When first-line pharmacologic prokinetic treatment for gastroparesis does not adequately reduce cardinal symptoms within the expected assessment window, a structured next-line approach is indicated.

Previous Line — Failure Condition

First-line pharmacologic prokinetic therapy — metoclopramide or erythromycin — did not achieve a sufficient reduction in nausea, vomiting, early satiety, and postprandial fullness at the 4–8 week assessment point.

Next Step — Second-Line Approach

After prokinetic failure, second-line pharmacologic agents may be considered. Agent selection is made through shared decision-making based on the individual patient’s profile. The specific options and how to choose among them are detailed in the full structured protocol.

References

DOI: 10.1053/j.gastro.2025.08.004

In individuals with gastroparesis, the AGA suggests against use of domperidone as a first-line treatment.
In individuals with gastroparesis, the AGA suggests against the use of prucalopride as a first-line treatment.
In individuals with gastroparesis, the AGA suggests against the use of aprepitant as a first-line treatment.
In patients with gastroparesis, the AGA suggests against the use of nortriptyline as a first-line treatment.
Clinical experience of the content experts on the panel suggests that tricyclic antidepressants should be started at low doses (10–25 mg), given at night to help avoid adverse effects, and increased slowly to maximize effect while minimizing risk of adverse effects.
In patients with gastroparesis, the AGA suggests against the use of buspirone as a first-line treatment.
In individuals with gastroparesis, the AGA suggests against the use of cannabidiol (CBD) except in the context of a clinical trial.
The Guideline Panel Content Experts usually assess the efficacy of domperidone at 4–8 weeks to decide whether the treatment should be continued.

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Gastroparesis When First-Line Prokinetic Therapy Has Not Achieved Symptom Control

References