespread pain that may impair patient's quality of life. Currently, the use of naltrexone as a therapeutic agent for fibromyalgia is not supported by enough evidence, especially from randomized controlled trials (RCTs). This study aims to analyze the efficacy and safety of low-dose naltrexone (LDN) for the management of fibromyalgia.

Methods: A comprehensive search was conducted on the Scopus, Medline, ClinicalTrials.gov, and Cochrane Library databases up until May 20th, 2024. This review incorporates RCTs that examine the comparison between LDN and placebo in fibromyalgia patients. We employed random-effect models to analyze the odds ratio and mean difference (MD) for presentation of the outcomes.

Results: A total of 4 RCTs with 222 fibromyalgia patients were incorporated. The results of our meta-analysis showed a significant reduction in pain scores (MD: -0.86, 95% confidence interval [CI]: -1.20, -0.51, < 0.001, = 33%) and higher increment in pressure pain threshold (MD: 0.17, 95% CI: 0.08, 0.25, < 0.001, = 0%) among fibromyalgia patients who received LDN than those who only received a placebo. The fibromyalgia impact questionnaire revised and pain catastrophizing scale did not differ significantly between the two groups. LDN was also associated with higher incidence of vivid dreams and nausea, but showed no significant difference with the placebo in terms of serious adverse events, headache, diarrhea, and dizziness.

Conclusions: This study suggests the efficacy of LDN in mitigating pain symptoms for fibromyalgia patients with a relatively good safety profile.