Indigestion

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Indigestion
Other names: Dyspepsia, upset stomach
Location of the upper abdomen, also known as the epigastrium
SpecialtyGastroenterology
SymptomsUpper abdominal discomfort, heartburn, reflux[1][2]
CausesGERD, gastritis, peptic ulcer disease, esophageal spasm, delayed gastric emptying, lactose intolerance, coronary artery disease, cancer[3]
Diagnostic methodResting for H. pylori, endoscopy[1]
PreventionAvoiding smoking, alcohol, coffee, chocolate, fatty foods, and being overweight[2]
TreatmentAntacids, proton pump inhibitors, H2 receptor antagonists[2][4]
FrequencyCommon[1]

Indigestion, also known as dyspepsia or upset stomach, is the symptoms of upper abdominal discomfort, heartburn, or reflux.[2] It may also include abdominal fullness, nausea, belching, and feeling full earlier than expected when eating.[5][6] These symptoms are often long-term or recurrent.[6] It may decrease quality of life.[1]

Causes may include gastroesophageal reflux disease (GERD), gastritis, peptic ulcer disease, esophageal spasm, delayed gastric emptying, lactose intolerance, coronary artery disease, and cancer.[3] A number of medications may also causes problems including NSAIDs, bisphosphonates, and corticosteroids.[2] Functional indigestion may be diagnosed when there are symptoms but no evidence of underlying disease.[3]

In people over the age of 60 or with worrisome symptoms such as trouble swallowing, weight loss, or low red blood cells, endoscopy (a procedure where a camera on a flexible tube is inserted down the throat to the stomach) is recommended to assess potential causes.[1] In people under 60, testing for the bacteria H. pylori and if positive, treatment is recommended.[1] In Asia endoscopy is recommended in those over 35 years old.[1]

Measures that may help include avoiding smoking, alcohol, coffee, chocolate, fatty foods, and being overweight.[2] Not eating just before bed and raising the head of the bed may also help.[2] Often antacids help, while the addition of viscous lidocaine is of unclear benefit.[4] Proton pump inhibitors are often used, and H2 receptor antagonists may be added to this.[2]

Indigestion is common, affecting about 20% of people at some point during their life.[1] Functional indigestion makes up the majority of cases in Western countries, affecting about 15% of people.[7][8] Indigestion is not associated with a decrease in life expectancy. [1] The term is from the Greek "dys" meaning "bad" and "pepse" meaning "digestion".[5] Desciptions of the condition date from the 18th century.[5]

Signs and symptoms

People experiencing indigestion likely report one, a combination of, or all of the following symptoms:[9][10]

There may be abdominal tenderness, but this finding is nonspecific and is not required to make a diagnosis.[10] However, there are physical exam signs that may point to a different diagnosis and underlying cause for a patient's reported discomfort. A positive Carnett sign (focal tenderness that increases with abdominal wall contraction and palpation) suggests an etiology involving the abdominal wall musculature. Cutaneous dermatomal distribution of pain may suggest a thoracic polyradiculopathy. Tenderness to palpation over the right upper quadrant, or Murphy's sign, may suggest cholecystitis or gallbladder inflammation.[11]

Worrisome symptoms

Also known as alarm features, alert features, red flags, or warning signs. Alarm features are thought to be associated with serious gastroenterologic disease and include:[12]

Cause

Indigestion is a diagnosis related to a combination of symptoms that can be attributed to organic or functional causes.[13] Organic dyspepsia has findings upon endoscopy, like an ulcer in the stomach lining in peptic ulcer disease.[13] Functional dyspepsia has a normal endoscopy and can be broken down into two subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS).[14] In addition, indigestion could be caused by medications, food, or other disease processes.

Psychosomatic and cognitive factors are important in the evaluation of people with chronic dyspepsia. Studies have show a high occurrence of mental disorders, notably anxiety and depression, amongst patients with dyspepsia; however, there is little evidence to prove causation.[15]

Esophagitis

Esophagitis is an inflammation of the esophagus, most commonly caused by gastroesophageal reflux disease (GERD).[9] It is defined by the sensation of "heartburn" or a burning sensation in the chest as a result of inappropriate relaxation of the lower esophageal sphincter at the site where the esophagus connects to the stomach. It is often treated with proton pump inhibitors. If left untreated, the chronic damage to the esophageal tissues poses a risk of developing cancer.[9] A meta-analysis showed risk factors for developing GERD included age equal to or greater than 50, smoking, the use of non-steroid anti-inflammatory medications, and obesity.[16]

Gastritis

Common causes of gastritis include peptic ulcer disease, infection, or medications.

