Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Observed Findings

• Eight different case definitions for ME/CFS are in use, with ME criteria (requiring postexertional malaise) identifying a more symptomatic subset than broader ME/CFS criteria.
• Rintatolimod improved measures of exercise performance compared to placebo.
• Counseling therapies and graded exercise therapy improved fatigue, function, quality of life, and employment outcomes compared to no treatment or standard care.
• Graded exercise therapy was associated with higher reported adverse events than counseling therapies or control conditions.
• Adverse events and harms were generally inadequately reported across treatment trials.

Inferred Conclusions

• No current diagnostic method has been adequately validated for identifying ME/CFS in populations with diagnostic uncertainty.
• Counseling therapies and graded exercise have broader demonstrated benefit than other treatments, but evidence is limited to less disabled populations.
• Significant research gaps exist in both diagnostic accuracy studies and treatment trials, limiting clinical confidence in current approaches.
• More rigorous, larger-scale studies with standardized diagnostic criteria and thorough adverse event reporting are essential for advancing ME/CFS care.

Remaining Questions