Review Efficacy of pharmacologic treatments for fatigue in multiple sclerosis: A systematic review and meta-analysis, 2025, Toljana et al

Efficacy of pharmacologic treatments for fatigue in multiple sclerosis: A systematic review and meta-analysis

Karlo Toljana, Albert Aboseifb, Moein Amina

Highlights
• Amantadine and modafinil are the most studied medications for fatigue in MS.
• In a pooled analysis, medications demonstrated minimal to no efficacy for improving fatigue severity in MS.
• The clinical significance of the medication effect is uncertain.
• Side effects associated with these medications may limit tolerance.

Background
Fatigue is commonly experienced amongst persons with multiple sclerosis (PwMS), decreasing quality of life and increasing the economic burden of care. Several pharmacologic treatments have been studied in randomized clinical trials (RCTs) for fatigue in MS, with conflicting results.

Methods
We performed a systematic search for RCTs through PubMed and CENTRAL to determine the efficacy and tolerability of amantadine, modafinil, methylphenidate, and 4-aminopyridine as treatments for fatigue in adults with MS in comparison to placebo or other interventions. Outcomes were fatigue severity as measured by Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), or Visual Analog Scale, and frequency of discontinuation due to side effects. Forest plots were generated (random effects model), standardized mean differences (SMD) were used for continuous outcomes, and risk ratio was calculated for the dichotomous outcome. The risk of bias was assessed with the Cochrane risk-of-bias tool, and GRADEpro GDT was used to summarize the evidence.

Results
Of 259 screened studies, 16 met the inclusion criteria for this review. SMD showed a change of -0.26 (95 % CI, -0.54, 0.01) in the direction of medications, representing a decrease of 0.29 in FSS or 3.90 in MFIS (minimally important difference is 0.45 for FSS and 4 for MFIS). The pooled risk ratio for discontinuation was 2.11 (95 % CI, 1.19, 3.77), favoring controls. Most studies were without substantial risk of bias, but the certainty of evidence was low.

Conclusion
The studied medications have minimal to no efficacy and an uncertain clinical significance in reducing fatigue in PwMS.

Link | PDF (Multiple Sclerosis and Related Disorders) [Open Access]

 

I have family with MS, I’m not surprised by these results. The family member is the only one that understands my fatigue.