Is Low Dose Naltrexone Effective in the Management of Post-COVID Fatigue and Pain?

Background and/or Objectives: While naltrexone is typically prescribed for opioid or alcohol use disorder at doses of 25–150 mg/day, emerging evidence suggests that low-dose naltrexone (LDN, 1–5 mg/day) may alleviate chronic pain and fatigue in long-COVID patients. This study evaluates the clinical impact of LDN in adults with long-COVID in an outpatient setting.

Design: Retrospective chart review of patients over age 18 diagnosed with long-COVID who received LDN from April 1, 2021, to July 1, 2024.

Setting : Urban Veterans Affairs Medical Center Pain Clinic

Participants : Six veterans diagnosed with long-COVID who received LDN for chronic pain and fatigue refractory to traditional non-opioid interventions (medications, occupational and physical therapy, modalities)

Interventions: Patients were initiated on low-dose naltrexone ranging from 0.5 to 4.5 mcg (average initial dose: 3.94 mcg), with titration based on clinical response.

Main Outcome Measures: Verbal Pain Rating Scale and Fatigue Severity Scale (FSS)

Results: Data collected included demographics, comorbidities, prior pain therapies, LDN duration, adverse effects, FSS and serial verbal pain ratings. Primary endpoints were pain scale changes, therapy duration, and adverse effects. Secondary endpoints included therapies used prior to LDN initiation. No adverse drug reactions were reported. Two of six patients experienced clinically significant improvements in brain fog and fatigue. There was a slight reduction in overall pain scores after treatment with LDN. This change, however, was not significant across 2–3-month intervals.

Conclusions: The study was limited due to the low sample size. Although responses to LDN for pain and symptom management were not statically significant, the absence of side effects and potential improvement in select long-COVID symptoms support further exploration of LDN as a treatment option. More comprehensive studies are necessary to determine its efficacy in reducing chronic pain and associated symptoms in this population.