Fatigue is one of the most common debilitating symptoms of MS, affecting up to 80% of patients and significantly disrupting their daily lives. However, the underlying mechanism remains unknown. CBT is a well-known therapy for Psychological symptoms of MS. Many programs have been developed to manage fatigue, CBT is an Essential component.

We searched online databases such as PubMed, Cochrane Library, Scopus, and Web of Science until September 2024 for studies that matched the eligibility criteria, any clinical trials that utilized CBT programs as an intervention, and any fatigue scales as an outcome focusing on participants aged 18 years or older. We excluded all trials involving pharmacological therapy, case reports, or reviews. We assessed the risk of bias using ROB-2 for RCTs and ROBINS-I for nRCTs. The primary outcomes were the Modified Fatigue Impact Scale (MFIS), Chalder Fatigue Scale (CIS), and Fatigue Severity Scale (FSS). Secondary outcomes included the MS Quality of Life (MSQOL) and Short Form Health Survey (SF-36). Outcomes were qualitatively reviewed, and a meta-analysis was performed using standardized mean difference (SMD) with 95% confidence intervals (CIs) calculated using Review Manager (RevMan).

Seven RCTs matched the inclusion criteria. Four of these (324 participants) were eligible for the analysis. The overall effect estimate showed that CBT was significantly superior to the standard therapy in terms of fatigue scales (SMD = -0.4, 95% CI [-0.62 -0.18], P = 0.0004). and quality of life (SMD = 0.26, 95% CI [0.00, 0.51], P = 0.05). 

CBT programs can effectively reduce MS-associated fatigue and maintain their effects for at least 12 months. Nonetheless, they can improve the quality of life compared to standard therapy.