What is the relationship between Amantadine (an antiviral and antiparkinsonian medication) and post-COVID-19 fatigue?

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Last updated: May 12, 2025View editorial policy

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From the Guidelines

Amantadine may be considered as a treatment option for post-COVID fatigue, though it is not FDA-approved specifically for this purpose, and its use should be based on individual patient assessment and part of a comprehensive approach. The treatment of post-COVID fatigue is complex and multifaceted, involving various mechanisms and symptoms, as outlined in recent studies 1.

Key Considerations

  • Typical dosing of amantadine starts at 100mg once daily, potentially increasing to 100mg twice daily after 1-2 weeks if tolerated, with treatment duration varying but often continuing for 2-3 months with periodic reassessment.
  • Amantadine works by enhancing dopamine release and blocking NMDA receptors, which may help improve energy levels and reduce fatigue symptoms.
  • Patients should be aware of potential side effects including insomnia, dizziness, and hallucinations, and the medication should be taken earlier in the day to minimize sleep disturbances.
  • Those with kidney disease, seizure disorders, or heart conditions should use caution and discuss with their healthcare provider before starting.

Comprehensive Approach

  • The use of amantadine should be part of a comprehensive approach that includes gradual physical activity, good sleep hygiene, and proper nutrition, as suggested by recent findings 1.
  • Other treatment options, such as pacing, cognitive pacing, and low-dose naltrexone, may also be considered, as outlined in Table 1 of the study 1.
  • It is essential to note that the current treatment options are based on small-scale pilot studies in long COVID or what has been effective in other diseases, and several additional trials are in progress 1.

Prioritization of Treatment

  • The prioritization of treatment options should be based on individual patient assessment, taking into account the specific constellation of symptoms and biological mechanisms involved, as suggested by the study 1.
  • A comprehensive approach that addresses the complex and multifaceted nature of post-COVID fatigue is crucial for improving patient outcomes and reducing morbidity, mortality, and improving quality of life.

From the Research

Post-COVID-19 Fatigue and Amanatadine

  • Post-COVID-19 fatigue is a common and debilitating symptom experienced by many COVID-19 survivors, with a significant proportion of individuals reporting fatigue 12 or more weeks after COVID-19 diagnosis 2.
  • A systematic review of post-COVID-19 fatigue identified potential risk factors, including old age, female sex, severe clinical status in the acute phase of infection, and a high number of comorbidities 3.
  • Several treatment approaches have been tested for post-COVID-19 fatigue, including a Chinese herbal formulation, molecular hydrogen inhalation, hyperbaric oxygen therapy, and enhanced external counterpulsation 3.
  • A randomized open-label clinical trial found that Amantadine significantly reduced fatigue levels in patients with post-COVID-19 fatigue, suggesting its potential as an effective treatment for this condition 4.

Mechanism and Efficacy of Amanatadine

  • The exact mechanism of Amantadine in reducing post-COVID-19 fatigue is not fully understood, but it may be related to its antiviral and anti-inflammatory properties 4.
  • The study found that Amantadine significantly improved fatigue levels, as measured by the Visual Analog Fatigue Scale and Fatigue Severity Scale questionnaires, compared to the control group 4.
  • The results of this study suggest that Amantadine may be a useful treatment option for post-COVID-19 fatigue, but further research is needed to confirm its efficacy and safety in larger populations 4.

Comparison with Other Treatments

  • Other treatments, such as antidepressants, have also been studied for their potential to reduce post-COVID-19 fatigue and other symptoms 5.
  • A scoping review found that antidepressants, particularly fluvoxamine, may have a preventive effect against progression to severe COVID-19 and against the development of Long COVID, including fatigue 5.
  • However, the evidence for the use of antidepressants in post-COVID-19 fatigue is still limited, and further research is needed to fully understand their potential benefits and risks 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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