Diseases

Indigestion is diagnosed primarily on the basis of typical symptoms and the exclusion of non-functional gastrointestinal diseases (including acid-related diseases), non-gastrointestinal diseases, and psychiatric illness. There are tests for identifying abnormal gastrointestinal function directly, but they are limited in their ability to do so.

Indigestion is a chronic disease that usually lasts years, if not a lifetime. It does, however, display periodicity, which means that the symptoms may be more frequent or severe for days, weeks, or months and then less frequent or severe for days, weeks, or months. The reasons for these fluctuations are unknown. Because of the fluctuations, it is important to judge the effects of treatment over many weeks or months to be certain that any improvement is due to treatment and not simply to a natural fluctuation in the frequency or severity of the disease.

It is appropriate to discuss belching in detail since it is a commonly misunderstood symptom associated with indigestion.

• The ability to belch is almost universal.
• Belching, also known as burping or eructating, is the act of expelling gas from the stomach out through the mouth.
• The usual cause of belching is a distended (inflated) stomach that is caused by swallowed air or gas.
• The distention of the stomach causes abdominal discomfort, and the belching expels the air and relieves the discomfort.
• The common reasons for swallowing large amounts of air (aerophagia) or gas are
  • gulping food or drink too rapidly,
  • anxiety, and
  • carbonated beverages.
• People often are unaware that they are swallowing air.
• "Burping" infants during bottle or breastfeeding is important in order to expel air in the stomach that has been swallowed with the formula or milk.

Excessive air in the stomach is not the only cause of belching.

• For some people, belching becomes a habit and does not reflect the amount of air in their stomachs.
• For others, belching is a response to any type of abdominal discomfort and not just to discomfort due to increased gas.

The complications of functional diseases of the gastrointestinal tract are relatively limited. Since symptoms are most often provoked by eating, patients who alter their diets and reduce their intake of calories may lose weight. However, loss of weight is unusual in functional diseases. In fact, loss of weight should suggest the presence of non-functional diseases. Symptoms that awaken patients from sleep also are more likely to be due to non-functional than functional disease.Most commonly, functional diseases interfere with patients' comfort and daily activities. Individuals who develop nausea or pain after eating may skip breakfast or lunch because of the symptoms they experience. Patients also commonly associate symptoms with specific foods (for example, milk, fat, vegetables). Whether or not the associations are real, these patients will restrict their diets accordingly. Milk is the most common food that is eliminated, often unnecessarily, and this can lead to inadequate intake of calcium and osteoporosis. The interference with daily activities also can lead to problems with interpersonal relationships, especially with spouses. Most patients with functional disease live with their symptoms and infrequently visit physicians for diagnosis and treatment.

We usually think of symptoms of indigestion as originating from the upper gastrointestinal tract, primarily the stomach and first part of the small intestine. These symptoms include:

• upper abdominal pain or discomfort (above or around the navel),
• belching,
• nausea (with or without vomiting),
• abdominal bloating (the sensation of abdominal fullness without visible distention),
• early satiety (the sensation of fullness after a very small amount of food),
• abdominal distention (visible swelling as opposed to bloating), and
• lower chest pain.

The symptoms most often are provoked by eating, which is a time when many different gastrointestinal functions are called upon to work in concert. This tendency to occur after meals is what gave rise to the erroneous notion that indigestion might be caused by an abnormality in the digestion of food.

The initial approach to dyspepsia, whether it be treatment or testing, depends on the patient's age, symptoms and the duration of the symptoms. If the patient is younger than 50 years of age and serious disease, particularly cancer, is not likely, testing is less important. If the symptoms are typical for dyspepsia and have been present for many years without change, then there is less need for testing, or at least extensive testing, to exclude other gastrointestinal and non-gastrointestinal diseases.On the other hand, if the symptoms are of recent onset (weeks or months), progressively worsening, severe, or associated with "warning" signs, then early, more extensive testing is appropriate. Warning signs include loss of weight, nighttime awakening, blood in the stool or the material that is vomited (vomitus), and signs of inflammation, such as fever or abdominal tenderness. Testing also is appropriate if, in addition to symptoms of dyspepsia, there are other prominent symptoms that are not commonly associated with dyspepsia.If there are symptoms that suggest conditions other than dyspepsia, tests that are specific for these diseases should be done first. The reason is that if these other tests disclose other diseases, it may not be necessary to do additional testing. Examples of such symptoms and possible testing include:

• Vomiting: upper gastrointestinal endoscopy to diagnose inflammatory or obstructing diseases; gastric emptying studies and/or electrogastrography to diagnose impaired emptying of the stomach.
• Abdominal distention with or without increased flatulence: upper gastrointestinal and small intestinal x-rays to diagnose obstructing diseases; hydrogen breath testing to diagnose bacterial overgrowth of the small intestine.

