EFFECTIVENESS OF THERAPEUTIC INTERVENTIONS FOR CHRONIC FATIGUE SYNDROME: A NARRATIVE REVIEW

Abstract

Background Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a heterogeneous disorder characterized by persistent fatigue, post-exertional malaise, unrefreshing sleep, pain, cognitive symptoms, and impaired daily functioning. Diagnosis is based on clinical criteria and exclusion of other diseases, while reliable biomarkers and standard treatment are lacking. Aims This narrative review aimed to summarize the reported effects of cognitive behavioral therapy, exercise-based interventions, nutritional supplementation, rituximab, and rintatolimod in patients with CFS. Materials and Methods A structured narrative literature search was performed in PubMed and Google Scholar. ResearchGate was used only to retrieve full-text articles. The search was conducted in June 2026 and covered publications from 2001 to 2025. Of 132 identified publications, 54 were included. Because the studies differed in design, diagnostic criteria, interventions, follow-up duration, and outcome measures, the evidence was synthesized qualitatively. Results Cognitive behavioral therapy appeared to show the most consistent beneficial effects, mainly on fatigue and physical functioning, although complete recovery was uncommon. Exercise-based interventions produced mixed results; self-paced aquatic exercise programs were better tolerated, whereas graded exercise did not consistently outperform comparator interventions and was associated with symptom worsening in some patients. Nutritional interventions showed heterogeneous findings, with reported benefits mainly for CoQ10 plus NADH, selenium, creatine, and combined nutraceutical therapy. Rituximab did not show efficacy in a phase III randomized trial. Rintatolimod showed promising effects on exercise tolerance, but further confirmation is required. Conclusions Cognitive behavioral therapy may help reduce symptoms and improve functioning in selected patients with CFS, but it should not be presented as curative. Exercise programs should be individualized and adapted to the risk of post-exertional malaise. Nutritional supplementation may have an adjunctive role, but evidence remains heterogeneous. Rituximab cannot be recommended for routine use, while rintatolimod remains investigational. Future studies should clarify which patient subgroups may benefit from specific interventions.