Neuromodulation for gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a prevalent chronic condition characterized by recurrent reflux of stomach contents into the esophagus, leading to troublesome symptoms such as heartburn, regurgitation, and dyspepsia. Despite the availability of various treatment options, including lifestyle modifications, medications, and surgical procedures, none of the current therapies comprehensively target the multiple pathophysiological mechanisms involved in GERD. This systematic review by Woo et al. (2023) evaluated the efficacy, mechanisms, and safety of three neuromodulation therapies for GERD: lower esophageal sphincter (LES) electrical stimulation (LES-ES), transcutaneous electrical acustimulation (TEA), and manual acupuncture (MA).

Methods

The authors conducted a systematic literature review following the PRISMA guidelines. They searched Medline (Ovid), Embase, and PubMed for scientific papers published between 2003 and 2023, using relevant keywords to identify studies evaluating the three neuromodulation therapies. Studies were assessed for inclusion and exclusion criteria using the Covidence systematic review software. Only randomized controlled trials (RCTs) with sham-controlled groups were included for TEA and MA, while for LES-ES, open-label studies registered on ClinicalTrials.gov were considered due to the invasive nature of the therapy.

Results

The analysis included 13 clinical studies: 4 on LES-ES, 5 on TEA, and 4 on MA. All evaluated studies demonstrated significant beneficial effects on GERD symptoms, using patient-completed questionnaires, objective 24-hour esophageal pH measurements, and patient-reported use of proton pump inhibitors (PPIs). Specifically:

• LES-ES: Two pilot clinical studies (NCT01578642 and NCT02441400) showed significant improvements in GERD symptoms, as measured by the GERD-HRQL score, with up to 79% reduction in symptom scores post-treatment. LES-ES was associated with improved mental and physical health, increased patient satisfaction, and reduced PPI use.
• TEA: Randomized trials demonstrated that TEA significantly improved esophageal motility, gastric motility, and parasympathetic activity, which are key pathophysiological factors in GERD. TEA also resulted in symptom relief and reduced PPI usage.
• MA: Studies showed that MA significantly improved GERD symptoms compared to standard therapy or sham controls. However, the mechanisms underlying MA's effects were not as clearly elucidated as for TEA and LES-ES.

None of the evaluated neuromodulation methods produced severe adverse effects, suggesting a favorable safety profile.

Discussion

The results of this systematic review indicate that neuromodulation therapies are effective in treating GERD symptoms and addressing key underlying pathophysiologies. LES-ES, TEA, and MA each demonstrated significant benefits, with improvements in symptom scores, esophageal and gastric motility, and quality of life. Importantly, these therapies showed a favorable safety profile, with no severe adverse effects reported.

Neuromodulation therapies offer promising alternatives to existing GERD treatments by addressing multiple pathophysiological mechanisms. LES-ES, in particular, has the potential to enhance LES pressure and improve esophageal barrier function, while TEA and MA may influence esophageal and gastric motility through modulation of neural pathways. The invasive nature of LES-ES necessitates further investigation, particularly in large-scale, sham-controlled trials to confirm its efficacy and safety.

Conclusions

In conclusion, the cumulative evidence from the evaluated studies suggests that neuromodulation therapies are effective in treating GERD symptoms and underlying pathophysiologies, making them valuable options for individualized GERD treatment. Future research should focus on clarifying the mechanisms of action and optimizing the delivery of these therapies to improve patient outcomes.

Full text

https://www.xiahepublishing.com/2994-8754/JTG-2023-00042

The study was recently published in the Journal of Translational Gastroenterology.

Journal of Translational Gastroenterology (JTG) dedicates to improving clinical diagnosis and treatment, advancing understanding of the molecular mechanisms, and promoting translation from bench to bedside of gastrointestinal, hepatobiliary, and pancreatic diseases. The aim of JTG is to provide a forum for the exchange of ideas and concepts on basic, translational, and clinical aspects of gastroenterology, and promote cross-disciplinary research and collaboration.

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