For a patient with typical symptoms of dyspepsia who requires testing to exclude other diseases, a standard screening panel of blood tests would reasonably be included. These tests might reveal clues to non-gastrointestinal diseases. Sensitive stool testing (antigen/antibody) for Giardia lamblia would be reasonable because this parasitic infection is common and can be acute or chronic. Some physicians do blood testing for celiac disease (sprue), but the value of doing this is unclear. Moreover, if an EGD is planned, biopsies of the duodenum usually will make the diagnosis of celiac disease. A plain X-ray of the abdomen might be done during an episode of abdominal pain (to look for intestinal blockage or obstruction). Testing for lactose intolerance or a trial of a strict lactose-free diet should be considered. The physician's clinical judgment should determine the extent to which initial testing is appropriate.Once testing has been done to an extent that is appropriate for the clinical situation, it is reasonable to first try a therapeutic trial of stomach acid suppression to see if symptoms improve. Such a trial probably should involve a PPI (proton pump inhibitor) for 8 to 12 weeks. If there is no clear response of symptoms, the options then are to discontinue the PPI or confirm its effectiveness in suppressing acid with 24 hour acid testing. If there is a clear and substantial decrease in symptoms with the PPI, then decisions need to be made about continuing acid suppression and which drugs to use.Another therapeutic approach is to test for Helicobacter pylori infection of the stomach (with blood, breath or stool tests) and to treat patients with infection to eradicate the infection. It may be necessary to retest patients after treatment to prove that treatment has effectively eradicated the infection, particularly if dyspeptic symptoms persist after treatment.If treatment with a PPI has satisfactorily suppressed acid according to acid testing (or acid suppression has not been measured) and yet the symptoms have not improved, it is reasonable to conduct further testing as described above. Esophago-gastro-duodenoscopy, or EGD, (and, possibly, colonoscopy) would be the next consideration, probably with multiple biopsies of the stomach and duodenum (and colon if colonoscopy is done). Finally, small intestinal x-rays and an ultrasound examination of the gallbladder might be done. An abdominal ultrasound examination, CT scan, or MRI scan can exclude non-gastrointestinal diseases. Once appropriate testing has been completed, empiric trials of other drugs (for example, smooth muscle relaxants, psychotropic drugs, and promotility drugs) can be done. (An empiric trial of a drug is a trial that is not based on an understanding of the exact cause of the symptoms)If all of the appropriate testing reveals no disease that could be causing the symptoms and the dyspeptic symptoms have not responded to empiric treatments, other, more specialized tests should be considered. These tests include hydrogen breath testing to diagnose bacterial overgrowth of the small intestine, gastric emptying studies, EGG, small intestinal transit studies, antro-duodenal motility and barostatic studies, and possibly capsule endoscopy. These specialized studies probably should be done at centers that have experience and expertise in diagnosing and treating functional diseases.

Non-gastrointestinal causes of indigestionIt's not surprising that many gastrointestinal (GI) diseases have been associated with indigestion. However, many non-GI diseases also have been associated with indigestion. Examples of non-GI causes of indigestion include

• diabetes,
• thyroid disease,
• hyperparathyroidism (overactive parathyroid glands), and
• severe kidney disease.