Peptic ulcer disease

Gastric and/or duodenal ulcers are the defining feature of peptic ulcer disease (PUD). PUD is most commonly caused by an infection with H. pylori or NSAID use.[17]

Helicobacter pylori

The role of H. pylori in functional dyspepsia is controversial, and treatment for H. pylori may not lead to complete improvement of dyspepsia.[9] A review in 2022 suggests that successful treatment of H. pylori modestly improves indigestion symptoms.[18]

Pancreatobiliary disease

These include cholelithiasis, chronic pancreatitis, and pancreatic cancer.

Functional dyspepsia

Functional dyspepsia is a common cause of chronic heartburn. More than 70% of people have no obvious organic cause for their symptoms after evaluation.[13] It was previously called nonulcer dyspepsia.[7] Symptoms may arise from a complex interaction of increased visceral afferent sensitivity, gastric delayed emptying (gastroparesis) or impaired accommodation to food. Diagnostic criteria for functional dyspepsia categorize it into two subtypes by symptom: epigastric pain syndrome and post-prandial distress syndrome.[14] Anxiety is also associated with functional dyspepsia. In some people, it appears before the onset of gut symptoms; in other cases, anxiety develops after onset of the disorder, which suggests that a gut-driven brain disorder may be a possible cause.[14] Although benign, these symptoms may be chronic and difficult to treat.[19] Duodenal micro-inflammation caused by an altered duodenal gut microbiota, reactions to foods (mainly gluten proteins) or infections may induce dyspepsia symptoms in a subset of people.[20]

It contains to subtypes epigastric pain syndrome defined by stomach pain or burning that interfers with daily life, without any evidence of organic disease.[21]

And post-prandial distress syndrome defined by post-prandial fullness or early satiation that interfers with daily life, with any evidence of organic disease.[21]

Food or drug intolerance

Acute, self-limited dyspepsia may be caused by overeating, eating too quickly, eating high-fat foods, eating during stressful situations, or drinking too much alcohol or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), bronchodilators (theophylline), diabetes drugs (acarbose, metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin converting enzyme [ACE] inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine oxidase [MAO]-B inhibitors), weight-loss medications (orlistat), corticosteroids, estrogens, digoxin, iron, and opioids.[22][23] Common herbs have also been show to cause indigestion, like white willow berry, garlic, ginkgo, chaste tree berry, saw palmetto, and feverfew.[22] Studies have shown that wheat and dietary fats can contribute to indigestion and suggest foods high in short-chain carbohydrates (FODMAP) may be associated with dyspepsia.[24] This suggests reducing or consuming a gluten-free, low-fat, and/or FODMAP diet may improve symptoms.[24][25] Additionally, some people may experience dyspepsia when eating certain spices or spicy food as well as foods like peppers, chocolate, citrus, and fish.[9]

Systemic diseases

There are a number of systemic diseases that may involve dyspepsia, including coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, and chronic kidney disease.

Post-infectious

Gastroenteritis increases the risk of developing chronic dyspepsia. Post-infectious dyspepsia is the term given when dyspepsia occurs after an acute gastroenteritis infection. It is believed that the underlying causes of post-infectious IBS and post-infectious dyspepsia may be similar and represent different aspects of the same pathophysiology.[26]

Pathophysiology

The pathophysiology for indigestion is not well understood; however, there are many theories. For example, there are studies that suggest a gut-brain interaction, as patients who received an antibiotic saw a reduction in their indigestion symptoms.[27] Other theories propose issues with gut motility, a hypersensitivity of gut viscera, and imbalance of the microbiome.[8] A genetic predisposition is plausible, but there is limited evidence to support this theory.[28]

Diagnosis

Diagram of how indigestion is diagnosed and treatment determined

A diagnosis for indigestion is based on symptoms, with a possible need for more diagnostic tests. In younger patients (less than 60 years of age) without red flags (e.g., weight loss), it is recommended to test for H. pylori noninvasively, followed by treatment with antibiotics in those who test positively. A negative test warrants discussing additional treatments, like proton pump inhibitors, with your doctor.[1] An upper GI endoscopy may also be recommended.[29] In older patients (60 or older), an endoscopy is often the next step in finding out the cause of newly onset indigestion regardless of the presence of alarm symptoms.[1] However, for all patients regardless of age, an official diagnosis requires symptoms to have started at least 6 months ago with a frequency of at least once a week over the last 3 months.[10]

