A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue, 2024, Harandi

A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue


Abstract
Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited research has explored effective treatments for post-COVID-19 fatigue.

This randomized controlled clinical trial assessed the impact of Amantadine on patients with post-COVID-19 fatigue. The intervention group received Amantadine for two weeks, while the control group received no treatment. Fatigue levels were assessed using the Visual Analog Fatigue Scale (VAFS) and Fatigue Severity Scale (FSS) questionnaires before and after the trial. At the study's onset, VAFS mean scores were 7.90 ± 0.60 in the intervention group and 7.34 ± 0.58 in the control group (P-value = 0.087). After two weeks, intervention group scores dropped to 3.37 ± 0.44, significantly lower than the control group's 5.97 ± 0.29 (P-value < 0.001). Similarly, FSS mean scores at the trial's commencement were 53.10 ± 5.96 in the intervention group and 50.38 ± 4.88 in the control group (P-value = 0.053). At the trial's end, intervention group scores decreased to 28.40 ± 2.42, markedly lower than the control group's 42.59 ± 1.50 (P-value < 0.001).

In this study, we report the safety, tolerability, and substantial fatigue-relieving effects of Amantadine in post-COVID-19 fatigue. The intervention demonstrates a statistically significant reduction in fatigue levels, suggesting Amantadine's potential as an effective treatment for this persistent condition.

https://www.nature.com/articles/s41598-024-51904-z

 

There was this CFS trial in 1997. The dosage of l-carnitine was 1g 3 times per day.
https://pubmed.ncbi.nlm.nih.gov/9018019/

Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome
A V Plioplys 1, S Plioplys
Affiliations

• PMID: 9018019
  
• DOI: 10.1159/000119325

Abstract


Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. Previous investigations have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and amantadine for treating CFS have not been previously reported. We treated 30 CFS patients in a crossover design comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week washout period between medicines. L-Carnitine or amantadine was alternately assigned as fist medicine. Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment, the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks of treatment, there was no statistically significant difference in any of the clinical parameters that were followed. However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18 studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration. The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine is a safe and very well tolerated medicine which improves the clinical status of CFS patients. In this study we also analyzed clinical and laboratory correlates of CFS symptomatology and improvement parameters.

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Amantadine (Gocovri) is used in the treatment of Parkinson, albeit its mechanism of action is poorly understood, and is used as an antiviral in influenza caused by type A influenzavirus. It acts as a nicotinic antagonist, dopamine agonist, and noncompetitive NMDA antagonist.

The basis for this trial are trials supposedly showing a positive result for addressing fatigue in MS (these are the papers the authors refer to 1 and 2 with the Cochrane report from 2007 rating the evidence as poor).

The cohorts of this trial looks very good in terms of gender, age and BMI and these things are decently matched between the Amantadine group and the control group, however almost half of the cohort was hospitalised.

However, glancing through the paper I'm not able to tell for how long the patients had been sick, what symptoms they have and whether they have been medicially evaluated and whether they actually have Long-Covid. According to recruitment page it seems that these people do not have Long-Covid but had Covid 30 to 60 days ago and still have some fatigue resulting from that, i.e. what the authors call "post Covid 19 fatigue". No diagnosis of Long-Covid is required with the only diagnosis required being that of recent Covid infection.

The dosage in the trial was 200mg of Amantadine daily for 2 weeks, which is very similar to the dosage in the CFS trial which @Dolphin linked above, albeit with a far shorter duration (2 weeks vs 2 months).

Given the choice of cohorts I can only classify this trial as meaningless to provide any insights into Long-Covid and it's use for patients with post Covid 19 fatigue would be extremely debatable.

 

Even though Amantadine appears to ease some of the ME fatigue experienced by a patient I know, the GI repercussions were too intense to continue taking it.