Meta-Analysis Reveals Cognitive Behavioral Therapy Ineffective for MS-Related Fatigue

A systematic review and meta-analysis presented as a late breaker at the 2025 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 28-31, 2025, in Phoenix, Arizona, revealed that cognitive behavioral therapy (CBT) did not effectively improve fatigue severity or fatigue impact in individuals with multiple sclerosis (MS).¹

Investigators performed a comprehensive literature search and included 24 studies in their systematic review. Overall, the pooled mean change in Modified Fatigue Impact Scale (MFIS) scores for patients with MS in the CBT group was -7.77 (95% CI, -10.7 to -4.48; I² = 90%, P <.001) compared with a pooled mean change of -3.87 (95% CI, -7.52 to -0.22; I²=94%, P <.001) in the control group. Notably, the standardized mean difference (SMD) in MFIS score changes between the CBT and control groups was -3.72 (95% CI, -6.41 to -1.04; I² = 66%, P <.01).

Presented by lead author Mahsa Ghajarzadeh, MD, PhD, a post-doctoral fellow in the Department of Neurology at Johns Hopkins University School of Medicine, the pooled mean change in the CBT group for the Fatigue Severity Scale (FSS) was reported as -3.47 (95% CI, -6.12 to -0.81; I² = 87%, P <.01). In the control group, investigators noted that the pooled mean change was 2.76 (95% CI, -2.55 to 8.07; I² = 93%, P <.001). Additionally, the SMD comparing FSS score changes between the CBT and control groups was -5.63 (95% CI, -9.59 to -1.66; I² = 90%, P <.001).

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All told, the findings from the analysis suggested that CBT was not an effective treatment in improving fatigue impact and severity among patients with MS. Authors recommended that other interventions, such as consultation with an expert nurse, may help address fatigue in this patient population instead of CBT. Although this recent data questioned the efficacy of CBT for fatigue in MS, a prior meta-analysis reported moderate short-term and small long-term improvements associated with the intervention.²

In the previously published meta-analysis, researchers searched 5 databases including Cochrane Central, MEDLINE/PubMed, Embase, Emcare, and PsycINFO through July 31, 2023. Trials included in the analysis had to compare CBT with another intervention or usual care and assess fatigue as a primary outcome. Authors noted that most studies were considered to have a low overall risk of bias, though CBT protocols varied by delivery method, session frequency, duration, and therapist.

Published in Multiple Sclerosis and Related Disorders, researchers included 8 randomized controlled trials assessing CBT in adults with MS and fatigue. Among these studies, 6 contributed to a pooled analysis, which showed significant reductions in fatigue severity and impact both in the short term (SMD, -0.58; 95% CI, -0.85 to -0.31; P <.0001) and long term (SMD -0.36; 95% CI, -0.52 to -0.19; P <.0001). The short-term evidence was rated as low certainty because of heterogeneity and potential publication bias, whereas the long-term result was supported by high-certainty evidence.

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REFERENCES
1. Ghajarzadeh M, Rastkar M, Pourshams M. The Effects of Cognitive Behavioral Therapy (CBT) on Fatigue Impact and Severity in Patients with Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis. Presented at: 2025 CMSC Annual Meeting; May 28-31; Phoenix, AZ. ABSTRACT LBA08.
2. Vo HLT, Elias S, Hardy TA. Cognitive behavioural therapy for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord. 2024;91:105908. doi:10.1016/j.msard.2024.105908