Acid suppressive therapy may be of benefit in patients with functional dyspepsia and the benefit appears greatest in patients with ulcer-like symptoms. A 2 to 4 week trial of antisecretory therapy at standard doses is reasonable. Therapy should be discontinued if there is no response. Despite a lack of support from existing literature, most gastroenterologists would empirically use proton pump inhibitors rather than H2RAS. Because empiric acid suppression is used to treat both gastroesophageal reflux disease presenting as dyspepsia as well as true nonulcer dyspepsia, this approach is reasonable.
H. pylori Eradication
A recent meta-analysis reported that eradicating H. pylori offers a net therapeutic gain of about 9% beyond placebo. A second meta-analysis did not find significant improvement in symptoms following eradication. The disparate results stem from the numbers of trials included. Unfortunately, there do not appear to be any clinical predictors of response to H. pylori eradication. The decision to test patients with nonulcer dyspepsia for H. pylori infection remains somewhat controversial. If a patient is found to be infected, treatment should be offered but the likelihood of clinical improvement is small.
The most widely studied prokinetic in the treatment of nonulcer dyspepsia is cisapride, but it is currently available in the United States only through an onerous limited access protocol. Although cisapride appeared significantly better than placebo in reducing dyspeptic symptoms, many of the available trials were small in size and publication bias may have influenced results. Comparisons of cisapride with metoclopramide or domperidone or metoclopramide with domperidone have not demonstrated the superiority of one agent over another. Motilin agonists have not been well studied, but a recent trial with ABT-229 found it to actually be inferior to placebo in providing symptom relief.
Domperidone can be obtained from non-US-based pharmacies, often without a prescription. It may also be obtained from compounding pharmacies in the United States with a prescription, but it tends to be much more expensive. Because domperidone has both antiemetic and prokinetic effects without central nervous system toxicity, it is often helpful in patients with dysmotility-like dyspepsia. The starting dose is 10 mg before meals and at bedtime. Although metoclopramide (Reglan) remains our first line prokinetic because of availability and expense, domperidone is used in patients who either do not respond to or do not tolerate metoclopramide. To date, there are no published trials of the partial 5-HT4 agonist tegaserod in the treatment of nonulcer dyspepsia, but this agent may have efficacy in a subset of patients.
Antidepressants are commonly used in the treatment of functional digestive disorders and appear to be beneficial. In a small trial of seven patients, Mertz and colleagues (1998) showed that 50 mg of amitriptyline at bedtime significantly reduced symptoms of nonulcer dyspepsia. Similar results have been seen by Tanum and Malt (1996) with the tetracyclic agent mianserin. Interestingly, a response to this agent is predicted by both results of a/en –fluramine challenge and certain personality constructs.
These personality traits include low levels ofneuroticism, as well as low levels of hidden aggression. Thus, in contrast to acid suppression, H. pylori eradication, and prokinetics, there are biomarkers that predict a response to antidepressants. At present, there are no published data for selective serotonin reuptake inhibitors in nonulcer dyspepsia, although studies are underway. Paroxitene (Paxil) has been shown to enhance meal-induced relaxation of the fundus, but sertraline (Zoloft) exerts no effect on gastric compliance or sensitivity.
Anxiolytics are generally avoided in the management of nonulcer dyspepsia because of the potential for habituation and abuse. There are, however, two scenarios in which these agents appear helpful. The first is in the management of patients with anxiety or panic disorders who have prominent dyspeptic features. Anxiety and panic may be associated with both symptom generation and enhanced symptom perception and decreased symptom tolerance. Additionally, a subset of patients with panic disorders may present with digestive symptoms (most often nausea) in the absence of more classic anxiety symptoms. The SCL-90-R is useful in identifying these patients, as are two other instruments, the Beck Anxiety Index and Spielberger State-Trait Anxiety Index.
The second group that may benefit from anxiolytics is made up of patients with persistent nausea and vomiting. Nausea is an easily conditioned behavior, as has been repeatedly seen in patients with chemotherapy-induced nausea and vomiting. Lorazepam (Ativan) is often effective in treating these patients because of its antiemetic and anxiolytic properties. Buspirone (BuSpar) is an anxiolytic that has fallen from favor in psychiatry but has gained favor in gastroenterology. It is a 5-HTia agonist that causes fundal relaxation. In healthy controls it has been shown to significantly decrease postprandial symptom scores. Although therapeutic trials are needed, our anecdotal experience with this agent in upper abdominal bloating and early satiety has been quite positive. Other fundal relaxants include sumatriptan (Imitrex), tegaserod (Zelnorm), paroxitene (Paxil), and citalopram (Celexa). All require clinical evaluation.