What’s new in the management of gastroparesis?
First, there is increased recognition that the symptoms of gastroparesis may result not only from delayed gastric emptying, but also from several motor or sensory disorders of the upper gut, particularly the stomach. Hence, getting the right diagnosis for the patient’s symptoms is an essential first step. The classical diagnosis of gastroparesis is based on the combination of symptoms of gastroparesis, absence of gastric outlet obstruction or ulceration, and delay in gastric emptying. Similar symptoms may result from impaired gastric accommodation.
In a cohort of 1,287 patients presenting to a tertiary care center with upper gastrointestinal symptoms, there was an approximately equal number with delayed gastric emptying, impaired gastric accommodation, a combination of both or absence of both.1 This is consistent with the recognition that “gastroparesis and related disorders” represent a broader spectrum of gastric neuromuscular dysfunction that may present with prominent symptoms such as early satiety and postprandial fullness; these symptoms may result from impaired gastric accommodation, in addition to delayed gastric emptying. This reflects the overlap of “gastroparesis” with functional dyspepsia. Impaired gastric accommodation may be recognized with validated methods where available (SPECT and MRI), or with screening tests such as the size of the proximal stomach on the gastric scintiscan taken immediately after radiolabeled meal ingestion, or by means of a water load or nutrient drink test.
Getting the right diagnosis for the patient’s symptoms is an essential first step.
A second advance is the recognition that gastroparesis results from iatrogenic causes, including bariatric and other gastric surgery and, more commonly, from medications. The two most relevant drug classes responsible for gastroparesis are all opioids and anti-diabetic medications such as pramlintide and GLP-1 agonists (e.g. exenatide and liraglutide), but not dipeptidyl peptidase IV inhibitors such as vildagliptin and sitagliptin.
A third advance in gastroparesis is the application of new medical treatments which are on the horizon or are used off label to target these underlying mechanisms. Medications should be adjuncts to dietary changes: a highfat, solid meal increased overall symptoms among individuals with gastroparesis, and a small particle size diet reduced upper gastrointestinal symptoms (nausea, vomiting, bloating, postprandial fullness, regurgitation and heartburn) in patients with diabetic gastroparesis.
New drugs for gastroparesis
Relamorelin is a ghrelin receptor agonist that stimulates gastric body and antral contractions, accelerates gastric emptying, and has been shown in phase 2A and 2B studies to increase gastric emptying of solids and reduce symptoms, particularly nausea, fullness, bloating and pain.2 Relamorelin is currently being tested in phase 3 trials which should also provide information on optimal dose of this subcutaneous treatment.
Prucalopride (1-2mg/day), a 5-HT4 receptor agonist, is approved in most countries (other than the U.S.) for the treatment of chronic constipation. It accelerates gastric emptying and was shown in a preliminary report to relieve symptoms in 28 patients with idiopathic gastroparesis.
New drugs for impaired gastric accommodation
The acetyl cholinesterase inhibitor, acotiamide, enhances gastric accommodation, relieves dyspeptic symptoms and is approved in Japan for treatment of dyspepsia.
Approved drugs used off label
Although not proven efficacious in a randomized, controlled trial in patients with gastroparesis, nortriptyline (tricyclic antidepressant) is used for relief of pain. In a study conducted in patients with functional dyspepsia, amitriptyline improved symptoms in patients who did not have delayed gastric emptying, and it modestly improved sleep quality. The typical doses for both drugs are 25mg/day.
Mirtazapine (15mg/day), with its central adrenergic and serotonergic activity, provides symptom relief for patients with functional dyspepsia and weight loss, a condition with significant overlap with gastroparesis.
Buspirone (7.5-15mg daily or bid), a 5-HT1A agonist, enhances gastric accommodation and reduces postprandial symptoms in patients with functional dyspepsia.
Aprepitant (125mg/day) was efficacious in the treatment of nausea in some patients with gastroparesis and related disorders.3 It does not change gastric emptying, but increases fasting and postprandial (accommodation) gastric volumes.
Open label experience with intra-pyloric BOTOX injection in 179 patients with gastroparesis was associated with decrease in gastroparesis symptoms one to four months after pyloric BOTOX in 92 patients (51.4 percent). Improved response to BOTOX was observed in those who received 200U (rather than 100U), females, under 50 years of age, and non-diabetic, nonpostsurgical gastroparesis patients.
- It is important to treat patients with upper gastrointestinal symptoms suggestive of gastroparesis based on the right diagnosis, excluding iatrogenic disease and use of opioids.
- New pharmacologic agents are promising; meanwhile off label use of approved medications anchors current management in addition to dietary interventions.
- Pyloric interventions, including endoscopic pyloroplasty, require further validation.
Dr. Camilleri has received research support for studies with Relamorelin. Dr. Camilleri is vice chair of the AGA Research Foundation.
1. Park, S.Y., Acosta, A., Camilleri M. et al, Gastric motor dysfunction in patients with functional gastroduodenal symptoms. Am J Gastroenterol. 2017;112:1689-1699.
2. Camilleri, M., McCallum, R.W., Tack, J., Spence, S.C., Gottesdiener, K., Fiedorek, F.T. Efficacy and safety of relamorelin in diabetes with symptoms of gastroparesis: a randomized, placebo-controlled study. Gastroenterology. 2017;153:1240-1250.
3. Pasricha, P.J., Yates, K.P., Sarosiek, I. et al, Aprepitant has mixed effects on nausea and reduces other symptoms in patients with gastroparesis and related disorders. Gastroenterology. 2018;154:65-76.