From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Reglan (metoclopramide) causes agitation as a side effect primarily through its effects on dopamine receptors in the brain, as evidenced by a recent case report of metoclopramide-induced rapid-onset psychosis in a child 1.
Mechanism of Action
Reglan works by blocking dopamine D2 receptors, which helps with gastrointestinal motility but can disrupt normal dopamine signaling in the central nervous system. This disruption can lead to agitation, restlessness, anxiety, and in some cases more severe neurological side effects like akathisia (an intense feeling of inner restlessness) or tardive dyskinesia (involuntary movements).
Risk Factors
These effects are more common at higher doses, with prolonged use (especially beyond 12 weeks), in elderly patients, and in those with kidney or liver impairment. The risk of agitation and other neuropsychiatric effects is why Reglan carries a black box warning and why physicians typically limit its use to short-term therapy when possible.
Clinical Implications
If a patient experiences agitation while taking Reglan, they should contact their healthcare provider immediately, as dose reduction or medication discontinuation may be necessary. A study from 2007 highlights the potential for persistent generalized anxiety after brief exposure to metoclopramide 2, further emphasizing the need for cautious use. In contrast, domperidone, another dopamine-2 receptor antagonist, has minimal penetration through the blood-brain barrier and does not cause adverse neurological symptoms, making it a safer alternative for long-term administration 3. However, the most recent and relevant evidence comes from the 2024 case report, which underscores the importance of careful pharmacological management, especially in children and individuals with neurodevelopmental disorders 1.
Key Points
- Reglan (metoclopramide) can cause agitation and other neuropsychiatric effects due to its dopamine antagonist properties.
- The risk of these effects is higher with prolonged use, higher doses, and in certain patient populations.
- Domperidone is a safer alternative for long-term use due to its minimal penetration through the blood-brain barrier.
- Recent evidence highlights the need for cautious use of Reglan, especially in vulnerable populations 1.