#3-24E. Redefining the Functional: Microinflammation and Management in Dyspepsia (NEJM, 2026)

How do you manage patients with persistent epigastric pain when endoscopy is normal and proton-pump inhibitors fail? This review in the New England Journal of Medicine redefines Functional Dyspepsia (FD) not merely as a disorder of gut-brain interaction, but as a heterogeneous syndrome potentially driven by duodenal microinflammation and aberrant Th2 immune responses. The authors detail the significant symptom overlap with IBS and GERD, emphasizing that while acid suppression is first-line, no specific drug is currently approved for FD. The most critical clinical takeaway is the evidence supporting low-dose tricyclic antidepressants, specifically amitriptyline, which demonstrated efficacy in achieving adequate relief, particularly for epigastric pain. However, when appraising this literature, one must recognize that the persistence of "functional" as a broad umbrella term remains a limitation, creating diagnostic ambiguity that may mask distinct neurogastrointestinal pathologies and complicate trial homogeneity. For the practicing physician, this paper is vital because it legitimizes the biological basis of FD and provides a structured, empirical pharmacologic strategy—moving beyond acid suppression to neuromodulation—for treating a high-burden patient population often dismissed as having "nothing wrong."

Citation: Pasricha PJ, Talley NJ. Functional Dyspepsia. N Engl J Med. 2026. DOI: 10.1056/NEJMcp2501860

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