Medications for functional dyspepsia
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First-Line Medications for Functional Dyspepsia: Proton Pump Inhibitors and Prokinetics
Proton pump inhibitors (PPIs) are widely recognized as a first-line treatment for functional dyspepsia (FD), especially for the epigastric pain syndrome (EPS) subtype. PPIs have been shown to be more effective than placebo in relieving global symptoms of dyspepsia, with similar efficacy between low and standard doses. They may also be slightly more effective than H2 receptor antagonists (H2RAs) and prokinetics, though the difference is small. PPIs are generally well tolerated, with no significant difference in adverse events compared to other treatments Yamawaki20175Miwa2022.
Prokinetic agents, such as itopride, domperidone, cisapride, and levosulpiride, are also effective, particularly for the postprandial distress syndrome (PDS) subtype. Among these, levosulpiride has shown the highest efficacy in comparative studies, outperforming several other drugs and placebo. Itopride, in long-term studies, has demonstrated sustained symptom relief and a favorable safety profile Liang2021Broeders2025Miwa2022. Acotiamide, a newer prokinetic and acetylcholinesterase inhibitor, is recommended for PDS and has shown benefit in clinical trials Yamawaki2017Miwa2022.
Neuromodulators and Antidepressants in Functional Dyspepsia
Tricyclic antidepressants (TCAs) such as amitriptyline and imipramine have established efficacy in FD, especially for patients who do not respond to first-line therapies. These medications are particularly useful for those with significant pain or visceral hypersensitivity. Antipsychotics and tetracyclic antidepressants may also be beneficial, but evidence is less robust. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) have not shown clear benefit in FD Ford2015Bosman2023Talley2010. Neuromodulators are generally considered second-line options, especially for refractory cases or when psychological factors are prominent .
Herbal and Alternative Therapies for Functional Dyspepsia
Several herbal medicines have been studied for FD. Rikkunshito, a Japanese herbal medicine, is recommended as a first-line option in Japan and has shown improvement in gastric emptying and symptoms. Other non-Chinese herbal medicines, such as STW5 (Iberogast), peppermint and caraway oil, and Curcuma longa, have demonstrated moderate efficacy in improving global symptoms of dyspepsia compared to placebo, with a generally favorable safety profile. However, the quality of evidence varies, and more high-quality studies are needed Yamawaki2017Báez2023Miwa2022.
Emerging and Investigational Therapies
Ongoing drug development for FD targets gastric motility and sensitivity. Newer prokinetics (dopamine-2 antagonists, 5-HT4 agonists), fundus relaxants (acotiamide, azapirones), and neuromodulators (guanylate cyclase and cannabinoid agonists) are under investigation. There is also interest in targeting low-grade duodenal inflammation with PPIs, histamine, and leukotriene receptor blockers. Some antibiotics, probiotics, and phytotherapeutic agents are being explored for their potential benefits .
Clinical Practice Guidelines and Treatment Approach
Current guidelines recommend a stepwise approach: starting with acid-suppressive therapy (PPIs or H2RAs) and prokinetics, followed by herbal medicines like rikkunshito. If symptoms persist, neuromodulators such as TCAs or anxiolytics may be considered. Treatment should be tailored to the FD subtype (EPS or PDS) and individual patient characteristics Yamawaki2017Miwa2022.
Conclusion
Medications for functional dyspepsia include PPIs, prokinetics (especially levosulpiride, itopride, and acotiamide), and selected neuromodulators (mainly TCAs). Herbal medicines like rikkunshito and STW5 offer additional options, particularly in certain regions. Treatment should be individualized, and ongoing research may expand future therapeutic choices Tack2019Liang2021Yamawaki2017+7 MORE.
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