2026 American Academy of Neurology Abstract Website

Objective:

we designed this systematic review and network meta-analysis to compare the efficacy of Amantadine, Adderall, modafinil, and methylphenidate in treating MS-related fatigue, and improving processing speed in patients with MS.

Background:

Fatigue is a disabling symptom of multiple sclerosis (MS) with an unknown etiology. Various medications are used to treat MS-related fatigue, but none of the available studies directly compared the head-to-head efficacy of all these medications. Also, impaired processing speed is among first complaints in these patients.

Design/Methods:

PubMed, Scopus, EMBASE, PsycINFO, Web of Science, and Google Scholar were thoroughly searched by two independent researchers on March 1^st, 2025.

Mean difference (SMD) was used as the effect size, and surface under the cumulative ranking curve (SUCRA) was applied to rank interventions.

Results:

The literature search identified 1,878 records, of which 74 full-text articles were evaluated in detail, and 16 studies were ultimately included in the systematic review.

For fatigue severity, none of the medications were superior to placebo. For fatigue impact, only amantadine was superior to placebo. For processing speed, none of the medications outperformed placebo, and methylphenidate was associated with a significant negative effect on the SDMT (Symbol Digit Modalities Test) score.

Conclusions:

Among the prescribed medications for managing MS-related fatigue, only amantadine was found to be superior to placebo in improving the impact of fatigue on patients’ lives.