Brooks D. Cash, MD, FACP, FACG

Disclosures

December 12, 2002

In This Article

Therapy for Functional Dyspepsia

One of the critically important features of successful treatment for functional gastrointestinal disorders, such as functional dyspepsia, is a sound patient-physician relationship. The physician should acknowledge that the symptoms that the patient is experiencing are real and, understandably, bothersome. The patient's concerns should be investigated and discussed. The latter should be followed by education and reassurance that functional dyspepsia is both common and not life-threatening. Setting reasonable treatment goals and empowering the patient to take responsibility for his/her own healthcare are also important features of supportive care. The latter can be done by having the patient use a symptom diary that allows for self-examination for possible triggers or behaviors that may exacerbate symptoms.

Antisecretory agents (H2RAs or PPIs) and HP eradication therapy have a central role in the initial treatment approach to patients with uninvestigated dyspepsia. In patients with functional dyspepsia in whom acid hypersensitivity may play a role, PPIs are the antisecretory agents of choice because they have been shown in many studies of gastroesophageal reflux disease to provide a more robust and prolonged acid suppression than H2RAs. Although H2RAs remain the primary antisecretory therapies of choice for many primary care physicians, a Cochrane review of randomized, controlled trials demonstrated the superiority of PPI therapy over H2RA therapy, with symptom relief in the 40% to 70% range.[23] Among the 5 available PPIs, none has proven to be more effective than any other as a treatment for the various symptoms of dyspepsia. Most patients will not respond to these initial treatment efforts.

Promotility agents available in the United States include metoclopramide and erythromycin. Neither of these drugs has been proven effective for functional dyspepsia, and they are limited by potentially serious adverse effects, and, in the case of erythromycin, by the development of tachyphylaxis.

Two additional promotility agents that have shown promise for functional dyspepsia are cisapride and domperidone. Cisapride stimulates gastrointestinal motility through its action as a partial 5HT4 agonist. Domperidone is a peripherally acting dopamine antagonist that is known to promote gastric emptying and antropyloric motility. Both of these drugs have been shown to be at least partially beneficial in a subset of patients with functional dyspepsia. A recent meta-analysis of placebo-controlled trials by van Zanten and colleagues[24] found that both agents were effective in achieving global improvements in dyspepsia symptoms as well as in individual symptoms such as bloating or early satiety. An important caveat to this conclusion is that the outcomes from many of the trials included in this meta-analysis were derived from the investigators rather than from the patients. In trials of therapy for functional gastrointestinal disorders, the Rome II consensus opinion is that outcomes should be patient-derived and should focus on global assessment of well-being.[25] Unfortunately, neither of these drugs is available in the United States. Cisapride was voluntarily withdrawn from the market due to concerns about QTc prolongation and serious cardiac side effects, and domperidone has not been approved by the Food and Drug Administration for use in this country.

Clinical trials of other promotility agents, such as motilin agonists and partial 5HT4 agonists (tegaserod) that do not have the potential cardiac effects of cisapride, are under way and have shown some promise for patients with functional dyspepsia.[26]

Impaired gastric accommodation has recently received increasing attention as a putative mechanism for dyspepsia symptoms in a subset of patients. Tack and colleagues[27] have identified impaired accommodation of the gastric fundus in response to a meal in up to 40% of patients with functional dyspepsia. This impaired accommodation was uniquely associated with early satiety and weight loss, but was not related to delayed gastric emptying or hypersensitivity to gastric distension. Moreover, administration of 5HT1 agonists such as sumatriptan and buspirone have demonstrated an ability to induce relaxation of the proximal stomach and thus possibly reduce the unpleasant symptoms that many patients with functional dyspepsia experience in response to gastric distension.[28,29] The latter remains to be proven in rigorous clinical trials. Because of the lack of convincing evidence supporting their use, 5HT1 agonists should probably be used as second-line agents for functional dyspepsia and will likely be most beneficial for the subset of patients reporting early satiety as their primary symptom. Buspirone, because of its more attractive safety profile compared with sumatriptan and its possibly beneficial anxiolytic effects, should be the agent of choice among this class of medications.