Treatment

Functional and organic dyspepsia have similar treatments. This includes lifestyle modification (e.g., diet), antacids, proton-pump inhibitors (PPIs), H2-blockers, prokinetics, and antiflatulents. PPIs and H2-blockers are often first-line, having shown to be better than placebo.[30] Anti-depressants, notably tricyclic antidepressants, have also been shown to be effective treatments for people who do not respond to traditional therapies.[30]

Diet

A change in diet, such as a stable and consistent eating schedule and slowing the pace of eating may help.[31] Additionally, there is support to reduce fats.[31] While some studies suggest a correlation between dyspepsia and celiac disease, not everyone with indigestion needs to refrain from gluten in their diet. However, a gluten-free diet can relieve the symptoms in some without celiac disease.[20][31] Lastly, a FODMAPs diet or diet low/free from certain complex sugars and sugar alcohols has also been show to be potentially beneficial in indigestion.[31]

Acid suppression

Proton pump inhibitors (PPIs) are effective, especially when looking at long-term symptom reduction.[32][33] H2 receptor antagonists (H2-RAs) have similar effect on symptoms reduction when compared to PPIs.[32] However, there is little evidence to support prokinetic agents are an appropriate treatment for dyspepsia.[34]

Currently, PPIs are FDA indicated for erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia.[35]

Prokinetics

Prokinetics (medications focused on increasing gut motility), such as metoclopramide or erythromycin, has a history of use as a secondary treatment for dyspepsia.[9] While studies show that it is more effective than placebo, there are multiple concerns about the side effects with long-term use.[9]

Alternative medicine

A 2021 meta-analysis concluded that herbal remedies, like menthacarin (a combination of peppermint and caraway oils), ginger, artichoke, licorice, and jollab (a combination of rose water, saffron, and candy sugar), may be as beneficial as conventional therapies when treating dyspepsia symptoms.[36] However, as not regulated it is difficult to assess the quality and safety of the ingredients found in alternative medications.[37]

