A new study compared benefits of an accepted behavioral strategy, modafinil, and a combination of both therapies for fatigue in people with multiple sclerosis. They found that cognitive behavioral therapy, modafinil, and combination therapy were each linked to reduced fatigue effect in people with MS.

No single treatment is broadly effective for MS-related fatigue. Although existing behavioral and pharmacological therapies may each improve fatigue for some individuals, their comparative effectiveness and that of their simultaneous combination have not been studied. Furthermore, trials of MS‐fatigue interventions have not adequately accounted for clinical features that may could affect treatment response.

Researchers at the University of Michigan, the University of Washington, and Ohio State University, conducted a randomized trial with people with MS who reported clinical fatigue. They were randomized to receive telephone-based CBT, modafinil, or both therapies for 12 weeks. Fatigue effect was assessed using the Modified Fatigue Impact Scale at baseline and 12 weeks. Potential effect modifiers assessed included depression, sleep, disability level, and MS subtype. Patient Global Impression of Change score – a self-report measure of overall change in activity, symptoms, and quality of life – was also assessed.

A total of 336 participants completed the study. At 12 weeks, CBT, modafinil, and combination therapy were each linked to statistically significant and clinically meaningful MFIS score reductions. More than two-thirds of participants in each group saw at least a 10-point reduction in overall MFIS score. Sleep hygiene was an effect modifier in complete case models, in that CBT showed the greatest benefit for MFIS scores in participants with worse sleep hygiene, but statistical significance diminished after imputation for missing data. Sleepiness was associated with MFIS change scores, but effect modification was not apparent. The average PGIC score was higher for combination therapy compared to CBT or modafinil. Both CBT and modafinil were well-tolerated with infrequent discontinuation.

CBT, modafinil, and combination therapy were each linked to reduced fatigue effect in people with MS, but combination therapy was more frequently linked to perceived global benefits. Treatment effect may vary by clinical characteristics, including sleep hygiene. The researchers said MS subtype differences and treatment goals should be considered when selecting interventions, to offer a more personalized approach to management.

The study was presented at the 2023 ACTRIMS forum.