Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review and Component Network Meta‐Analysis

OBJECTIVE: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating condition characterized by persistent fatigue, impaired functioning, and substantial societal burden. Although cognitive behavioral therapy (CBT) is commonly used for CFS/ME, the effective components and delivery formats remain unclear. METHODS: We systematically searched MEDLINE, Embase, PsyclNFO, Web of Science, the Cochrane Library, and major English and Chinese databases from inception to January 15, 2025, without language restrictions. Ultimately, a frequentist network meta-analysis (NMA) and component network meta-analysis (cNMA) of 16 randomized controlled trials were conducted to assess the associations between CBT components, delivery formats, and patient-important outcomes. RESULTS: At the treatment level, guided self-help CBT (mean difference [MD], -6.89; 95% CI, -9.56 to -4.22; moderate certainty) and individual CBT (MD, -4.81; 95% CI, -6.98 to -2.65; moderate certainty) probably reduced fatigue when measured immediately after treatment. At the component level, goal setting (incremental mean difference [iMD], -8.83; 95% CI, -16.92 to -0.74), third-wave components (iMD, -6.02; 95% CI, -11.33 to -0.72), and cognitive restructuring (iMD, -4.41; 95% CI, -8.83 to 0.01) were associated with reduced fatigue when measured immediately after treatment. Psychoeducation was potentially counterproductive (iMD, 5.23; 95% CI, 0.64 to 9.82). At the end of follow-up, cognitive restructuring was associated with reduced fatigue and depression, and improved physical function; goal setting was also associated with improved physical function. The combination of goal setting, third-wave components, and cognitive restructuring delivered via guided self-help may be an efficacious component-based intervention relative to the nonspecific treatment component (iMD, -16.33; 95% CI, -26.68 to -5.99). CONCLUSIONS: The effective CBT combination probably involves goal setting, third-wave components, and cognitive restructuring delivered via guided self-help, while psychoeducation may be detrimental. Future studies should prospectively examine core CBT components and their interactions, as well as incorporate measures of dose and intensity to guide more personalized and scalable interventions. TRIAL REGISTRATION: CRD420251018083.