Epidemiology

Indigestion is a common problem and frequent reason for primary care physicians to refer patients to GI specialists.[38] Worldwide, dyspepsia affects about a third of the population.[39] It can affect a person's quality of life even if the symptoms within themselves are usually not life-threatening. Additionally, the financial burden on the patient and healthcare system is costly - patients with dyspepsia were more likely to have lower work productivity and higher healthcare costs compared to those without indigestion.[40] Risk factors include NSAID-use, H. pylori infection, and smoking.[41]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Eusebi, Leonardo H; Black, Christopher J; Howden, Colin W; Ford, Alexander C (11 December 2019). "Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis". BMJ. 367: l6483. doi:10.1136/bmj.l6483. PMC 7190054. PMID 31826881.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Recommendations | Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management | Guidance | NICE". www.nice.org.uk. 3 September 2014. Archived from the original on 21 May 2023. Retrieved 19 June 2023.
  3. ↑ 3.0 3.1 3.2 "Dyspepsia - Gastrointestinal Disorders". Merck Manuals Professional Edition. Archived from the original on 23 March 2023. Retrieved 19 June 2023.
  4. ↑ 4.0 4.1 Ton, Joey (3 May 2021). "#289 Keeping it Simple for Emergency Room Dyspepsia". CFPCLearn. Archived from the original on 1 July 2023. Retrieved 15 June 2023.
  5. ↑ 5.0 5.1 5.2 Schmidt-Martin, Daniel; Quigley, Eamonn M. M. (2011). "1. The definition of dyspepsia". In Duvnjak, Marko (ed.). Dyspepsia in clinical practice (1. Aufl. ed.). New York: Springer. p. 2. ISBN 9781441917300. Archived from the original on 2023-01-10. Retrieved 2022-03-28.
  6. ↑ 6.0 6.1 Talley NJ, Vakil N (October 2005). "Guidelines for the management of dyspepsia". Am. J. Gastroenterol. 100 (10): 2324–37. doi:10.1111/j.1572-0241.2005.00225.x. PMID 16181387. S2CID 16499689.
  7. ↑ 7.0 7.1 Saad RJ, Chey WD (August 2006). "Review article: current and emerging therapies for functional dyspepsia" (PDF). Aliment. Pharmacol. Ther. 24 (3): 475–92. doi:10.1111/j.1365-2036.2006.03005.x. hdl:2027.42/74835. PMID 16886913. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  8. ↑ 8.0 8.1 Ford, Alexander C.; Mahadeva, Sanjiv; Carbone, M. Florencia; Lacy, Brian E.; Talley, Nicholas J. (2020-11-21). "Functional dyspepsia". The Lancet. 396 (10263): 1689–1702. doi:10.1016/S0140-6736(20)30469-4. ISSN 0140-6736. PMID 33049222. S2CID 222254300. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Greenberger, Norton; Blumberg, R.S.; Burakoff, Robert (2016). Current diagnosis & treatment. Gastroenterology, hepatology, and endoscopy (3 ed.). New York. ISBN 978-1-259-25097-2. OCLC 925478002. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  10. ↑ 10.0 10.1 10.2 "Rome IV Criteria". Rome Foundation. Archived from the original on 2022-01-19. Retrieved 2022-01-19.
  11. ↑ Flier, SN; S, Rose (2006). "Is functional dyspepsia of particular concern in women? A review of gender differences in epidemiology, pathophysiologic mechanism, clinical presentation and management". Am J Gastroenterol. 101 (12 Suppl): S644–53. doi:10.1111/j.1572-0241.2006.01015.x. PMID 17177870. S2CID 27922893.
  12. ↑ Vakil, Nimish (2006). "Limited Value of Alarm Features in the Diagnosis of Upper Gastrointestinal Malignancy: Systematic Review and Meta-analysis". Gastroenterology. 131 (2): 390–401. doi:10.1053/j.gastro.2006.04.029. PMID 16890592. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  13. ↑ 13.0 13.1 13.2 Barberio, Brigida; Mahadeva, Sanjiv; Black, Christopher J.; Savarino, Edoardo V.; Ford, Alexander C. (2020-07-28). "Systematic review with meta-analysis: global prevalence of uninvestigated dyspepsia according to the Rome criteria". Alimentary Pharmacology & Therapeutics. 52 (5): 762–773. doi:10.1111/apt.16006. ISSN 0269-2813. PMID 32852839. S2CID 221344221. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  14. ↑ 14.0 14.1 14.2 Sayuk, Gregory S.; Gyawali, C. Prakash (2020-09-01). "Functional Dyspepsia: Diagnostic and Therapeutic Approaches". Drugs. 80 (13): 1319–1336. doi:10.1007/s40265-020-01362-4. ISSN 1179-1950. PMID 32691294. S2CID 220656815. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  15. ↑ Holtmann, Gerald; Shah, Ayesha; Morrison, Mark (2017). "Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview". Digestive Diseases. 35 (S1): 5–13. doi:10.1159/000485409. ISSN 0257-2753. PMID 29421808. S2CID 3556796. Archived from the original on 2022-03-07. Retrieved 2022-03-28.
