Lancet Neurol

Fatigue in MS: Comparing drugs, cognitive behavioral therapy, and combined treatment

October 30, 2024

Modafinil, cognitive behavioral therapy (CBT), and combination treatment all showed similar benefits in multiple sclerosis-related fatigue at 12 weeks, in this comparative effectiveness trial. Combination therapy didn’t augment the improvement over individual interventions. Further research is warranted to determine whether these results are influenced by sleep-related issues.

• This trial at 2 U.S. centers randomized 336 adults with MS and problematic fatigue (Fatigue Severity Scale [FSS] score 4+) to modafinil, CBT, or both for 12 weeks. While the statisticians were masked to group assignment, participants, neurologists, and CBT providers weren’t masked.
• Primary outcome was a change in the Modified Fatigue Impact Scale (MFIS) at 12 weeks, adjusted for age, sex, anxiety, pain, baseline MFIS, physical activity, and other factors.
• At week 12, modafinil, CBT, and combination groups all showed clinically meaningful MFIS reductions; the MFIS change from baseline didn’t differ between groups. Combination therapy wasn’t superior to each individual treatment.
• The most common adverse events for those on modafinil were insomnia (7% for modafinil, 7% for combination treatment) and anxiety (3% for modafinil, 8% for combination treatment).

Source:

Braley TJ, et al. (2024, November). Lancet Neurol. Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial. https://pubmed.ncbi.nlm.nih.gov/39424559/