Psychologic factors often can be identified in patients with functional gastrointestinal disorders. These factors include life stresses and events as well as higher scores for traits such as anxiety, tension, and neuroticism.[30] Although patients often do not demonstrate these traits through impaired social functioning, they may manifest through such behavior as healthcare seeking and may be responsible for visceral sensation-processing alterations via the central and enteric nervous systems.

Antidepressant drugs. Antidepressant therapies have been used in other functional gastrointestinal disorders such as IBS for several years with variable degrees of success. In low doses, antidepressant drugs, especially those in the tricyclic antidepressant class, appear to moderate visceral hypersensitivity and mediate nociception. Data supporting the use of antidepressant therapy for functional dyspepsia are scarce. A meta-analysis of antidepressant therapy for functional gastrointestinal disorders conducted by Jackson and colleagues[31] demonstrated a modest treatment benefit associated with the tricyclic antidepressants. However, these data must be considered with caution because the trials that were analyzed also included patients with IBS, and the methodology of many of the studies was flawed.

Cognitive psychotherapy. Psychotherapy has been examined in patients with functional gastrointestinal disorders. Most of these studies looked at the effects of this psychologic approach on IBS symptoms. Different psychotherapeutic modalities used to treat functional gastrointestinal disorders include insight-oriented psychotherapy, relaxation and stress-management training, cognitive-based behavioral therapy, and biofeedback.[32] The most studied of these techniques is cognitive-behavioral therapy. This form of psychotherapy is designed to teach patients how to identify their maladaptive behavior and how to manage their responses to emotional and life stresses. Investigations of psychotherapy for functional dyspepsia have used a variety of approaches and comparators.

Haug and colleagues[33] randomized 100 patients to either cognitive psychotherapy or no therapy and found that the patients who received psychotherapy experienced significant improvement in symptoms such as bloating, epigastric pain, and nausea. Mine and colleagues[34] randomized 198 patients with functional dyspepsia to a combination of medical, psychiatric, and psychotherapeutic treatments vs medical therapy alone. They found that the multimodality therapeutic regimen afforded significantly improved outcomes over medical therapy alone. Recently, Hamilton and associates[35] sought to determine if brief psychodynamic-interpersonal psychotherapy was superior to reassurance alone. At the end of the treatment course, patients in the psychotherapy group had significant symptom reduction compared with the group treated with reassurance (supportive therapy) alone. At 1 year, however, patients in each treatment group had similar symptom scores. A post-hoc analysis at 1 year, removing patients with severe heartburn symptoms, indicated a potential benefit for the psychotherapy group. Thus, it is widely recognized that psychologic factors can be identified in patients with functional gastrointestinal disorders such as functional dyspepsia.

Although data regarding the effectiveness of psychotherapeutic therapies for dyspepsia are still too sparse to draw absolute conclusions, it does appear that addressing life stresses and improving coping mechanisms can be a useful adjunct to traditional therapies once organic gastrointestinal disease has been excluded.

Given the limited efficacy of conventional medical therapy for functional dyspepsia, patients frequently seek alternative medical approaches. The use of such alternative therapies has dramatically increased during the last decade. In 1997, it was estimated that 42% of the US population used some alternative medicine therapies, and out-of-pocket expenses totaled more than $12 billion.[36]

Common alternative therapies include acupuncture, massage therapy, herbal remedies, hypnotherapy, therapeutic touch, aromatherapy, and color therapy. There have been very few methodologically acceptable alternative medicine trials for functional dyspepsia. A recent systematic review found only 3 trials of herbal therapies for patients with functional dyspepsia.[37] One trial reported significant benefit in overall well-being associated with peppermint oil extract.[38] Two other trials evaluated traditional Chinese herbal therapies and reported associated treatment benefits in this setting.[39,40] It is important to note that all of these trials were limited by their small sample sizes, short duration, and lack of validated symptom-assessment tools. Thus, at present, there is insufficient evidence to recommend the routine application of alternative medicine therapies for functional dyspepsia.

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