Efficacy of Drugs for Functional Dyspepsia

Alimentary Pharmacology & Therapeutics:

Functional dyspepsia is characterised by troublesome early satiety, fullness, or epigastric pain or burning. It can easily be overlooked as the symptoms overlap with gastro-oesophageal reflux disease and irritable bowel syndrome.

It affects 10% of the population and is more prevalent in women.

The pathophysiology of functional dyspepsia is not completely understood. It is thought to be associated with upper gastrointestinal inflammation and motility disturbances, which may be triggered by an infectious or allergenic agent, or a change in the intestinal microbiome. Slow gastric emptying occurs in 20% of cases.

There are two subtypes of functional dyspepsia, although these often overlap in practice. The largest groups (70%) have early satiety or postprandial fullness, termed postprandial distress syndrome. The other group experience ulcer-like pain or burning, termed epigastric pain syndrome.

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While functional dyspepsia is distressing and affects quality of life, it has no long-term impacts on mortality.

There are many treatment options available, with varying levels of evidence of efficacy. These include reassurance, dietary modification, acid suppression, prokinetic drugs including fundic relaxors, tricyclic antidepressants, rifaximin and psychological therapy.

The authors conducted a systematic review and meta-analysis of drugs used for functional dyspepsia. Overall, 71 randomized controlled trials were included, with over 19,000 study participants. Efficacy was determined as the relative risk of participants remaining symptomatic after treatment.

Tricyclic antidepressants were second in efficacy in the analysis; however, they were first when only higher-quality trials were included. Multiple other drugs were analyzed, and all were superior to placebo.

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Diagnosis

Diagnosis is clinical. A typical history of long-standing troublesome early satiety and postprandial fullness is sufficient to make a clinical diagnosis and commence treatment, but often gastroscopy is required. Any of the following red flag symptoms should prompt endoscopy:

new onset in older age
unintended weight loss
vomiting
bleeding
iron deficiency anaemia
family history of upper gastrointestinal cancer
progressive dysphagia or odynophagia.

It is otherwise reasonable to screen for H. pylori infection by breath or stool antigen test and treat positive cases. Non-steroidal anti-inflammatory drugs should be stopped before either investigation or an empiric trial of therapy, usually a proton pump inhibitor for 2–4 weeks, in those who are still symptomatic.

Treatments

There are many treatment options available for functional dyspepsia, with some being more effective than others. Many patients will respond to non-pharmacological management and drug therapy should be reserved for refractory cases.

Abstract

Background: Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.

Aim: To perform a systematic review with network meta-analysis to resolve this uncertainty.

Methods: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.

Results: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy, and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy, trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.

Conclusions: TCAs, histamine-₂ receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.