  16. ↑ Eusebi, Leonardo H.; Ratnakumaran, Raguprakash; Yuan, Yuhong; Solaymani-Dodaran, Masoud; Bazzoli, Franco; Ford, Alexander C. (March 2018). "Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis". Gut. 67 (3): 430–440. doi:10.1136/gutjnl-2016-313589. ISSN 1468-3288. PMID 28232473. S2CID 3496003. Archived from the original on 2022-04-08. Retrieved 2022-03-28.
  17. ↑ Fashner, Julia; Gitu, Alfred C. (2015-02-15). "Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection". American Family Physician. 91 (4): 236–242. ISSN 1532-0650. PMID 25955624. Archived from the original on 2022-04-21. Retrieved 2022-03-28.
  18. ↑ Ford, Alexander C.; Tsipotis, Evangelos; Yuan, Yuhong; Leontiadis, Grigorios I.; Moayyedi, Paul (2022-01-12). "Efficacy of Helicobacter pylori eradication therapy for functional dyspepsia: updated systematic review and meta-analysis". Gut: gutjnl–2021–326583. doi:10.1136/gutjnl-2021-326583. ISSN 1468-3288. PMID 35022266. S2CID 245922275. Archived from the original on 2022-01-28. Retrieved 2022-03-28.
  19. ↑ Talley NJ, Ford AC (Nov 5, 2015). "Functional Dyspepsia" (PDF). N Engl J Med (Review). 373 (19): 1853–63. doi:10.1056/NEJMra1501505. PMID 26535514. Archived (PDF) from the original on March 6, 2022. Retrieved March 28, 2022.
  20. ↑ 20.0 20.1 Jung HK, Talley NJ (2018). "Role of the Duodenum in the Pathogenesis of Functional Dyspepsia: A Paradigm Shift". J Neurogastroenterol Motil (Review). 24 (3): 345–354. doi:10.5056/jnm18060. PMC 6034675. PMID 29791992.
  21. ↑ 21.0 21.1 Stanghellini, Vincenzo; Chan, Francis K. L.; Hasler, William L.; Malagelada, Juan R.; Suzuki, Hidekazu; Tack, Jan; Talley, Nicholas J. (May 2016). "Gastroduodenal Disorders". Gastroenterology. 150 (6): 1380–1392. doi:10.1053/j.gastro.2016.02.011. ISSN 1528-0012. PMID 27147122. Archived from the original on 2022-03-16. Retrieved 2022-03-28.
  22. ↑ 22.0 22.1 Mounsey, Anne; Barzin, Amir; Rietz, Ashley (2020-01-15). "Functional Dyspepsia: Evaluation and Management". American Family Physician. 101 (2): 84–88. ISSN 1532-0650. PMID 31939638. Archived from the original on 2022-01-20. Retrieved 2022-03-28.
  23. ↑ Ford AC, Moayyedi P (2013). "Dysepsia". BMJ. 347: f5059. doi:10.1136/bmj.f5059. PMID 23990632. S2CID 220190440. Archived from the original on 2014-12-21. Retrieved 2022-03-28.
  24. ↑ 24.0 24.1 Duncanson, K. R.; Talley, N. J.; Walker, M. M.; Burrows, T. L. (June 2018). "Food and functional dyspepsia: a systematic review". Journal of Human Nutrition and Dietetics. 31 (3): 390–407. doi:10.1111/jhn.12506. ISSN 1365-277X. PMID 28913843. S2CID 22800900. Archived from the original on 2022-04-09. Retrieved 2022-03-28.
  25. ↑ Duncanson KR, Talley NJ, Walker MM, Burrows TL (2017). "Food and functional dyspepsia: a systematic review". J Hum Nutr Diet (Systematic Review). 31 (3): 390–407. doi:10.1111/jhn.12506. PMID 28913843. S2CID 22800900.
  26. ↑ Futagami S, Itoh T, Sakamoto C (2015). "Systematic review with meta-analysis: post-infectious functional dyspepsia". Aliment. Pharmacol. Ther. 41 (2): 177–88. doi:10.1111/apt.13006. PMID 25348873.
  27. ↑ Tan, V. P. Y.; Liu, K. S. H.; Lam, F. Y. F.; Hung, I. F. N.; Yuen, M. F.; Leung, W. K. (2017-01-23). "Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia". Alimentary Pharmacology & Therapeutics. 45 (6): 767–776. doi:10.1111/apt.13945. ISSN 0269-2813. PMID 28112426. S2CID 207052951. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  28. ↑ Enck, Paul; Azpiroz, Fernando; Boeckxstaens, Guy; Elsenbruch, Sigrid; Feinle-Bisset, Christine; Holtmann, Gerald; Lackner, Jeffrey M.; Ronkainen, Jukka; Schemann, Michael; Stengel, Andreas; Tack, Jan (2017-11-03). "Functional dyspepsia". Nature Reviews. Disease Primers. 3: 17081. doi:10.1038/nrdp.2017.81. ISSN 2056-676X. PMID 29099093. S2CID 4929427. Archived from the original on 2022-01-25. Retrieved 2022-03-28.
  29. ↑ Milivojevic, Vladimir; Rankovic, Ivan; Krstic, Miodrag N.; Milosavljevic, Tomica (2021-06-14). "Dyspepsia-challenge in primary care gastroenterology". Digestive Diseases. S. Karger AG. doi:10.1159/000517668. ISSN 0257-2753. PMID 34126614.
