Synthesize current data about using low dose Naltrexone in symptom management for ME/CFS and long COVID.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Covid fatigue are two debilitating disorders causing symptoms like persistent fatigue, cognitive impairment, and pain through unknown mechanisms involving neuroinflammatory mechanisms. As relatively new pathologies, they lack research and appropriate treatment regimen needed for patient improvement. Naltrexone, an opioid receptor antagonist (usually used for opioid and alcohol dependence), has proposed in low doses an immunomodulatory effect suppressing microglial activation and reducing inflammatory cytokines which can decrease the symptom severity experienced by many patients.

We conducted a systematic literature review following PRISMA protocols. PubMed database was searched with keywords "naltrexone," “long Covid” and "ME/CFS". Resulting in 26 studies. We evaluated age, sex, dose, symptom progression, and side effects.

We included 9 studies reporting 1,449 patients with a mean age of 46.4 years. From those 36 (2.4%) diagnosed with ME/CFS and 1,413 (97.5%) long covid patients. The distribution is as follows 75.8% were female, and 24.2% male. Treatment dose varied from 3-4 mg/day (44%), 4-5 mg/day (44%), and 5-6 mg/day (12%) over an average period of 7 months. Improvement was shown after the allotted times showing decreased fatigue (66%), brain fog (44%), dysautonomia (11%), shortness of breath (11%), sleep (33%), pain (56%), and mood (22%). Dosage didn’t present a significant change in the symptom management. 100% of the studies reported minimal patients presenting diarrhea and fatigue. Of the 9 studies, 1 study involving ten patients didn’t provide any change to symptom severity.

Naltrexone in low doses can help improve the quality of life of patients living with ME/CFS and Post Covid Fatigue syndrome reducing the major symptoms like brain fog, fatigue, sleep disturbances, and mood. Due to increase incidence post-COVID, further research is imperative for innovative and personalized patient management.