Modafinil and talk therapy are both useful for easing MS fatigue: Study
COMBO-MS enrolled 336 adults whose fatigue interfered with daily activities
Treatment with modafinil, a medication used to reduce excessive sleepiness, and cognitive behavioral therapy (CBT) can both provide clinically meaningful reductions in fatigue in people with multiple sclerosis (MS), a new study reports.
Combining modafinil with CBT, a form of talk therapy, wasn’t more effective for MS-related fatigue than either intervention on its own, the results suggest however.
“These data suggest that modafinil and CBT, either as monotherapy [on its own] or combination therapy, should be considered as potential treatment options for people with multiple sclerosis with chronic problematic fatigue,” wrote the researchers, who said the decision about which treatment to use can be guided by patient preference and other factors.
The study, “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,” was published in The Lancet Neurology.
Fatigue, which is a feeling of tiredness and low energy that persists even when a person is rested, is one of the most common and debilitating symptoms of MS.
Both modafinil, a wakefulness-promoting medicine sold as Provigil, among others, and CBT have been individually studied with some positive results to help combat MS-related fatigue. It’s not clear how the two interventions compare or if combining them nets better results, however.
“Both CBT and modafinil have been shown to reduce symptoms of fatigue, but we didn’t really know which one works better, which works best for which patients, and whether combining the two might have a better effect than we get when we only used one or the other,” Kevin Alschuler, PhD, study co-author at the University of Washington, said in a university news story.
Medicine, talk therapy for fatigue
To find out, the University of Michigan sponsored a clinical trial called COMBO-MS (NCT03621761) that enrolled 336 adults with MS-related fatigue that had been interfering with their daily activities for at least three months. Each participant was randomly assigned to one of three interventions — modafinil, CBT, or both modafinil and CBT in combination — for 12 weeks. Modafinil was taken at doses that ranged from 50-400 mg a day, based on the patients’ needs. CBT is designed to aid in breaking unhelpful thought patterns and participants assigned to this treatment received eight weekly therapy sessions, followed by two maintenance sessions given two weeks apart.
The trial’s main goal was to assess changes in fatigue after 12 weeks, which was monitored before and after the interventions using a standardized scale called the Modified Fatigue Impact Scale (MFIS). An improvement of at least 10 points on the MFIS is considered clinically meaningful.
“Fatigue is one of the most common and debilitating symptoms of multiple sclerosis, yet there is still uncertainty about how available treatments should be used or how medication-based treatments compare to behavioral treatments in the real world,” Tiffany J. Braley, MD, first author of the study at the University of Michigan, said in a separate university news release.
All three interventions led to significant improvements in MFIS scores, which improved on average by 15.2 points with modafinil, 16.9 points with CBT, and 17.3 points with the combination. About two-thirds of the patients in each group reported clinically meaningful MFIS gains.
Statistical analyses showed no significant differences in the amount of fatigue improvement between the groups, but CBT seemed to work best in those with poor sleep habits, such as not going to bed at a consistent time, whereas modafinil was more effective for those with good sleep habits.
“Those with poor sleep habits had better outcomes with CBT, while those with good sleep habits did better with modafinil,” Alschuler said. “The finding suggests that if you have a patient who could improve their behavior around sleep, CBT might be best to try first, while if you have a patient who already has good sleep habits, you might try modafinil first.”
No serious safety issues were reported for modafinil, CBT, or the combination. The most common side effects with the medication were insomnia, anxiety, and headache.
The results indicate “each treatment offers largely equivalent, clinically meaningful benefits for the effects of multiple sclerosis fatigue in people with multiple sclerosis, with high acceptance, good adherence, and good tolerability,” wrote the researchers, who emphasized that decisions about whether to use modafinil, CBT or both should be made on a case-by-case basis depending on each patient’s specific needs and desires.
“This study focused intently on patient-centered outcomes and our findings highlight the importance of shared decision making about treatment selection, with consideration of patient characteristics and broader treatment goals,” Braley said.
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