E1 ReplicatedPreliminaryPEM not requiredRCTPeer-reviewedMachine draft
Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial.
Tomassini, Valentina, Pozzilli, Carlo, Onesti, Emanuela et al. · Journal of the neurological sciences · 2004 · DOI
Quick Summary
This study compared two drugs used to treat fatigue: acetyl L-carnitine (ALCAR) and amantadine. Thirty-six people with multiple sclerosis who experienced fatigue took each drug for 3 months in turn, with a break between treatments. ALCAR was found to work better than amantadine at reducing fatigue severity, and fewer people stopped taking it due to side effects.
Why It Matters
Although this study focuses on MS rather than ME/CFS, it is relevant because acetyl L-carnitine was previously shown to help fatigue in chronic fatigue syndrome patients. Understanding which fatigue-treatment options work better and with fewer side effects may inform approaches applicable to ME/CFS, where treatment options are currently limited.
Observed Findings
- ALCAR produced statistically significant improvement on the Fatigue Severity Scale compared to amantadine (p=0.039)
- Only 1 of 36 patients withdrew due to adverse effects on ALCAR, compared to 5 patients on amantadine
- No significant differences were observed between treatments on secondary measures (Fatigue Impact Scale, depression, social function)
- Both treatments were completed by most participants over the 6-month trial period with 3-month washout
Inferred Conclusions
- Acetyl L-carnitine is more effective than amantadine for treating fatigue severity in MS patients
- Acetyl L-carnitine has a superior safety and tolerability profile compared to amantadine
- Secondary outcomes (mood, social impact) may not be sensitive enough to capture treatment differences, or ALCAR's benefits may be fatigue-specific
Remaining Questions
- Does acetyl L-carnitine work for fatigue in ME/CFS patients, given prior evidence of efficacy in that population?
- What is the optimal dose and duration of ALCAR treatment for maximum benefit?
- What is the mechanism of action by which ALCAR reduces fatigue in neurological conditions?
What This Study Does Not Prove
This study does not establish whether ALCAR works for ME/CFS fatigue, as it enrolled only MS patients with different pathophysiology. The small sample size (36 participants, with 6 withdrawals) limits generalizability. It does not explain the biological mechanism by which ALCAR reduces fatigue or determine optimal dosing.
Tags
Symptom:Fatigue
Method Flag:Small Sample
Metadata
- DOI
- 10.1016/j.jns.2003.11.005
- PMID
- 14759641
- Review status
- Machine draft
- Evidence level
- Replicated human evidence from multiple independent studies
- Last updated
- 8 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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