CBT Plus Modafinil Effective as Monotherapy in Treating Fatigue in MS

Similar reductions in the effects of multiple sclerosis (MS)-related fatigue at 12 weeks were associated with modafinil, cognitive behavioral therapy (CBT), and a combination of both therapies, according to study findings published in Lancet Neurology.

Researchers conducted a randomized, statistician-blinded, parallel-arm, comparative effectiveness trial (COMBO-MS; ClinicalTrials.gov Identifier: NCT03612761) at the University of Washington and University of Michigan to compare the effectiveness of CBT, modafinil, and their combination in the treatment of problematic fatigue (Fatigue Severity Scale score, ≥4) that interfered with daily activities for at least 3 months in adults with MS.

Patients were randomly assigned 1:1:1 to receive CBT, modafinil, or both for 12 weeks. Multiple linear regression models were used to assess the primary outcome of mean change in Modified Fatigue Impact Scale (MFIS) from baseline to week 12.

Among the 336 participants (mean age, 48.8; women, 76%; White, 85%; non-Hispanic, 91%) with MS who were randomly assigned to treatment, 312 were included in the intent to treat analyses. Of those included in the intent to treat analyses, 114 were assigned to receive CBT, 114 were assigned to receive modafinil, and 108 were assigned to receive combination therapy.

All 3 treatment groups had clinically meaningful reductions (≥10 points) in total MFIS score at 12 weeks vs baseline. For CBT, modafinil, and combination therapy, the raw mean reductions in total MFIS scores were 15.20, 16.90, and 17.30, respectively.

No significant between-group differences were observed in terms of reductions in MFIS score. Compared with combination therapy, CBT and modafinil had an unadjusted mean difference in MFIS score change of 2.07 (95% CI, -2.33 to 6.46) and 0.42 (95% CI, -3.86 to 4.71), respectively.

In adjusted analyses, the mean difference in MFIS score change relative to the combination therapy group was 1.88 (95% CI, -2.21 to 5.96; P =.37) for the CBT group and 1.20 (95% CI, -2.83 to 5.23; P =.56) for the modafinil group.

No serious adverse events (AEs) were observed in any of the 3 treatment groups. The most commonly experienced AEs, occurring in at least 5% of participants, included insomnia, anxiety, and headache. Participants in the modafinil-containing treatment groups vs CBT treatment group more often experienced these AEs.

Study limitations include the absence of a placebo group and low number of marginalized individuals included in the sample.

“Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness,” the study authors concluded.

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.