Modafinil reduces fatigue, improves quality of life in MS: Analysis
But use in trials linked to 30% increase in adverse events vs. placebo
Treatment with modafinil, a stimulant approved in the U.S. for treating certain sleep-related disorders, significantly reduced fatigue and improved overall quality of life when used in clinical trials for people with multiple sclerosis (MS), according to a review of published study data.
However, its use was linked to a 30% increase in adverse events such as insomnia and gastrointestinal symptoms when compared with a placebo.
According to the researchers, “future research comparing modafinil to other treatment modalities as well as pooling of more precise studies with similar intervention characteristics would be required to better inform clinical management.”
The study, “The use of modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta-analysis of controlled clinical trials,” was published in Brain and Behavior.
The researchers noted their belief that this study “serves as the most comprehensive quantitative review of the safety and efficacy of modafinil for the treatment of fatigue in patients with MS to date.”
Modafinial for MS leads to ‘meaningful reduction’ in fatigue
Excessive fatigue and daytime sleepiness are common symptoms of MS that have a significant impact on quality of life. While there now are multiple therapies that slow MS disease progression, these symptoms are still not well addressed by existing medications.
Modafinil is a stimulant, sold under the brand name Provigil, that has shown effectiveness in managing daytime fatigue in people with sleep disorders. It’s also sometimes prescribed off-label to MS patients, although “literature synthesizing data on the treatment of fatigue in MS with modafinil has been largely limited,” the researchers noted.
To know more about the effects of this treatment on MS fatigue, researchers in Pakistan, Nepal, and the U.S. reviewed data from published clinical trials that had tested modafinil against a control treatment.
Seven studies, involving a total of 590 participants, were included in the analysis. About half of the participants had received modafinil as a potential treatment for fatigue in MS, while the other half received either a placebo or L-carnitine, which is sometimes used as a supplement to reduce fatigue in certain diseases.
The patients had a mean age of 42.5 and were mostly women (71%); nearly three-quarters (72%) had relapsing-remitting MS (72%). Most of those assigned to modafinil received a daily dose of 200 mg, although some participants were given more than 400 mg daily. The duration of treatment, and the evaluation period, ranged from two to eight weeks.
A meta-analysis, which combined data from the multiple studies to identify overall trends with a greater statistical confidence, showed that modafinil use led to a significant reduction in fatigue compared with a placebo.
Our findings, across seven studies, demonstrate that modafinil leads to a statistically meaningful reduction in fatigue when compared with placebo.
The treatment was significantly more effective in two fatigue scales, namely the Modified Fatigue Impact Scale (MFIS) and the Epworth Sleepiness Scale (ESS). However, no significant differences were observed when using the Fatigue Severity Scale (FSS).
L-carnitine, used as a control in two studies, was generally more efficient than modafinil in reducing fatigue in the MFIS score, although the difference was not statistically significant.
Modafinil also contributed to a significantly better physical quality of life for patients compared with a placebo, but no significant differences were found for mental-health-specific aspects. Still, when mental and physical health quality of life were examined together, there was a significant benefit.
Regarding adverse events, reported in four studies, treatment with modafinil was associated with a 30% higher risk of causing an adverse event — most commonly insomnia or gastrointestinal problems — than was a placebo.
“Our findings, across seven studies, demonstrate that modafinil leads to a statistically meaningful reduction in fatigue when compared with placebo, as measured by MFIS and ESS,” the researchers wrote, adding that “these findings coincide with previous meta-analyses.”
Overall, the team found that “the data indicate that modafinil confers a therapeutic benefit in treating fatigue in patients with MS and improves overall QoL; however, there is a heightened risk of precipitating adverse events such as insomnia and gastrointestinal symptoms.”
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