  30. ↑ 30.0 30.1 Ford, Alexander C.; Moayyedi, Paul; Black, Christopher J.; Yuan, Yuhong; Veettil, Sajesh K.; Mahadeva, Sanjiv; Kengkla, Kirati; Chaiyakunapruk, Nathorn; Lee, Yeong Yeh (2020-09-16). "Systematic review and network meta-analysis: efficacy of drugs for functional dyspepsia". Alimentary Pharmacology & Therapeutics. 53 (1): 8–21. doi:10.1111/apt.16072. ISSN 0269-2813. PMID 32936964. S2CID 221768794. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  31. ↑ 31.0 31.1 31.2 31.3 Duboc, Henri; Latrache, Sofya; Nebunu, Nicoleta; Coffin, Benoit (2020). "The Role of Diet in Functional Dyspepsia Management". Frontiers in Psychiatry. 11: 23. doi:10.3389/fpsyt.2020.00023. ISSN 1664-0640. PMC 7012988. PMID 32116840.
  32. ↑ 32.0 32.1 Pinto-Sanchez, Maria Ines; Yuan, Yuhong; Hassan, Ahmed; Bercik, Premysl; Moayyedi, Paul (2017-11-21). "Proton pump inhibitors for functional dyspepsia". The Cochrane Database of Systematic Reviews. 11: CD011194. doi:10.1002/14651858.CD011194.pub3. ISSN 1469-493X. PMC 6485982. PMID 29161458.
  33. ↑ Huang, Xinyi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Miwa, Hiroto (November 2021). "Meta-Analysis: Placebo Response and Its Determinants in Functional Dyspepsia". American Journal of Gastroenterology. 116 (11): 2184–2196. doi:10.14309/ajg.0000000000001397. ISSN 0002-9270. PMID 34404084. S2CID 237199057. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  34. ↑ Pittayanon, Rapat; Yuan, Yuhong; Bollegala, Natasha P; Khanna, Reena; Leontiadis, Grigorios I; Moayyedi, Paul (2018-10-18). Cochrane Upper GI and Pancreatic Diseases Group (ed.). "Prokinetics for functional dyspepsia". Cochrane Database of Systematic Reviews. 2018 (10): CD009431. doi:10.1002/14651858.CD009431.pub3. PMC 6516965. PMID 30335201.
  35. ↑ "Proton Pump Inhibitors: Use in Adults" (PDF). Centers for Medicare & Medicaid Services. 2015. Archived (PDF) from the original on 2022-01-27. Retrieved 2022-01-27.
  36. ↑ Heiran, Alireza; Bagheri Lankarani, Kamran; Bradley, Ryan; Simab, Alireza; Pasalar, Mehdi (2021-12-01). "Efficacy of herbal treatments for functional dyspepsia: A systematic review and meta-analysis of randomized clinical trials". Phytotherapy Research. doi:10.1002/ptr.7333. ISSN 1099-1573. PMID 34851546. S2CID 244774488. Archived from the original on 2022-01-27. Retrieved 2022-03-28.
  37. ↑ Kanfer, Isadore; Patnala, Srinivas (2021-01-01), Henkel, Ralf; Agarwal, Ashok (eds.), "Chapter 7 - Regulations for the use of herbal remedies", Herbal Medicine in Andrology, Academic Press, pp. 189–206, doi:10.1016/b978-0-12-815565-3.00007-2, ISBN 978-0-12-815565-3, S2CID 234186151, archived from the original on 2022-01-27, retrieved 2022-01-27
  38. ↑ Rodrigues, David M; Motomura, Douglas I; Tripp, Dean A; Beyak, Michael J (2021-06-16). "Are psychological interventions effective in treating functional dyspepsia? A systematic review and meta‐analysis". Journal of Gastroenterology and Hepatology. 36 (8): 2047–2057. doi:10.1111/jgh.15566. ISSN 0815-9319. PMID 34105186. S2CID 235379735. Archived from the original on 2022-05-07. Retrieved 2022-03-28.
  39. ↑ Esterita, Tasia; Dewi, Sheilla; Suryatenggara, Felicia Grizelda; Glenardi, Glenardi (2021-06-18). "Association of Functional Dyspepsia with Depression and Anxiety: A Systematic Review". Journal of Gastrointestinal and Liver Diseases: JGLD. 30 (2): 259–266. doi:10.15403/jgld-3325. ISSN 1842-1121. PMID 33951117. S2CID 233868221. Archived from the original on 2022-01-27. Retrieved 2022-03-28.
  40. ↑ Esterita, Tasia; Dewi, Sheilla; Suryatenggara, Felicia Grizelda; Glenardi, Glenardi (2021-06-18). "Association of Functional Dyspepsia with Depression and Anxiety: A Systematic Review". Journal of Gastrointestinal and Liver Diseases. 30 (2): 259–266. doi:10.15403/jgld-3325. ISSN 1842-1121. PMID 33951117. S2CID 233868221. Archived from the original on 2022-01-27. Retrieved 2022-03-28.
  41. ↑ Tsukanov, V. V.; Vasyutin, A. V.; Tonkikh, Ju. L. (2020-10-22). "Modern aspects of the pathogenesis and treatment of dyspepsia". Meditsinskiy Sovet = Medical Council (15): 40–46. doi:10.21518/2079-701x-2020-15-40-46. ISSN 2658-5790. S2CID 226340276.

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