Low-Dose Naltrexone Shows Promising Results in Reducing Long COVID Symptoms, Study Finds

WASHINGTON—A recent retrospective study suggests that patients with long COVID experienced notable improvements in symptoms and overall functioning after being prescribed low-dose naltrexone off-label. The analysis, based on electronic health records from Stanford University, found that 230 adults reported significant symptom burden reductions and functional gains following treatment.

The average composite score for seven key symptoms dropped by 5.1 points annually (95% CI -7.69 to -2.52, P<0.001) from a baseline average of 20, after adjusting for confounding factors. The mean number of symptoms also declined by 2.4 annual units (P=0.001). Functional status scores, measured on a 1-5 scale, improved by 0.32 points annually (P=0.011), indicating enhanced daily capability among patients.

“These results are encouraging, but the observational design limits causal conclusions,” noted study lead Brandon Aflak, JD, CNA, during a presentation at the IDWeek annual meeting. “Randomized, placebo-controlled trials are essential to validate safety and efficacy and determine its role in treatment protocols.”

Currently, no FDA-approved therapies exist for long COVID, and prior clinical trials of anti-inflammatories and antihistamines have yielded mixed outcomes. In a Paxlovid (nirmatrelvir-ritonavir) trial, the drug showed no advantage over placebo over three months, with 33-70% of patients in both groups reporting improvements in exercise tolerance, cognition, and autonomic function.

Long COVID is broadly defined as a chronic condition persisting beyond three months post-SARS-CoV-2 infection, characterized by fluctuating or progressive symptoms affecting multiple organ systems. A 2022 survey estimated that 6.9% of U.S. adults had ever experienced long COVID, with 3.4% reporting current symptoms.

Naltrexone, normally prescribed at 50-100 mg daily for opioid or alcohol use disorders, is used off-label at lower doses (median 4 mg in this study) for autoimmune and pain conditions. Its proposed mechanism in long COVID involves anti-inflammatory and immunomodulatory effects, as noted by Aflak.

The study cohort included adults with lab-confirmed SARS-CoV-2 infection and symptoms lasting at least 90 days post-infection. Participants underwent at least two clinic visits: a baseline assessment pre-treatment and follow-up while on naltrexone. The median patient age was 45.4 years, with 67% female, 85.2% fully vaccinated, and 70.9% infected with Omicron. Median time from infection to treatment initiation was 606 days, with an initial symptom count of 12 and a baseline composite score of 20.

Initial assessments revealed 55.7% of patients experienced reduced daily activity, 24.3% struggled with routine tasks, and 8.3% were bedridden. Post-treatment improvements were observed across multiple symptoms:

• Fatigue: -0.90 (95% CI -1.36 to -0.44, P<0.001)
• Brain fog: -1.27 (95% CI -1.84 to -0.69, P<0.001)
• Unrefreshing sleep: -1.06 (95% CI -1.59 to -0.53, P<0.001)
• Difficulty sleeping: -1.01 (95% CI -1.63 to -0.39, P=0.001)
• Post-exertional malaise: -1.44 (95% CI -2.11 to -0.77, P<0.001)

No significant changes were observed in headache or lightheadedness. Researchers cautioned that the lack of a control group introduces potential confounding risks, such as natural symptom resolution or impacts from concurrent therapies. Further research, including controlled trials, is critical to establishing naltrexone’s role in managing long COVID.

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