It is not clear, however, how these non-GI diseases might cause indigestion.Another important cause of indigestion is drugs. Many drugs are frequently associated with indigestion, for example, nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen), antibiotics, and estrogens). In fact, most drugs are reported to cause indigestion in at least some people.Gastrointestinal causes of indigestionAs discussed previously, most indigestion (not due to non-GI diseases or drugs) is believed to be due to abnormal function of the muscles of the organs of the gastrointestinal tract or the nerves controlling the organs. The nervous control of the GI tract, however, is complex. A system of nerves runs the entire length of the gastrointestinal tract from the esophagus to the anus in the muscular walls of the organs. These nerves communicate with other nerves that travel to and from the spinal cord. Nerves within the spinal cord, in turn, travel to and from the brain. (The GI tract is exceeded in the numbers of nerves it contains only by the spinal cord and brain.) Thus, abnormal function of the nervous system in indigestion might occur in a gastrointestinal muscular organ, the spinal cord, or the brain.The nervous system controlling the gastrointestinal organs, as with most other organs, contains both sensory and motor nerves. The sensory nerves continuously sense what is happening (activity) within the organ and relay this information to nerves in the organ's wall. From there, information can be relayed to the spinal cord and brain. The information is received and processed in the organ's wall, the spinal cord, or the brain. Then, based on this sensory input and the way the input is processed, commands (responses) are sent to the organ over the motor nerves. Two of the most common motor responses in the intestine are contraction or relaxation of the muscle of the organ and secretion of fluid and/or mucus into the organ.As already mentioned, abnormal function of the nerves of the gastrointestinal organs, at least theoretically, might occur in the organ, spinal cord, or brain. Moreover, the abnormalities might occur in the sensory nerves, the motor nerves, or at processing centers in the intestine, spinal cord, or brain.Some researchers argue that the cause of functional diseases is abnormalities in the function of sensory nerves. For example, normal activities, such as stretching of the small intestine by food, may give rise to sensory signals that are sent to the spinal cord and brain, where they are perceived as painful. Other researchers argue that the cause of functional diseases is abnormalities in the function of motor nerves. For example, abnormal commands through the motor nerves might produce painful spasm (contraction) of the muscles. Still others argue that abnormally functioning processing centers are responsible for functional diseases because they misinterpret normal sensations or send abnormal commands to the organ. In fact, some functional diseases may be due to sensory dysfunction, motor dysfunction, or both sensory and motor dysfunction. Others may be due to abnormalities within the processing centers.An important concept that is relevant to these several potential mechanisms (causes) of functional diseases is the concept of "visceral hypersensitivity". This concept states that diseases affecting the gastrointestinal organs (viscera) "sensitize" (alter the responsiveness of) the sensory nerves or the processing centers to sensations coming from the organ. According to this theory, a disease such as colitis (inflammation of the colon) can cause permanent changes in the sensitivity of the nerves or processing centers of the colon. As a result of this prior inflammation, normal stimuli are perceived (felt) as abnormal (for example, as being painful). Thus, a normal colonic contraction may be painful. It is not clear what prior diseases might lead to hypersensitivity in people, although infectious diseases (bacterial or viral) of the gastrointestinal tract are mentioned most often. Visceral hypersensitivity has been demonstrated clearly in animals and people. Its role in the common functional diseases, however, is unclear.Another potential cause of indigestion is bacterial overgrowth of the small intestine (small intestinal bacterial overgrowth or SIBO), although the frequency with which this condition causes indigestion has not been determined, and there is little research in the area. The relationship between overgrowth and indigestion needs to be pursued, however, since many of the symptoms of indigestion are also symptoms of bacterial overgrowth. Overgrowth can be diagnosed by hydrogen breath testing and is treated primarily with antibiotics.Other diseases and conditions can aggravate functional diseases, including indigestion. Anxiety and/or depression are probably the most commonly-recognized exacerbating factors for patients with functional diseases. Another aggravating factor is the menstrual cycle. During their periods, women often note that their functional symptoms are worse. This corresponds to the time during which the female hormones, estrogen and progesterone, are at their highest levels. Furthermore, it has been observed that treating women who have indigestion with leuprolide (Lupron), an injectable drug that shuts off the body's production of estrogen and progesterone, is effective at reducing symptoms of indigestion in premenopausal women. These observations support a role for hormones in the intensification of functional symptoms.

Indigestion is one of the most common ailments of the bowel (intestines), affecting an estimated 20% of persons in the United States. Perhaps only 10% of those affected actually seek medical attention for their indigestion. Indigestion is not a particularly good term for the ailment since it implies that there is "dyspepsia" or abnormal digestion of food, and this most probably is not the case. In fact, another common name for dyspepsia is indigestion, which, for the same reason, is no better than the term dyspepsia! Doctors frequently refer to the condition as non-ulcer dyspepsia to distinguish it from the more common acid or ulcer-related symptoms.Dyspepsia (indigestion) is best described as a functional disease. (Sometimes, it is called functional dyspepsia.) The concept of functional disease is particularly useful when discussing diseases of the gastrointestinal tract. The concept applies to the muscular organs of the gastrointestinal tract, the esophagus, stomach, small intestine, gallbladder, and colon that are controlled y nerves. What is meant by the term, functional, is that either the muscles of the organs or the nerves that control the organs are not working normally, and, as a result, the organs do not function normally, and the dysfunction causes the symptoms. The nerves that control the organs include not only the nerves that lie within the muscles of the organs but also the nerves of the spinal cord and brain.Some gastrointestinal diseases can be seen and diagnosed with the naked eye, such as ulcers of the stomach and can be seen at surgery, on X-rays, and by endoscopy. Other diseases cannot be seen with the naked eye but can be seen and diagnosed under the microscope. For example, gastritis (inflammation of the stomach) can be diagnosed by microscopic examination of biopsies of the stomach. In contrast, gastrointestinal functional diseases cannot be seen with the naked eye or the microscope. Accordingly, and by default, functional gastrointestinal diseases are those that involve abnormal function of gastrointestinal organs in which the abnormalities cannot be seen in the organs with either the naked eye or the microscope.In some instances, the abnormal function can be demonstrated by tests (for example, gastric emptying studies or antro-duodenal motility studies). However, the tests often are complex, are not widely available, and do not reliably detect the functional abnormalities.Occasionally, diseases that are thought to be functional are ultimately found to be associated with abnormalities that can be seen by the naked eye or under the microscope. Then, the disease moves out of the functional category. An example of this would be Helicobacter pylori (H. pylori) infection of the stomach. Some patients with mild upper gastrointestinal symptoms who were thought to have abnormal function of the stomach or intestines have been found to have stomachs infected with H. pylori. This infection can be diagnosed under the microscope by identifying the bacterium in biopsies from the stomach. When patients are treated with antibiotics, the H. pylori and symptoms disappear. Thus, recognition of infections with Helicobacter pylori has removed some patients' symptoms from the functional disease category.The distinction between functional disease and non-functional disease may, in fact, be blurry. Thus, even functional diseases probably have associated biochemical or molecular abnormalities that ultimately will be able to be measured. For example, functional diseases of the stomach and intestines may be shown ultimately to be associated with reduced or increased levels of normal chemicals within the gastrointestinal organs, the spinal cord, or the brain. Should a disease that is demonstrated to be due to a reduced or increased chemical still be considered a functional disease? In this theoretical situation, we can't see the abnormality with the naked eye or the microscope, but we can measure it. If we can measure an associated or causative abnormality, should the disease no longer be considered functional, even though the disease (symptoms) are being caused by abnormal function? The answer is unclear.Despite the shortcomings of the term, functional, the concept of a functional abnormality is useful for approaching many of the symptoms originating from the muscular organs of the gastrointestinal tract. To repeat, this concept applies to those symptoms for which there are no associated abnormalities that can be seen with the naked eye or the microscope.While dyspepsia is a major functional disease(s), it is important to mention several other functional diseases. A second major functional disease is the irritable bowel syndrome, or IBS. The symptoms of IBS are thought to originate primarily from the small intestine and/or colon. The symptoms of IBS include abdominal pain that is accompanied by alterations in bowel movements (defecation), primarily constipation or diarrhea. In fact, indigestion and IBS may be overlapping diseases since up to half of patients with IBS also have symptoms of indigestion. A third distinct functional disorder is non-cardiac chest pain. This pain may mimic heart pain (angina), but it is unassociated with heart disease. In fact, non-cardiac chest pain is thought to often result from a functional abnormality of the esophagus.Functional disorders of the gastrointestinal tract often are categorized by the organ of involvement. Thus, there are functional disorders of the esophagus, stomach, small intestine, colon, and gallbladder. The amount of research that has been done with functional disorders is greatest in the esophagus and stomach (for example, non-cardiac chest pain, indigestion), perhaps because these organs are easiest to reach and study. Research into functional disorders affecting the small intestine and colon (IBS) is more difficult to conduct, and there is less agreement among the research studies. This probably is a reflection of the complexity of the activities of the small intestine and colon and the difficulty in studying these activities. Functional diseases of the gallbladder (referred to as biliary dyskinesia), like those of the small intestine and colon, also are more difficult to study, and at present they are less well-defined. Each of the functional diseases is associated with its own set of characteristic symptoms.Picture of the organs and glands in the abdomen

Studies of natural and home remedies for indigestion are few. Most recommendations for natural and home remedies have little evidence to support their use. Several potential remedies, however, deserve mention including:

• Acid-suppressing remedies: The most common cause of dyspepsia is probably gastrointestinal reflux disease (acid reflux or GERD). That may be why remedies such as baking soda, which neutralizes stomach acid, have been recommended. Even if baking soda works, it is more effective (and probably safer) to use antacids in liquid or pill form for this purpose.
• Ginger: Ginger has been demonstrated to relieve nausea. One small study showed it to be ineffective in relieving dyspepsia, but ginger is harmless and worth a try if nausea is a component of the dyspepsia.
• Peppermint: Peppermint has been demonstrated to have effects on the function of the gastrointestinal tract; it is among the most potent inhibitors of intestinal muscles. It is effective in another functional disease, irritable bowel syndrome, but there is minimal evidence that it is effective in dyspepsia. Nevertheless, like ginger, it is harmless and worth a try.
• Meals: Eating smaller, more frequent meals.
• Lifestyle changes: Stay away from specific foods and drinks, smoking, and alcohol if they provoke symptoms.

Exclusion of non-functional gastrointestinal diseaseAs always, a detailed history from the patient and a physical examination frequently will suggest the cause of dyspepsia. Routine screening blood tests often are performed looking for clues to unsuspected diseases. Examinations of stool also are a part of the evaluation since they may reveal infection, signs of inflammation, or blood and direct further diagnostic testing. Sensitive stool testing (antigen/antibody) for Giardia lamblia would be reasonable because this parasitic infection is common and can be acute or chronic. Some physicians do blood testing for celiac disease (sprue), but the value of doing this is unclear. (Moreover, if an EGD is planned, biopsies of the duodenum usually will make the diagnosis of celiac disease.) If bacterial overgrowth of the small intestine is being considered, breath hydrogen testing can be considered.There are many tests to exclude non-functional gastrointestinal diseases. The primary issue, however, is to decide which tests are reasonable to perform. Since each case is individual, different tests may be reasonable for different patients. Nevertheless, certain basic tests are often performed to exclude non-functional gastrointestinal disease. These tests identify anatomic (structural) and histological (microscopic) diseases of the esophagus, stomach, and intestines.Both X-rays and endoscopies can identify anatomic diseases. Only endoscopies, however, can diagnose histological diseases because biopsies (samples of tissue) can be taken during the procedure. The X-ray tests include:

• The esophagram and video-fluoroscopic swallowing study for examining the esophagus
• The upper gastrointestinal series for examining the stomach and duodenum
• The small bowel series for examining the small intestine
• The barium enema for examining the colon and terminal ileum.
• The computerized tomography (CT) scan for examining the small intestine

The endoscopic tests include:

• Upper gastrointestinal endoscopy (esophago-gastro-duodenoscopy or EGD) to examine the esophagus, stomach and duodenum
• Colonoscopy to examine the colon and terminal ileum
• Endoscopy also is available to examine the small intestine, but this type of endoscopy is complex, not widely available, and of unproven value in indigestion.

For examination of the small intestine, there is also a capsule containing a tiny camera and transmitter that can be swallowed (capsule endoscopy). As the capsule travels through the intestines, it transmits pictures of the inside of the intestines to an external recorder for later review. The capsule is not widely available and its value, particularly in indigestion, has not yet been proven.Newer endoscopes, similar to those used for EGD and colonoscopy are available that allow the entire small intestine to be examined. Unlike the capsule, however, the endoscope has channels in it that allow instruments to be passed into the intestine to collect samples of tissue (biopsies) and to treat abnormal findings such as polyps.X-rays are easier to perform and less costly than endoscopies. The skills necessary to perform gastrointestinal X-rays, however, are becoming rare among radiologists because they are doing them less often. Therefore, the quality of the X-rays often is not as high as it used to be, and, as a result, CT scans of the small intestine are replacing small intestinal X-rays. As noted previously, endoscopies have an advantage over X-rays since at the time of endoscopies, biopsies can be taken to diagnose or exclude histological diseases, something that X-rays cannot do.Exclusion of acid-related gastrointestinal diseasesBecause they are so common, the most important non-functional gastrointestinal diseases to exclude are acid-related diseases that cause inflammation and ulceration of the esophagus, stomach, and duodenum. Infection of the stomach with Helicobacter pylori, an infection that is closely associated with some acid-related diseases, is included in this group. It is not clear, however, how often Helicobacter pylori causes indigestion. Moreover, the only way of excluding this bacterium as a cause of indigestion in a particular patient is by eliminating the infection (if it is present) with appropriate antibiotics. If indigestion is substantially improved by eradication, it is likely that the bacterium was responsible. Helicobacter pylori infection also can be diagnosed (or excluded) by blood tests, biopsy of the stomach, urea breath test, or a stool test.Endoscopy is a good way of diagnosing or excluding acid-related inflammation. If no signs of inflammation are present, acid-related diseases are unlikely. Nevertheless, many patients without signs of inflammation respond to potent and prolonged suppression of acid, suggesting that acid is causing their indigestion. Therefore, many physicians will use potent suppression of acid in indigestion as a means to both treat and diagnose. Thus, if indigestion improves substantially (more than 50% to 75%) with suppression of acid, they consider it likely that acid is responsible for the indigestion. For this purpose, it is important to use potent acid suppression with proton pump inhibitors (PPIs), such as:

• omeprazole (Prilosec, Zegerid)
• lansoprazole (Prevacid)
• rabeprazole (Aciphex)
• pantoprazole (Protonix)
• esomeprazole (Nexium)
• dexlansoprazole (Dexilant)

Treatment often is given at higher than recommended doses for 12 weeks or more before a decision is made about the effect of treatment on the symptoms. (A short course for just a few days or weeks is not enough.) If the symptoms of indigestion do not improve, it even may be reasonable to check the amount of acid produced by the stomach (and also the reflux of acid into the esophagus) by 24 hour pH monitoring to be certain that the acid-suppressing drugs are effectively suppressing acid. (Up to 10% of patients are resistant to the effects of even the PPIs.)Exclusion of non-gastrointestinal diseasePatients with indigestion often undergo abdominal ultrasonography (US), computerized tomography (CT or CAT scans), or magnetic resonance imaging (MRI). These tests are used primarily to diagnose non-intestinal diseases. (Although the tests also are capable of diagnosing intestinal diseases, their value for this purpose is limited. X-ray and endoscopy are better.) It is important to realize that US, CT, and MRI are powerful tests and may uncover abnormalities that are unrelated to indigestion. The most common example of this is the finding of gallstones that, in fact, are causing no symptoms. (At least up to 50% of gallstones cause no symptoms.) This can cause a problem if the gallstones are assumed to be causing the indigestion. Surgical removal of the gallbladder with its gallstones (cholecystectomy) is unlikely to relieve the indigestion. (Cholecystectomy would be expected to relieve only the characteristic symptoms that gallstones can cause.) Additional tests to exclude non-gastrointestinal diseases may be appropriate in certain specific situations, although certainly not in most patients.Exclusion of psychiatric diseaseThe possibility of psychiatric (psychological or psychosomatic) illness often arises in patients with indigestion because the symptoms are subjective and no objective abnormalities can be identified. Psychiatric illness may complicate indigestion, but it is unclear if psychiatric illness can cause indigestion. If there is a possibility of psychiatric illness, a psychiatric evaluation is appropriate, and psychiatric treatment may improve (though probably not cure) the symptoms.

The future of dyspepsia will depend on our increasing knowledge of the processes (mechanisms) that cause dyspepsia. Acquiring this knowledge, in turn, depends on research funding. Because of the difficulties in conducting research in dyspepsia, this knowledge will not come quickly. Until we have an understanding of the mechanisms of dyspepsia, newer treatments will be based on our developing a better understanding of the normal control of gastrointestinal function, which is proceeding more rapidly. Specifically, there is intense interest in intestinal neurotransmitters, which are chemicals that the nerves of the intestine use to communicate with each other. The interactions of these neurotransmitters are responsible for adjusting (modulating) the functions of the intestines, such as contraction of muscles and secretion of fluid and mucus.5-hydroxytriptamine (5-HT or serotonin) is a neurotransmitter that stimulates several different receptors on nerves in the intestine. Examples of experimental drugs for intestinal neurotransmission are sumatriptan (Imitrex) and buspirone (Buspar). These drugs are believed to reduce the responsiveness (sensitivity) of the sensory nerves to what's happening in the intestine by attaching to a particular 5-HT receptor, the 5-HT1 receptor. The 5-HT1 receptor drugs, however, have received only minimal study so far and their role in the treatment of dyspepsia, if any, is unclear.Promotility drugs similar to cisapride, as previously discussed, are being pursued actively.Another area of active research is relaxation of the muscles of the stomach for the treatment of dyspepsia. Normally when food enters the stomach, the stomach relaxes to accommodate the food and the secretions it stimulates. Many patients with dyspepsia have been found to have reduced relaxation of the stomach when food enters, and it is possible that this results in discomfort. Drugs that specifically relax the muscles of the stomach are being developed, but more clinical trials showing their benefit are needed.

