Functional Dyspepsia
Pankaj J. Pasricha and Nicholas J. Talley
Summary
Functional dyspepsia is a common but serious medical syndrome that can induce weight loss and food aversion and may be associated with increased risks of hospitalization and death. It probably comprises several different and as yet incompletely characterized disorders. Patients with local mucosal microinflammation driven by an aberrant Th2 response may represent an important subgroup. There is overlap with other gastrointestinal syndromes, particularly irritable bowel syndrome and gastroesophageal reflux disease, and patients with overlap have more severe symptoms. There is no approved drug for functional dyspepsia. Treatment is empirical and directed at symptoms and consists of acid suppressants and low-dose tricyclic antidepressants (and other neuromodulators) along with appropriate nutritional and psychological support.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations.
A 33-year-old woman presents with a 3-year history of epigastric burning pain, nausea, and early satiety after meals. She is increasingly anxious because endoscopy and imaging have not found any underlying cause, and she has not had a response to omeprazole or over-the-counter medications. How would you further evaluate and treat this patient?
The Clinical Problem
Functional dyspepsia is a syndrome of unexplained epigastric pain or burning, postprandial fullness, or meal-restricting early satiety (and often bloating and nausea) in varying combinations. Worldwide, functional dyspepsia is present in 7.2% of adults (10.1% in the United States), affects women 1.6 times as often as men, and is more common in persons younger than 40 years of age.1 The incidence of functional dyspepsia is estimated to be 3 to 4% per year.2
Key Points
Functional dyspepsia is a common but serious medical syndrome that can induce weight loss and food aversion and may be associated with increased risks of hospitalization and death.
The syndrome probably comprises several different and as yet incompletely characterized disorders; local microinflammation driven by an aberrant response by type 2 helper T cells may represent an important subset of cases.
Functional dyspepsia can overlap with other gastrointestinal syndromes, particularly irritable bowel syndrome and gastroesophageal reflux disorder, and persons with such overlap have more severe symptoms.
There is no approved drug therapy; treatment is empirical and directed at symptoms, consisting of acid suppressants and low-dose tricyclic antidepressants (and other neuromodulators), along with appropriate nutritional and psychological support.
| Drug Class | Pathophysiological Target | Examples | Relative Strength of Evidence |
|---|---|---|---|
| Acid suppressants | Acid-induced reflexes triggered by enteric and sensory neurons | Proton-pump inhibitor, H2RA | |
| Neuromodulators | Increased or aberrant signaling by afferent neurons to the CNS | Tricyclic antidepressants, duloxetine, mirtazapine, pregabalin, gabapentin |
Symptom abatement with low-dose tricyclic antidepressant: relative risk of no improvement, 0.75 (95% CI, 0.62 to 0.90)27
No placebo-controlled trials of duloxetine; not as efficacious as nortriptyline for functional dyspepsia symptoms but better with regard to anxiety, depression, and quality of life30
Pregabalin: relative risk of no improvement with pregabalin, 0.53 (95% CI, 0.29 to 0.96)31
|
| Motility agents† | Delayed gastric emptying, decreased gastric accommodation | Metoclopramide, domperidone, prucalopride, buspirone | Controlled trials of metoclopramide, domperidone, and prucalopride are lacking; buspirone (three small trials of 4-wk duration) led to nonsignificant improvement in functional dyspepsia and gastroparesis symptoms vs. placebo (standardized mean difference, –0.14; 95% CI, –0.44 to 0.17; P=0.39); with regard to individual symptoms, buspirone reduced only the severity of bloating more than placebo32 |
| Th2 response modulators | Eosinophil and mast-cell activation | Montelukast, mast-cell antagonists (H1RA, H2RA, ketotifen) | Evidence limited to children only32; no evidence for mast-cell antagonists |
| Agents affecting the microbiota | Dysbiosis | Bacillus coagulans and B. subtilis combination, rifaximin | Limited evidence: single trials, small numbers, and short-term results |
| Over-the-counter remedies | Miscellaneous | Peppermint-oil preparations | Limited evidence: few trials, small numbers, and short-term results |
*
CNS denotes central nervous system, H1RA histamine H1–receptor antagonist, H2RA histamine H2–receptor antagonist, and Th2 type 2 helper T.
†
Shown are agents that are available in the United States.
