Medications are used to try to help reduce symptoms of gastroparesis. The drug categories commonly used are prokinetic (promotility) agents and antiemetic agents.
There is a lack of evidence-based information about what drugs work best for patients with gastroparesis. Drugs are often prescribed off-label by doctors, based on their clinical experience and how the drugs treat similar symptoms in other conditions. Only one drug, metoclopramide, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of gastroparesis.
Off-label use is the permissible practice by doctors to prescribe medications for other than their FDA approved intended indications.
Prokinetic, or promotility, agents directly help the stomach empty more quickly and may improve symptoms such as nausea, vomiting, and bloating.
Metoclopramide, a dopamine antagonist, has been available since 1983. It is the only FDA approved medication that improves stomach emptying. Multiple clinical trials show that it improves symptoms in about 40% of patients. Intolerable side effects are common and 20–40% of patients cannot take this drug.
The most bothersome side effect, tardive dyskinesia, is a rare but serious movement disorder that is often irreversible. The risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose. Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia. (More information at this FDA page)
Domperidone, a peripheral dopamine antagonist, is a prokinetic agent that has never been approved by the FDA. It is similar in effectiveness to metoclopramide, but has fewer side effects. In the U.S. it can be obtained through a doctor under special arrangements and is available in Canada, Mexico, New Zealand, Japan, and Europe. An intravenous form of domperidone was removed from the market in 1980 because of some unexpected serious heart problems (cardiac arrhythmias). An electrocardiogram (EKG), which tests electrical activity in the heart, should be done before starting this medication. Follow-up EKG is recommended in those who are taking the drug. Caution should be used in older patients or those with known cardiac disease.
Erythromycin is an antibiotic that is structurally similar to motilin, a hormone that speeds up stomach emptying. Motilin is decreased in people with diabetes. About 40% of people with diabetic gastroparesis will improve with short courses of erythromycin. However, effectiveness of erythromycin often decreases sharply after several weeks of taking the drug. Possible side effects of erythromycin include nausea, vomiting, and abdominal cramps.
Antiemetic agents are used to treat nausea and vomiting, which are disabling symptoms. These agents do not improve gastric emptying.
These drugs work on a range of receptors in the nervous system in the body. There are a number of these medications, which have been developed for other conditions. For gastroparesis, doctors will make recommendations based on clinical experiences and observations, and individual patient needs. Among these drugs are certain serotonin 5-HT3 receptor antagonists, antihistamines, phenothiazines, low-dose tricyclic antidepressants, and others.
Many of these drugs come in multiple formulations so that they can be taken as an oral tablet, dissolvable tablet, liquid, or intravenously (IV) as required. Possible side effects for each of these drugs should be discussed by the doctor and patient.
Botulinum toxin (Botox) is a nerve blocking agent. Some initial research studies in small numbers of patients showed modest improvement in gastroparesis symptoms and the rate of gastric emptying following the injections of Botox into the pylorus, the opening from the stomach into the small intestine. However, other more well-designed studies have shown no improvement in symptoms compared to placebo. It is not a generally recommended treatment for gastroparesis, based on randomized controlled trials.
Adapted from IFFGD Publication #556 by J. Patrick Waring, MD, Digestive Healthcare of Georgia, Atlanta, GA; and William F. Norton, Communications Director, International Foundation for Functional Gastrointestinal Disorders, Milwaukee, WI.