Beyond the stomach stall: Current and emerging pharmacotherapeutics for gastroparesis

Abstract

Gastroparesis is a gastrointestinal motility disorder characterized by delayed gastric emptying, which precipitates symptoms like nausea, vomiting, early satiety, and bloating. Diagnosis requires evidence of delayed gastric emptying and exclusion of mechanical obstruction. The Gastroparesis Cardinal Symptom Index measures symptom severity and supports the US Food and Drug Administration (FDA) drug development guidelines. Idiopathic, diabetic, and postsurgical causes are common, with medications such as glucagon-like peptide-1 agonists and opioids also contributing. Symptoms significantly impair quality of life, reduce income, and increase caregiver burden, emergency visits, and hospitalizations. Hence, there is an urgent need to improve or innovate therapeutics for this draining condition. Camilleri and Jencks (2025) provide in Pharmacological Reviews an in-depth discussion of pharmacological treatments for gastroparesis. The authors remind us that as of yet, metoclopramide remains the only FDA-approved drug for gastroparesis treatment, although its usage is limited to 12-week courses because of the rare but serious risk of tardive dyskinesia. Metoclopramide’s mechanism involves central and peripheral dopamine receptor antagonism, providing antiemetic and prokinetic effects. However, its limitations have led to an off-label interest in domperidone, another dopamine antagonist with lower central nervous system penetration, resulting in fewer neurological side effects. Despite similar efficacy to metoclopramide, domperidone is associated with QT prolongation, which requires diligent cardiac monitoring. Domperidone is typically dosed at 10e20 mg 3 times daily and, while effective, is restricted in the United States because of these cardiac risks.