Dyspepsia (cont.)
How is dyspepsia (indigestion) treated?
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. Therefore, 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. Therefore, 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 (antidepressants)
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.
Education
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.
Diet
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.
Psychotropic drugs
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
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.
Promotility drugs
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. (It is clear, as discussed
previously, that there are other causes of these symptoms in addition to slowed
transit.) 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. (Early satiety is unlikely to be a function of
slowed transit because it occurs too early for slowed transit to have
consequences.) Theoretically, 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 sedative chlordiazepoxide hydrochloride and clidinium bromide
(Donnatal, Librax), but there is no evidence that the addition of
sedatives adds to the effectiveness of the treatment.
Next: What is a reasonable approach to the diagnosis and treatment of dyspepsia (indigestion)? »
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