Low Dose Naltrexone Prescribing Practices for Children and Adolescents with Long COVID

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ABSTRACT Background Pediatric long COVID is associated with substantial symptom burden, yet evidence-based pharmacologic treatments remain limited. Low-dose naltrexone (LDN) has been proposed as a potential symptomatic therapy, but data in pediatric populations is lacking. Methods We conducted a retrospective analysis of pediatric and young adult patients (≤25 years) with a clinical diagnosis of long COVID who were prescribed LDN between July 2020 and July 2025 at three multidisciplinary pediatric long COVID programs in the United States. Deidentified clinical data were extracted from medical records. Outcomes included symptom prevalence, dosing practices, treatment continuation or discontinuation, adverse effects, and available patient-reported quality-of-life measures (PedsQL™ and PROMIS®). Findings The study included 62 patients (mean age, 15.6 years [range, 8–23]; 53.2% male and 46.8% female). Fatigue was nearly universal (98.4%), followed by headaches (87.1%), brain fog (74.2%), dizziness/lightheadedness (67.7%), anxiety (66.1%), and post-exertional malaise (56.5%). LDN-treated patients demonstrated a higher prevalence of neurocognitive and autonomic symptoms, compared to general clinic cohorts. Most patients (71.0%) reported no adverse effects; the most common were vivid dreams (9.7%) and insomnia (9.7%). At follow-up, 66.1% of patients remained on LDN. Medication discontinuation was attributed to perceived lack of benefit (43.8%) or side effects (25.0%). Baseline quality-of-life measures at initiation showed marked impairment: PedsQL Physical Health ( M= 38.0, SD =20.9) and Multidimensional Fatigue ( M= 35.7, SD =15.8) scores were low. PROMIS scores indicated reduced physical functioning ( M =36.8, SD =8.7) and cognitive functioning ( M =40.8, SD =7.6), with elevated fatigue (M =68.0, SD =10.4) and pain interference (M =58.6, SD =8.2) relative to population norms. The study was not designed to assess efficacy. Interpretation LDN was primarily prescribed to patients with prominent fatigue, neurocognitive symptoms, and autonomic dysfunction, and was generally well tolerated. These findings provide descriptive evidence of real-world prescribing practices and support the need for clinical trials to systematically evaluate LDN’s efficacy in pediatric long COVID.