Hartman et al. (2026)
- Authors: Noam Hartman, Dominik Ivkic, Marie Celine Dorczok, Ina Bozic, Lutz Reinfried, Anna-Christina Moser, Gernot Fugger, Birgit Ludwig, Florian Buchmayer, Marie Spies, Ana Weidenauer, Lucie Bartova
- Institutes: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Publisher: Psychopraxis. Neuropraxis (Springer)
- Link: DOI
Summary
This review establishes a neurobiological framework for using existing psychiatric medications to treat the debilitating cognitive and emotional symptoms of Long COVID and ME/CFS. By identifying shared pathways such as neuroinflammation and neurotransmitter imbalances, it provides a scientific basis for clinicians to explore off-label treatments while awaiting definitive clinical trial results. The paper highlights that many readily available drugs may offer significant relief for the ‘brain fog’ and fatigue that currently lack standard curative treatments.
What was researched?
The study investigated the neurobiological rationale and clinical potential of drug repurposing for Long COVID (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It focused on how existing psychotropic medications might address common symptoms like neuroinflammation, cognitive impairment, and neurotransmitter imbalances.
Why was it researched?
Researchers sought to address the urgent need for therapeutic options for LC and ME/CFS, noting significant symptom overlap with psychiatric disorders. The work is motivated by evidence of shared biological mechanisms, including altered neuroplasticity and cerebrovascular dysfunction in post-viral states.
How was it researched?
The authors conducted a comprehensive review of neurobiological findings and existing clinical case reports regarding off-label drug use. They analyzed the mechanisms of action for various substances to determine their suitability for targeting the specific neuropsychiatric symptoms observed in post-viral syndromes.
What has been found?
The review identified several promising candidates for repurposing, including phytotherapeutics like Silexan 💊 and Ginkgo biloba 💊 (EGb 761). It also highlighted antidepressants such as SSRIs 💊, SNRIs 💊, Bupropion 💊, Vortioxetine 💊, Mirtazapine 💊, and Tianeptine 💊. Additionally, augmentation strategies using Aripiprazole 💊, Daridorexant 💊, or (Es)Ketamine 💊 were found to have plausible benefits based on early clinical observations.
Discussion
The paper notes that while the neurobiological rationale is strong, current evidence often relies on case reports and small-scale observations. There is a critical need for large-scale, randomized controlled trials to validate these off-label approaches and ensure their efficacy specifically for the LC and ME/CFS populations.
Conclusion & Future Work
Psychopharmacological repurposing is a feasible and theoretically sound approach to managing neuropsychiatric symptoms in post-viral syndromes. The authors conclude that systematic clinical testing of these substances is the necessary next step to establish standardized treatment protocols.