A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD)

ABSTRACT

Introduction: Medical therapy of gastroesophageal reflux disease (GERD) is based on the use of proton pump inhibitors (PPIs) as first choice treatment. Despite their effectiveness, about 20–30% of patients report an inadequate response and alternative drugs are required.

Areas covered: This review provides an overview of current pharmacotherapy for treating GERD by showing the results of PPIs, reflux inhibitors, antidepressants and mucosa protective medications.

Expert opinion: Medical therapy of GERD does not definitely cure the disease, because even PPIs are not able to change the key factors responsible for it. However, they remain the mainstay of medical treatment, allowing us to alleviate symptoms, heal esophagitis and prevent complications in the majority of cases. Nevertheless, many patients do not respond, because acid does not play any pathogenetic role. Prokinetics and reflux inhibitors have the potential to control motor abnormalities, but the results of clinical trials are inconsistent. Antidepressant drugs are effective in specific subgroups of NERD patients with visceral hypersensitivity, but larger, controlled clinical studies are necessary. Protective drugs or medical devices have been recently adopted to reinforce mucosal resistance and preliminary trials have confirmed their efficacy either combined with or as add-on medication to PPIs in refractory patients.

KEYWORDS:

• Antidepressants
• GERD
• medical therapy
• mucosa protective medications
• PPIs
• prokinetics
• reflux inhibitors

Article Highlights

• Current drugs used for treating GERD are not able to definitely cure the disease, which is substantially due to multiple motor alterations.

• Despite the lack of gastric acid hypersecretion, PPIs remain the mainstay of medical therapy of GERD. They permit to control symptoms, heal esophagitis, prevent complications and are also able to maintain patients in clinical and endoscopic remission in the long-term.

• However, 20–30% of GERD typical symptoms do not respond to PPIs, because acid does not play any pathogenetic role in inducing them.

• Patients with non-erosive reflux disease (NERD) are the most frequent phenotype of GERD (up to 70%) and many of them have symptoms due to visceral hypersensitivity rather than to acid.

• Antidepressants are effective in alleviating symptoms in the above patients, but this benefit should be confirmed by larger, controlled clinical trials.

• Prokinetics and reflux inhibitors have shown poor and inconsistent results in controlled clinical studies, although they should be the most indicated drugs to change the motor alterations implicated in GERD pathogenesis.

• Recently, the reinforcement of mucosa resistance has been considered as a new therapeutic target, overlooked in the past. Several drugs or medical devices have bioadhesive properties and the preliminary controlled trials have shown that they can improve symptoms when used in combination or as add-on medication to PPIs in refractory GERD patients. More clinical data are needed.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.

Notes on contributors

Edoardo Savarino

- Edoardo Savarino, MD: writing of the manuscript, approving final version

Patrizia Zentilin

- Patrizia Zentilin, MD, PhD: data collection and analysis, writing of the manuscript, approving final version

Elisa Marabotto

- Elisa Marabotto, MD, PhD: data collection and analysis, writing of the manuscript, approving final version

Giorgia Bodini

- Giorgia Bodini, MD, PhD: data collection, writing of the manuscript, approving final version

Marco Della Coletta

- Marco della Coletta, MD, PhD: data collection, writing of the manuscript, approving final version

Marzio Frazzoni

- Marzio Frazzoni, MD, PhD: data collection, writing of the manuscript, approving final version

Nicola de Bortoli

- Nicola de Bortoli, MD, PhD: data collection, writing of the manuscript, approving final version

Irene Martinucci

- Irene Martinucci, MD, PhD: data collection, writing of the manuscript, approving final version

Salvatore Tolone

- Salvatore Tolone, MD, PhD: data collection, writing of the manuscript, approving final version

Gaia Pellegatta

- Gaia Pellegatta, MD: data collection and analysis, approving final version

Vincenzo Savarino

- Vincenzo Savarino, MD: writing of the manuscript, approving final version