Amantadine, fampridine, and methylphenidate are associated with improvements in fatigue-related functional burden among patients with multiple sclerosis (MS), although no medication is superior to placebo for reducing fatigue severity, according to a study published in Neurodegenerative Disease Management.

Researchers conducted a systematic review and network meta-analysis to compare the efficacy of pharmacologic treatments for MS-related fatigue. Eligible studies included randomized clinical trials or crossover trials evaluating medications used to treat MS-related fatigue in adults with MS. Outcomes included the Fatigue Severity Scale (FSS), which measures fatigue severity, and the Modified Fatigue Impact Scale (MFIS), which assesses the effects of fatigue on physical, cognitive, and psychosocial functioning.

A total of 15 studies published between 1995 and 2024 were included in the systematic review. Of these, 4 were crossover studies, and the most frequent countries of origin were the United States and Iran. In total, 940 patients in intervention arms and 662 patients in control arms were evaluated. In 4 studies, control groups were not placebo and instead included aspirin, ondansetron, fampridine, and cognitive behavioral therapy (CBT).

 

[T]reatment decisions should be individualized and consider patient-specific factors, including disability level, comorbid depression, sleep disorders, and functional priorities.

For fatigue severity, none of the medications was superior to placebo. Based on P score rankings, N-acetylcysteine (P score, 0.94), modafinil (P score, 0.63), and aspirin (P score, 0.55) ranked above placebo for improving fatigue severity, although standardized mean differences did not reach statistical significance.

For fatigue-related daily functioning measured using the MFIS, amantadine (mean difference [MD], −12.11; 95% CI −14.28 to −9.94), fampridine (MD, −14.05; 95% CI −22.59 to −5.52), and methylphenidate (MD, −5.25; 95% CI −8.44 to −2.06) were associated with statistically significant improvements compared with placebo. However, CBT (MD, 1.40; 95% CI −1.99 to 4.80) and modafinil (MD, 0.60; 95% CI −1.26 to 2.46) did not differ significantly from placebo.

The authors noted that previously proposed minimally important differences for the MFIS suggest that the improvements observed with amantadine and fampridine may be clinically meaningful, whereas the magnitude of benefit associated with methylphenidate did not exceed the suggested threshold despite reaching statistical significance.

Study limitations include the limited number of trials per comparison, clinical heterogeneity,  methodological heterogeneity, and the overall low-to-moderate certainty of evidence.

“[T]reatment decisions should be individualized and consider patient-specific factors, including disability level, comorbid depression, sleep disorders, and functional priorities,” the authors concluded.

This article originally appeared on Neurology Advisor