TL;DR
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A retrospective review of 230 adults treated at Stanford’s Long COVID Clinic found lower reported symptom scores and improved functional status during low-dose naltrexone treatment. The study had no control group, so it cannot establish that the drug caused the changes; randomized, placebo-controlled trials are needed.
A retrospective study of 230 adults with long COVID found that patients reported fewer symptoms and better functioning after receiving prescriptions for low-dose naltrexone, researchers reported at the IDWeek meeting on October 26. Because the review had no control group, it cannot show that the drug caused the improvements or establish its effectiveness for long COVID.
The investigators analyzed electronic health records from Stanford’s Long COVID Clinic, covering patients seen between 2023 and December 2025. Participants were adults with laboratory-confirmed COVID-19 and symptoms lasting at least 90 days. To be included, each needed a clinic visit before starting naltrexone and at least one follow-up visit while taking it. The treatment was prescribed off-label.
After adjustment for other factors, the average seven-symptom composite score fell by an estimated 5.1 points per year from a baseline average of 20. The mean number of reported symptoms fell by an estimated 2.4 per year, while functional-stage scores improved by 0.32 points per year on a five-point scale. These are modeled annual changes from the study, not evidence that every patient improved by those amounts.
Reported gains included fatigue, brain fog, sleep problems and post-exertional malaise. The study did not find significant improvements in headache or lightheadedness. The median final dose was 4 mg. Patients’ median age was 45.4, 67% were women, and 85.2% were fully vaccinated; 70.9% had been infected with an Omicron variant. The median interval between infection and starting naltrexone was 606 days.
Why the Findings Matter
Long COVID can involve persistent, relapsing or progressive symptoms affecting one or more organ systems, and the burden in this cohort was substantial: 55.7% reported reduced daily activity, 24.3% struggled with normal daily activities, and 8.3% were described as incapacitated and bedridden. Reported changes in symptoms and functioning may help guide further research into possible treatments, but they do not establish a clinical benefit.
There are no FDA-approved therapies for long COVID, according to the report. The findings may interest patients and clinicians weighing options in an area with limited proven treatments. Yet without a comparison group, changes could reflect the condition’s natural course, other care, or factors the analysis did not capture. The results are a signal for controlled research, not a basis for concluding that naltrexone works.
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How Naltrexone Was Used
Naltrexone is FDA-approved to treat opioid use disorder and alcohol use disorder; in combination with bupropion, it is also used for obesity. The lower doses examined in this study are below the approved 50–100 mg doses described in the report and are used off-label in some settings, including for conditions such as fibromyalgia and pain management. The study did not test an FDA-approved long COVID indication.
Lead presenter Brandon Aflak, a Stanford fellow, said naltrexone may have anti-inflammatory and immunomodulatory effects that could be relevant to long COVID. That is a proposed rationale, not a mechanism demonstrated by this study. The report also notes that other treatment approaches have produced mixed results in trials; a cited study of nirmatrelvir-ritonavir did not find the active treatment outperformed placebo.
What the Clinic Review Cannot Show
The study was retrospective and uncontrolled: everyone included received a prescription, and there was no placebo or untreated comparison group. Long COVID symptoms can change over time, and the report says natural progression or concurrent treatments could have affected the observed results. Statistical adjustment cannot rule out those explanations or other sources of bias.
The findings also rely on patient records and self-reported symptoms and functioning. The report does not establish whether the improvements lasted after treatment, how patients who stopped or did not return to the clinic may differ, or whether the results apply to people treated in other settings. The study’s findings do not establish safety or efficacy, and the source does not provide a controlled comparison of side effects.
Controlled Trials Are Needed
The next research step identified by Aflak is a randomized, placebo-controlled trial to test whether low-dose naltrexone leads to better outcomes than placebo, assess safety, and clarify its possible place in long COVID care. The report does not give a timeline or say that such a trial has begun. Until stronger evidence is available, these clinic findings remain observational and do not establish a treatment recommendation.
Patients considering naltrexone should discuss its risks and appropriateness with a qualified clinician, particularly because it is an off-label use for long COVID. The study does not show that people should start, stop or change medication based on its results.
Key Questions
Did the study prove low-dose naltrexone treats long COVID?
No. It found an association between treatment and reported improvements, but its retrospective design and lack of a control group mean it cannot show that the drug caused them.
Which symptoms improved in the study?
Patients reported significant improvements in fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. Headache and lightheadedness did not improve significantly in the analysis.
What dose did participants take?
The median final dose was 4 mg. This was an off-label low-dose use; the study did not establish an appropriate dose for long COVID or recommend one.
What evidence is needed next?
The presenter said randomized, placebo-controlled trials are needed to assess whether the drug is effective and safe for long COVID and to determine its potential role in care.
Source: medpagetoday.com
