Functional dyspepsia
Chronic symptom complex of epigastric pain or postprandial fullness without identified organic cause on workup. Diagnosed by the Rome IV criteria.
ICD-10 K309 drugs
Also known as: Non-ulcer dyspepsia
Drugs used for this condition
- AEsomeprazoleFirst line · Drugs for peptic ulcer and GORD. Proton pump inhibitorsEsomeprazole is a proton pump inhibitor, and PPIs are first-line for functional dyspepsia (ACG/CAG 2017). Cochrane confirms a PPI advantage over placebo (NNT about 11), and esomeprazole has positive RCTs. Use a short course with review at 4 to 8 weeks; with alarm features (weight loss, dysphagia, bleeding, new onset over age 50) endoscopy comes first. Long-term use without an indication is undesirable.
- BChamomile (Matricaria chamomilla / recutita, flowers)Add-on therapy · Herbal preparation, EMA HMPC traditional herbal medicinal productChamomile is one of the best-evidenced herbal options for functional dyspepsia and mild GI spasm. EMA HMPC in 2015 granted chamomile flowers well-established-use status for symptomatic treatment of mild gastrointestinal disturbances: flatulence, spasm and mild dyspepsia. Chamomile is part of Iberogast – a combined herbal product with RCT-proven efficacy in functional dyspepsia. Per Rome IV criteria, diagnosis rests on post-prandial fullness, early satiety and epigastric pain without organic pathology. Taking 1.5–3 g of dried flowers as tea three times a day or an equivalent extract for 2–4 weeks is a reasonable first step. If symptoms persist beyond a month, or weight loss, haematemesis or melaena appear, gastroscopy is needed, not herbal tea.
- CAlmagateAdd-on therapy · Antacid (aluminium magnesium hydroxide carbonate)Symptomatic relief of epigastric pain and discomfort in functional dyspepsia. Per Rome IV and dyspepsia management guidelines (ACG/CAG 2017; GuíaSalud/AEG-semFYC), first-line depends on subtype: PPIs for epigastric pain syndrome; prokinetics for postprandial distress. Antacids give quick relief but do not modify disease course.
- CCinitaprideSecond line · Benzamide prokinetic with combined serotonin and dopamine receptor activityIn functional dyspepsia, cinitapride is used symptomatically when postprandial distress predominates. Evidence is modest: Spanish and Latin American trials showed symptom reduction versus placebo, but large independent meta-analyses are absent. International guidelines (Rome IV, ACG 2022) do not list it as a preferred agent – first-line is a PPI and Helicobacter pylori eradication.
- CMastic gumAdd-on therapy · Over-the-counter botanical supplement, the resin of Pistacia lentiscus var. Chia (Chios mastic), cultivated on the island of Chios in Greece; marketed for functional dyspepsia and H. pyloriMastic gum is an over-the-counter botanical supplement with traditional use for mild dyspepsia. EMA HMPC 2015 included Pistacia lentiscus in a community herbal monograph as a traditional use product for symptomatic relief of mild dyspepsia and superficial skin inflammation. A small RCT by Kottakis (J Ethnopharmacol 2008) in 60 patients with dyspepsia showed an improved symptom score after 4 weeks of 350 mg mastic three times daily. The sample is small with no PPI comparison. Per Rome IV 2016 and ACG 2017 functional dyspepsia is a diagnosis of exclusion after H. pylori testing and alarm symptom assessment; standard care is H. pylori test-and-treat (Maastricht VI 2022), empirical PPI for 4–8 weeks and a prokinetic in post-prandial distress. Mastic is not mentioned as an option in the guidelines. If mastic is considered as a mild adjunct alongside a PPI, discuss with a gastroenterologist – it is well tolerated but does not stand in for standard therapy.
- CMelissa officinalis (leaf extract)Add-on therapy · Herbal sedative, EMA HMPC traditional herbal medicinal productLemon balm is part of combined herbal products (Iberogast and analogues) with a confirmed effect in functional dyspepsia – post-prandial fullness, early satiety and epigastric pain per Rome IV criteria. Lemon balm essential oils relax intestinal smooth muscle and ease spasm. EMA HMPC separately recognises lemon balm for mild GI cramps. In monotherapy lemon balm has scarce data – clinical benefit is mainly proven for combined formulations. Taking 1–2 g of dried herb or an equivalent extract 2–3 times daily for 2–4 weeks is acceptable for mild symptoms. If symptoms persist beyond a month or come with weight loss, vomiting or blood in stool, gastroscopy is needed, not herbs.
- DTrimebutineSecond line · GI motility regulator, peripheral opioid receptor agonistIn functional dyspepsia, trimebutine did not show benefit over placebo in large trials. Used as an add-on when dyspepsia coexists with motility disturbance.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- CDeglycyrrhizinated licorice (DGL)Not recommended · Over-the-counter botanical supplement, an extract of Glycyrrhiza glabra root with glycyrrhizin removed (to eliminate the mineralocorticoid effect); marketed for peptic ulcer, functional dyspepsia and H. pyloriIn functional dyspepsia DGL was studied in one larger RCT. Raveendra (2012) tested GutGard (a standardized licorice root extract) in 50 patients with functional dyspepsia: 30 days of 150 mg/day improved the overall symptom score versus placebo. This is a small sample, single center, short follow-up. EMA HMPC 2012 recognizes only traditional use of licorice root for dyspepsia. No Cochrane review of DGL in functional dyspepsia exists. Rome IV 2016 and ACG 2017 frame functional dyspepsia as a diagnosis of exclusion after H. pylori testing (Maastricht VI 2022, AEG 2022) and alarm-symptom assessment; therapy includes H. pylori test-and-treat, empirical PPI for 4–8 weeks, prokinetic for post-prandial distress and low-dose TCA or SSRI if needed. DGL is not mentioned in the guidelines. If DGL is considered as an add-on to PPI or prokinetic, discuss with a gastroenterologist – mild cytoprotection is plausible but not first-line therapy.
- DBetaine hydrochlorideNot recommended · Over-the-counter supplement, an acidic salt of betaine (trimethylglycine hydrochloride); marketed as a gastric acid replacement for «low stomach acid»; commonly combined with pepsin on iHerb and AmazonBetaine hydrochloride is an OTC supplement marketed for «low stomach acid» as a cause of bloating, post-meal fullness and belching. The actual evidence is limited: the pH study by Yago (Mol Pharm 2013) in 6 healthy volunteers shows brief local gastric acidification after drug-induced hypochlorhydria, but no clinical RCTs in functional dyspepsia with a symptom-relief endpoint exist. Per Rome IV 2016 and ACG 2017, functional dyspepsia is a diagnosis of exclusion after assessment of alarm symptoms and H. pylori testing (Maastricht VI 2022, AEG 2022). Standard care: H. pylori test-and-treat, empirical PPI for 4–8 weeks, prokinetic for post-prandial distress. The FDA in 1993 removed betaine HCl from the OTC monograph. AEMPS and AESAN treat the product as a complemento alimenticio without therapeutic indication. If betaine HCl was bought «for digestion», discuss symptoms with a gastroenterologist – prescribing a stomach-acid replacement blind, without workup, is not justified.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit