Dyspepsia 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 dyspepsia. Dyspepsia 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.
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-esophagus, stomach, small intestine, gallbladder, and colon.
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. 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. Thus, ulcers can be seen at surgery, on x-rays, and 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) is diagnosed by microscopic examination of biopsies of the stomach. In contrast, gastrointestinal functional diseases cannot be seen with the naked eye or with 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. 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.
Occasionally, diseases that are thought to be functional are ultimately found to be associated with abnormalities that can be seen. 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. When patients are treated with antibiotics, the H. pylori and symptoms disappear. Thus, recognition of infections with Helicobacter pylori has removed some patients' systems 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? I think not. 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, the disease probably should no longer be considered functional.
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, dyspepsia and IBS may be overlapping diseases since up to half of patients with IBS also have symptoms of dyspepsia. 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 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, dyspepsia), 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.
We usually think of symptoms of dyspepsia as originating from the upper gastrointestinal tract, primarily the stomach and first part of the small intestine.
These symptoms include:
- upper abdominal pain (above the navel),
- nausea (with or without vomiting),
- abdominal bloating (the sensation of abdominal fullness without objective distention),
- early satiety (the sensation of fullness after a very small amount of food),
- possibly, abdominal distention (swelling as opposed to bloating).
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 notion that dyspepsia might be caused by an abnormality in the digestion of food.
It is appropriate to discuss belching in detail since it is a commonly misunderstood symptom associated with dyspepsia. 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. Moreover, if there is not excess air in the stomach, the act of belching actually may cause more air to be swallowed. "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.
Everyone knows that when they have mild abdominal discomfort, belching often relieves the problem. This is because excessive air in the stomach is often the cause of mild abdominal discomfort. As a result, people belch whenever mild abdominal discomfort is felt-whatever the cause.
If the problem causing the discomfort is not excessive air in the stomach, then belching does not provide relief. As mentioned previously, it even may make the situation worse by increasing air in the stomach. When belching does not ease the discomfort, the belching should be taken as a sign that something may be wrong within the abdomen and that the cause of the discomfort should be sought.
Belching by itself, however, does not help the physician determine what may be wrong because belching can occur in virtually any abdominal disease or condition that causes discomfort.
It's not surprising that many gastrointestinal diseases have been associated with dyspepsia. However, many non-gastrointestinal diseases also have been associated with dyspepsia. Examples of the latter include diabetes, thyroid disease, hyperparathyroidism (overactive parathyroid glands), and severe kidney disease. It is not clear, however, how these non-gastrointestinal diseases might cause dyspepsia.
A second important cause of dyspepsia is drugs. It turns out that many drugs are frequently associated with dyspepsia, for example, nonsteroidal anti-inflammatory drugs (NSAIDs such asibuprofen), antibiotics, and estrogens. In fact, most drugs are reported to cause dyspepsia in at least some patients.
As discussed previously, most dyspepsia (not due to non-gastrointestinal diseases or drugs) is believed to be due to abnormal function (dysfunction) of the muscles of the organs of the gastrointestinal tract or the nerves controlling the organs. The nervous control of the gastrointestinal 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. Thus, abnormal function of the nervous system in dyspepsia 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 dyspepsia is bacterial overgrowth of the small intestine (small intestinal bacterial overgrowth), although the frequency with which this condition causes dyspepsia has not been determined, and there is little research in the area. The relationship between overgrowth and dyspepsia needs to be persued, however, since many of the symptoms of dyspepsia 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 dyspepsia. 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 dyspepsia with leuprolide (Lupron), an injectable drug that shuts off the body's production of estrogen and progesterone, is effective at reducing symptoms of dyspepsia in premenopausal women. These observations support a role for hormones in the intensification of functional symptoms.
The treatment of dyspepsia is a difficult and unsatisfying topic because so few drugs have been studied and have shown to be effective. Moreover, the drugs that have been shown to be useful have not been substantially effective.
This difficult situation exists for many reasons, as follows:
- 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. Dyspepsia 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 dyspepsia has been slow to develop. Effective drugs cannot be developed until there is an understanding of these mechanisms.
- Research in dyspepsia is difficult. Dyspepsia 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 dyspepsia who are undergoing treatment are likely to contain some patients who do not have dyspepsia, 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 dyspepsia (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 dyspepsia may be caused by different mechanisms in different people. What's more, any drug is likely to affect only one mechanism. There fore, it is unlikely that any one medication can be effective in all-even most-patients with dyspepsia, 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 dyspepsia will improve if they receive inactive drugs. Now, all clinical trials of drugs for dyspepsia 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. There fore, these trials are expensive to conduct.
The lack of understanding of the physiologic processes (mechanisms) that cause dyspepsia 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 (anti depressants) and psychological treatments (such as cognitive behavioral therapy) treat hypothetical causes of dyspepsia (for example, abnormal function of sensory nerves and the psyche) rather than the symptoms. Treatment for dyspepsia often is similar to that for irritable bowel syndrome (IBS) even though the causes of IBS and dyspepsia are likely to be different.
It is important to educate patients with dyspepsia 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 mechanisms (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 dyspepsia. 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.
Dietary factors have not been well-studied in the treatment of dyspepsia. Nevertheless, patients often associate their symptoms with specific foods (such as salads and fats). Although specific foods might worsen the symptoms of dyspepsia, it is clear that they are not the cause of dyspepsia. The common placebo response in functional disorders such as dyspepsia also may explain the improvement of symptoms in some people with the elimination of specific foods.
Dietary fiber often is recommended for patients with IBS, but fiber has not been studied in the treatment of dyspepsia. Nevertheless, it probably is reasonable to treat patients with dyspepsia with fiber if they also have constipation.
Intolerance to lactose (the sugar in milk) often is blamed for dyspepsia. Since dyspepsia and lactose intolerance both are common, the two conditions may coexist. In this situation, restricting lactose will improve the symptoms of lactose intolerance, but will not affect the symptoms of dyspepsia.
Lactose intolerance is easily determined by testing the effects of lactose (hydrogen breath testing) or trying a strict lactose elimination diet. If lactose is determined to be responsible for some or all of the symptoms, elimination of lactose-containing foods is appropriate.
Unfortunately, many patients stop drinking milk or eating milk-containing foods without good evidence that it improves their symptoms. This often is detrimental to their intake of calcium which may contribute to osteoporosis.
One of the food substances most commonly associated with the symptoms of dyspepsia is fat. The scientific evidence that fat causes dyspepsia is weak. Most of the support is anecdotal (not based on carefully done, scientific studies). Nevertheless, fat is one of the most potent influences on gastrointestinal function. It tends to slow down the gastrointestinal muscles while it causes the muscles of the gallbladder to contract.
Therefore, it is possible that fat may worsen dyspepsia even though it doesn't cause it. Moreover, reducing the ingestion of fat might relieve symptoms. A strict low fat diet can be accomplished fairly easily and is worth trying. Additionally, there are other health-related reasons for reducing dietary fat.
Another dietary factor, fructose and fructose-related sugars, has been suggested as a cause of dyspepsia since many people do not fully digest and absorb them before they reach the distal intestine. It is diagnosed with a hydrogen breath test using fructose and treated with elimination of fructose-containing foods from the diet.
Unfortunately, fructose and its related sugars are widespread among fruits and vegetables and are found in high concentrations in many food products sweetened with corn syrup. Thus, an elimination diet is more difficult to maintain.
Patients with functional disorders, including dyspepsia, are frequently found to be suffering from depression and/or anxiety. It is unclear, however, if the depression and anxiety are the cause or result of the functional disorders or are unrelated to these disorders. Depression and anxiety are common and, therefore, their occurrence together with functional disorders may be coincidental.
Several clinical trials have shown that antidepressants are effective in IBS in relieving abdominal pain. Antidepressants also have been shown to be effective in unexplained (non-cardiac) chest pain, a condition thought to represent a dysfunction of the esophagus. Antidepressants have not been studied adequately in other types of functional disorders, including dyspepsia. It probably is reasonable to treat patients with dyspepsia with psychotropic drugs if they have moderate or severe depression or anxiety.
The antidepressants work in dyspepsia and in functional esophageal pain at relatively low doses that have little or no effect on depression. It is believed, therefore, that these drugs work not by combating depression, but in different ways (through different mechanisms). For example, these drugs have been shown to adjust (modulate) the activity of the nerves and to have analgesic (pain-relieving) effects as well.
Commonly used psychotropic drugs include the tricyclic antidepressants, desipramine (Norpramine) and trimipramine (Surmontil). Although studies are encouraging, it is not yet clear whether the newer class of antidepressants, the serotonin-reuptake inhibitors such as fluoxetine(Prozac), sertraline (Zoloft) and paroxetine (Paxil), are effective in functional disorders, including dyspepsia.
Psychological treatments include cognitive-behavioral therapy, hypnosis, psychodynamic or interpersonal psychotherapy, and relaxation/stress management. Few studies of psychological treatments have been conducted in dyspepsia, although more studies have been done in IBS. Thus, there is little scientific evidence that they are effective in dyspepsia, although there is some evidence that they are effective in IBS.
One of the leading theories for the cause of dyspepsia is abnormalities in the way gastrointestinal muscles function. The function of muscles may be abnormally increased, abnormally decreased, or it may by uncoordinated. There are medications, called smooth muscle relaxants, that can reduce the activity of the muscles and other drugs that can increase the activity of the muscles, called the promotility drugs.
Many of the symptoms of dyspepsia can be explained on the basis of reduced activity of the gastrointestinal muscles that results in slowed transport (transit) of food through the stomach and intestine. Such symptoms include nausea, vomiting and abdominal bloating.
When transit is severely affected, abdominal distention (swelling) also may occur and can result in abdominal pain. The oretically, drugs that speed up the transit of food should, in at least some patients, relieve symptoms of dyspepsia that are due to slow transit.
The number of promotility drugs that are available for use clinically is limited. Studies of their effectiveness in dyspepsia are even more limited. The most studied drug is cisapride (Propulsid), a promotility drug that was withdrawn from the market because of serious cardiac side effects. The few studies with cisapride for dyspepsia were inconsistent in their results. Some studies demonstrated benefits whereas others showed no benefit.
Cisapride was effective in patients with severe emptying problems of the stomach (gastroparesis) or severely slowed transit of food through the small intestine (chronic intestinal pseudo-obstruction). These two diseases may or may not be related to dyspepsia.
Another promotility drug that is available is erythromycin, an antibiotic that stimulates gastrointestinal smooth muscle as one of its side effects. Erythromycin is used to stimulate smooth muscles of the gastrointestinal tract at doses that are lower than those used for treating infections. There are no studies of erythromycin in dyspepsia, but erythromycin is effective in gastroparesis and probably also in chronic intestinal pseudo-obstruction.
Metoclopramide (Reglan) is another promotility drug that is available. It has not been studied, however, in dyspepsia. Moreover, it is associated with some troubling side effects. Therefore, it may not be a good drug to undergo further testing in dyspepsia.
Domperidone (Motilium) is a promotility drug that is available in the U.S., but requires a special permit from the US Food and Drug administration. As a result, it is not very commonly prescribed. It is an effective drug with minimal side effects.
Smooth muscle relaxants
The most widely studied drugs for the treatment of abdominal pain in functional disorders are a group of drugs called smooth-muscle relaxants.
The gastrointestinal tract is primarily composed of a type of muscle called smooth muscle. (By contrast, skeletal muscles such as the biceps are composed of a type of muscle called striated muscle.) Smooth muscle relaxant drugs reduce the strength of contraction of the smooth muscles but do not affect the contraction of other types of muscles.
They are used in functional disorders, particularly IBS, with the assumption (not proven) that strong or prolonged contractions of smooth muscles in the intestine-spasms-are the cause of the pain in functional disorders. There are even smooth muscle relaxants that are placed under the tongue, as is nitroglycerin for angina, so that they may be absorbed rapidly.
There are not enough studies of smooth muscle relaxants in dyspepsia to conclude that they are effective at reducing pain. Since their side effects are few, these drugs probably are worth trying. As with all drugs that are given to control symptoms, patients should carefully evaluate whether or not the smooth muscle relaxant they are using is effective at controlling the symptoms. If it is not clearly effective, the option of discontinuing the relaxant should be discussed with a physician.
Commonly used smooth muscle relaxants are hyoscyamine (Levsin, Anaspaz, Cystospaz, Donnamar) and methscopolamine (Pamine, Pamine Forte). Other drugs combine smooth muscle relaxants with a sedativechlordiazepoxide hydrochloride and clidinium bromide (Donnatal, Librax), but there is no evidence that the addition of sedatives adds to the effectiveness of the treatment.