Amantadine for multiple sclerosis-related fatigue: a systematic review and meta-analysis of randomized controlled trials.
Murilo Marmori Cruccioli, Pedro Henrique Teixeira Carneiro, Jorge Ferreira Jasmineiro Pitanga et al.
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In 30 seconds
This systematic review and meta-analysis assessed amantadine versus placebo for fatigue in people with multiple sclerosis, pooling nine randomized controlled trials involving 601 patients. Amantadine was not associated with a significant reduction in fatigue severity (SMD -0.22; [95% CI -0.72; 0.27]; p = 0.37). It was associated with higher odds of insomnia (OR = 2.33; [95% CI 1.27; 4.29]; p = 0.006). The authors conclude that the evidence does not support amantadine’s effectiveness for MS-related fatigue and raises concern about adverse effects, particularly insomnia.
Key findings
- Across nine RCTs involving 601 patients, fatigue severity did not differ significantly between amantadine and placebo (SMD -0.22; [95% CI -0.72; 0.27]; p = 0.37).
- Amantadine was associated with higher odds of insomnia than placebo (OR = 2.33; [95% CI 1.27; 4.29]; p = 0.006).
Why it matters
Fatigue is common in multiple sclerosis and can impair daily functioning, so treatments need evidence of benefit as well as acceptable tolerability. This pooled analysis found no significant fatigue reduction with amantadine while identifying increased odds of insomnia. The findings help clarify the balance of evidence for a commonly prescribed pharmacologic option.