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The Management of Nonulcer Dyspepsia

Defining DyspepsiaDyspepsia is one of the most common problems encountered in gastroenterology practice, and it accounts for 2 to 5% of primary care visits. Prevalence estimates for dyspepsia range from 12 to 45%, with an average estimate of about 25%. Although there is turnover in the dyspeptic population with time, many patients experience chronic symptoms. Dyspepsia is associated with diminished quality of life, diminished productivity, and high use of health care resources.

Defining Dyspepsia

Dyspepsia is a symptom and not a diagnosis. It can be broadly defined as pain or discomfort centered in the upper abdomen. “Centered” refers to symptoms chiefly in or around the midline and not the left or right upper quadrants. “Discomfort” refers to unpleasant feelings that stop short of being painful, including upper abdominal fullness, early satiety, bloating, nausea, and retching or vomiting. Importantly, dyspeptic symptoms are not associated with altered bowel habits, but it is recognized that dyspepsia and irritable bowel syndrome frequently coexist.

Investigated and Uninvestigated Dyspepsia

An important distinction should be drawn between patients with dyspeptic symptoms that have not been examined (uninvestigated dyspepsia) and those who have been. Investigated dyspeptics can be divided into two groups: those with an identified cause for their symptoms and those whose symptoms have either no obvious cause or a related finding of uncertain clinical significance. Examples of the former category include peptic ulcer disease, gastro-esophageal reflux disease (gastroesophageal reflux disease), or pancreaticobiliary disease. Examples of the latter include such things as delayed gastric emptying and visceral hypersensitivity

Functional Dyspepsia

Dyspeptic patients with no clear structural or biochemical explanation for their symptoms are considered to have functional dyspepsia. Functional dyspepsia is synonymous with the terms nonulcer and idiopathic dyspepsia. It is broadly defined as persistent pain or discomfort centered in the upper abdomen without organic explanation and not associated with bowel pattern. Rome II criteria specify that symptoms be present for 12 weeks in the preceding 12 months. Although this rigidity is not required in clinical practice, chronicity is an important feature of functional dyspepsia.

Functional dyspepsia is a heterogenous disorder, and currently favored mechanisms are shown in Table Potential Etiologies in Functional Dyspepsia. Attempts to elicit meaningful etiologies have resulted in the creation of subgroups defined using various symptom criteria. The utility of classifying functional dyspeptics, whether based on symptom clusters or dominant symptoms, remains controversial, because evidence supporting improved clinical outcomes using such an approach is lacking. Perhaps the most relevant change is that the reflux-like subgroup has been abandoned. These patients should be regarded as having gastroesophageal reflux disease until proven otherwise. It is worth noting that a subset of patients with gastroesophageal reflux disease may present with upper abdominal pain or discomfort in the absence of classic heartburn. Currently, three functional dyspepsia subgroups are recognized according to Rome II criteria. Ulcer-like dyspepsia has pain as the predominant symptom. Dysmotility-like dyspepsia has an unpleasant nonpainful sensation, such as fullness, bloating, early satiety, or nausea as the predominant symptom. Finally, patients with unspecified dyspepsia do not fulfill criteria for either ulcer-like or dysmotility-like dyspepsia.

Table. Potential Etiologies in Functional Dyspepsia

Visceral hypersensitivity
Impaired gastric emptying
Impaired postprandial fundic relaxation
Antral hypomotility
Gastric dysrhythmias
Small bowel dysmotility
Vagal neuropathy
Duodenal acid hypersensitivity
Psychosocial disturbances

Approach to the Patient with Functional Dyspepsia

The Management of Nonulcer DyspepsiaOnly 20 to 25% of people with dyspeptic symptoms will seek care. Importantly, symptoms do not appear to discriminate dyspeptic consulters from nonconsulters. Dyspeptics who consult are characterized by greater worry over serious illness or cancer, heightened levels of anxiety, depression, and illness behavior, as well as recent traumatic life events. Additionally, they tend to employ more confrontative rather than social coping styles. In short, although physicians focus most of their efforts on the patient’s symptoms, it is not necessarily the symptoms that lead people to consult. To be effective in the examination and management of these patients, clinicians must pay attention to the patients as well as to the patients’ digestive tracts.


Consultation with a patient with nonulcer dyspepsia should address several important issues, including the following:

1.    Determine the patient’s agenda. Understand why they are seeking care at this time. Address any concerns or fears that they may have regarding their symptoms.

2.    Identify triggering or exacerbating factors. These include foods, medicines, situations, and life events. If possible, define the events surrounding symptom origination. Functional symptoms often begin or recur at times of significant psychosocial stress.

3.    Evaluate just enough. The evaluation should address relevant clinical issues and provide diagnostic certainty. It should also, within reason, address any particular concerns the patient might have. Repetitive studies done for persistent symptoms are rarely helpful. In fact, a never-ending diagnostic evaluation only adds uncertainty to the situation and promotes the “sick role.”