The treatment of indigestion is a difficult and unsatisfying topic because so few drugs have been studied and have been shown to be effective. Moreover, the drugs that have been shown to be effective have not been shown to be very effective. This difficult situation exists for many reasons including:

• Life-threatening illnesses (for example, cancer, heart disease, and high blood pressure) are the illnesses that capture the public's interest and, more importantly, research funding. Indigestion is not a life-threatening illness and has received little research funding. Because of the lack of research, an understanding of the physiologic processes (mechanisms) that are responsible for indigestion has been slow to develop. Effective drugs cannot be developed until there is an understanding of these mechanisms.
• Research in indigestion is difficult. Indigestion is defined by subjective symptoms (such as pain) rather than objective signs (for example, the presence of an ulcer). Subjective symptoms are more unreliable than objective signs in identifying homogenous groups of patients. As a result, groups of patients with indigestion who are undergoing treatment are likely to contain some patients who do not have indigestion, which may dilute (negatively affect) the results of the treatment. Moreover, the results of treatment must be evaluated on the basis of subjective responses (such as improvement of pain). In addition to being more unreliable, subjective responses are more difficult to measure than objective responses (for example, healing of an ulcer).
• Different subtypes of indigestion (for example, abdominal pain and abdominal bloating) are likely to be caused by different physiologic processes (mechanisms). It also is possible, however, that the same subtype of indigestion may be caused by different mechanisms in different people. What's more, any drug is likely to affect only one mechanism. Therefore, it is unlikely that any one medication can be effective in all-even most-patients with indigestion, even patients with similar symptoms. This inconsistent effectiveness makes the testing of drugs particularly difficult. Indeed, it can easily result in drug trials that demonstrate no efficacy (usefulness) when, in fact, the drug is helping a subgroup of patients.
• Subjective symptoms are particularly prone to responding to placebos (inactive drugs). In fact, in most studies, 20% to 40% of patients with indigestion will improve if they receive placebo drugs. Now, all clinical trials of drugs for indigestion require a placebo-treated group for comparison with the drug-treated group. The large placebo response means that these clinical trials must utilize large numbers of patients to detect meaningful (significant) differences in improvement between the placebo and drug groups. Therefore, these trials are expensive to conduct.

The lack of understanding of the physiologic processes (mechanisms) that cause indigestion has meant that treatment usually cannot be directed at the mechanisms. Instead, treatment usually is directed at the symptoms. For example, nausea is treated with medications that suppress nausea but do not affect the cause of the nausea. On the other hand, the psychotropic drugs (antidepressants) and psychological treatments (such as cognitive behavioral therapy) treat hypothetical causes of indigestion (for example, abnormal function of sensory nerves and the psyche) rather than causes or even the symptoms. Treatment for indigestion often is similar to that for irritable bowel syndrome (IBS) even though the causes of IBS and indigestion are likely to be different.EducationIt is important to educate patients with indigestion about their illness, particularly by reassuring them that the illness is not a serious threat to their physical health (though it may be to their emotional health). Patients need to understand the potential causes for the symptoms. Most importantly, they need to understand the medical approach to the problem and the reasons for each test or treatment. Education prepares patients for a potentially prolonged course of diagnosis and trials of treatment. Education also may prevent patients from falling prey to the charlatans who offer unproven and possibly dangerous treatments for indigestion. Many symptoms are tolerable if patients' anxieties about the seriousness of their symptoms can be relieved. It also helps patients deal with symptoms when they feel that everything that should be done to diagnose and treat, in fact, is being done. The truth is that psychologically healthy people can tolerate a good deal of discomfort and continue to lead happy and productive lives.

Since indigestion is very common, almost all doctors see and treat patients with indigestion, especially family practitioners, internists and even pediatricians. If these generalists are unable to provide adequate treatment, the patient usually is referred to a gastroenterologist, an internist or pediatrician with specialty training in gastrointestinal diseases.