Current and future treatment management strategies for gastroparesis

ABSTRACT

Introduction: Gastroparesis (GP) is a debilitating condition characterized by delayed gastric emptying (GE) after gastric outlet obstruction has been excluded. GP is a debilitating condition affecting more than 10 million patients, which is approximately 3% of US population. In this review, we will elaborate on the current treatment options for GP, recent advancement in its management and its future directions.

Areas covered: Combination of antiemetics and prokinetics is the current management strategy. The only Food and Drug Administration (FDA) approved agent for GP is Metoclopramide but it has a black box warning for tardive dyskinesia. Several new drugs with different mechanism of action are currently being investigated with encouraging efficacy and minimal side effects. Also, advancement in non-pharmacological management such as gastric neurostimulator and per-oral endoscopic pyloromyotomy (G-POEM) has shown benefit in GP.

Expert opinion: Current management of GP continues to be a challenge with only one approved drug (metoclopramide). However, many new potential treatment options are under development, with advances in understanding the pathophysiology of GP. Other future treatment possibilities involve advances in regenerative medicine, particularly stem cell-based transplantation targeting ICC depletion and enteric nerve damage.

KEYWORDS:

• Gastroparesis
• delayed gastric emptying
• nausea
• vomiting
• enteric nervous system
• gastric electrical stimulation

Article highlights

• Medical management should be initiated in all the patients with symptomatic GP. New pharmacological therapies are rapidly evolving and will be reaching FDA approval stage, which will provide a new and better ‘menu’ of effective prokinetics.

• Antiemetic therapy is the first line of therapy to establish control of the main symptoms- nausea & vomiting. There are several agents available having different receptor targets in the chemoreceptor trigger zone. Strategic utilization of these agents alone or in combination is the current recommendation at the same time combining a prokinetic medication can achieve a more sustained symptom control.

• Our recent increased understanding of pathophysiology in GP has extended beyond the observations of ICC depletion to understanding the unappreciated crucial role of pyloric damage in the pathophysiology of GP. Armed with this new understanding of the pathophysiology and specifically targeting the pylorus, we now have the surgical and endoscopic tools in hand as well as the clinical outcome data to confidently state that we have and can continue to successfully overcome GP.

• Certainly, it is recommended to actively initiate medical management, but with knowledge that when responses are suboptimal, there should be no hesitation in turning to ‘the final solution’ for GP, which is placement of a gastric neurostimulation for nausea control combined with a surgical pyloroplasty to accelerate and normalize GE.

• The focus is currently on the prevention of GP by drilling down to the molecular level in the smooth muscle. New knowledge from M1 and M2 macrophages as well as inflammatory pathways has led to further understanding of how to prevent ICC depletion, damage to the enteric nervous system and preserve nitric oxide function.

• It is very important to recognize and thank the National Institutes of Health for their decision to fund Centers of academic excellence that constitute the Clinical Gastroparesis Consortium. Over the past 12 years, the consortium has made seminal contributions to the advancement in this field. We look forward to their continued leadership in future discoveries, which will achieve the goal of cure and prevention of GP over the next 5 years.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.