Table. Diagnostic Measures in Functional Dysplasia

Diagnostic Measures Utility
History and examination Critical. Determines symptom etiologies, triggers and associations. Identifies patient agenda and concerns. Assesses psychosocial issues. Establishes therapeutic relationship
Upper endoscopy Ideally done during a symptomatic period off medications
Helicobacter pylori testing Routinely done but eradication of little value in nonulcer dyspepsia
Ultrasonography Routinely done but the finding of cholelithiasis in the setting of dyspepsia may raise more questions than it answers.
Psychometric testing Rarely done in practice. Often useful in refractory patients
Gastric emptying study Clinical utility not defined. Abnormal study does predict response to prokinetics
Electrogastrogram Clinical utility not defined
Gastroduodenal manometry Rarely helpful unless pseudo-obstruction or partial small bowel obstruction suggested on clinical grounds
Gastroduodenal sensory testing Clinical utility not defined. Hypersensitivity versus hyper viqilance needs to be clarified

4.    Formulate a treatment plan in which the patient takes an active role in planning and implementation. A critical determinant of successful outcomes is that the patient understands and accepts the diagnosis and treatment. This also ensures that educational and patient issues are effectively addressed. The quality of the physician-patient relationship remains a key determinant of clinical success in the treatment of functional digestive disorders.

5.    Follow-up is essential. Seeing the patient back facilitates the physician-patient relationship and provides an opportunity to gather more information about the patient and their illness. It also allows the physician and patient to review and modify the treatment plan as needed. Very often subsequent visits are more rewarding in eliciting crucial psychosocial information as the patient and physician become more trusting and open with one another.

6.    Take a psychosocial history and examine for psychiatric illness. Taking a psychosocial history is not something that is emphasized or even routinely discussed in most gastroenterology training programs. It is, however, an important diagnostic and therapeutic tool. Commonly helpful questions concerning psychosocial issues are shown in Table Useful Questions Regarding Psychosocial Factors in a Patient’s Illness.

TABLE. Useful Questions Regarding Psychosocial Factors in a Patient’s Illness

1. Is the patient’s illness acute or chronic? Chronic illness has a greater potential for psychosocial concomitants.
2    What is the patient’s illness history? A history of multiple vague complaints, multiple procedures, and poor responses to treatment should raise suspicion that psychosocial factors are contributing.
3. Why is the patient presenting now? Psychosocial factors often influence care seeking.
4.   Is there a psychiatric diagnosis? ldentifying such a diagnosis that is amenable to treatment can improve outcomes.
5. Is there a history of abuse? Abusive experiences are associated with poorer outcomes and are often undisclosed unless sought in a supportive, empathetic fashion.
6. Is there evidence of unhelpful illness behavior or coping style? Examples include overly demanding requests for care and unrealistic expectations to find organic disease or a cure.
7.   What are the family dynamics around the illness? Are there counterproductive family interactions, such as marital power struggles and separation issues with parents and children, that may manifest through illness?
8.   What are the patient’s supports? Strong social support is important for clinical improvement.

Specific Investigations in Nonulcer Dyspepsia

Specific Therapies For Nonulcer Dyspepsia

A wide variety of agents have been used to treat nonulcer dyspepsia. Therapeutic efficacy for most agents is limited and biomarkers to predict responses to specific agents are largely lacking. There are however some useful observations that may improve clinical outcomes.

Acid Suppression

Antisecretory medications are the most widely used agents in the treatment of nonulcer dyspepsia. A number of studies have evaluated the efficacy of H2 receptor antagonists (H2RAS) and several meta-analyses have analyzed these trials. Many of the studies with H2RAS have methodological flaws in either study design or enrollment criteria. Epigastric pain and postprandial fullness are the symptoms that are the most relieved. H2RAS provide a modest benefit over placebo with a relative symptom reduction of about 22%. Comparisons of  H2RAS with prokinetics or proton pump inhibitors (proton pump inhibitors) have not shown much advantage for one therapeutic class over the other. Given the low cost and safety of H2RAS, these agents remain reasonable therapeutic agents in the treatment of nonulcer dyspepsia.

There are actually fewer data supporting the use of proton pump inhibitors in the treatment of functional dyspepsia. Omeprazole has been compared with placebo in a combined analysis of two large trials. Both 10 mg and 20 mg doses of omeprazole were superior to placebo in patients with refluxlike and ulcer-like dyspepsia. Omeprazole provided a net therapeutic gain of about 8% beyond placebo. Omeprazole was not better than placebo in patients with dysmotility-like symptoms. Another large trial compared lansoprazole (Prevacid ) in 15 mg and 30 mg doses with placebo and failed to find significant benefit in any dyspepsia subgroup.

Current Use

Psychological Interventions

Psychological interventions in patients with irritable bowel syndrome have been evaluated, and a recent systematic analysis supports their efficacy. Hypnotherapy and cognitive behavioral therapy are the modalities best studied. A recent study showed that hypnotherapy was superior to supportive and medical therapies at both 16 and 56 weeks. The results were quite striking with net therapeutic gains over medical therapy of 30% for symptoms and 24% for quality of life. It seems likely that psychological interventions will prove to be highly effective in functional digestive disorders, and we have incorporated both behavioral therapy and hypnotherapy into our practice. More rigorous study is needed particularly in the setting of nonulcer dyspepsia. The clinical utility of this intervention will also be highly dependent on the availability of behavioral health specialists to provide the service and third party payers to reimburse for what can be a costly treatment.

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