Benedetti, Fabrizio, Shaibani, Aziz · Handbook of clinical neurology · 2025 · DOI
This review article examines what we know about the placebo effect—when patients feel better simply because they believe they're receiving treatment—in several poorly understood conditions, including ME/CFS and fatigue. The authors found that most available studies on these conditions are small and lack proper comparison groups, making it impossible to draw clear conclusions about how placebo works in these illnesses. They call for more rigorous research to understand the biological mechanisms behind the placebo effect in ME/CFS and other similar conditions.
This editorial highlights a critical research gap: we lack high-quality evidence about how placebo effects operate in ME/CFS specifically. Understanding placebo mechanisms in ME/CFS is important for interpreting trial results, designing better clinical studies, and distinguishing biological disease processes from psychological factors in this complex condition.
This editorial does not prove that the placebo effect is small or large in ME/CFS, nor does it establish what proportion of ME/CFS symptoms are placebo-responsive. It is a literature review identifying existing knowledge gaps rather than a study generating new data about ME/CFS mechanisms or treatment efficacy.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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