Can metoclopramide (Reglan) with diphenhydramine (Benadryl) be used to reduce tardive dyskinesia?

From the Guidelines

Metoclopramide (Reglan) with diphenhydramine (Benadryl) is not recommended for reducing tardive dyskinesia, as metoclopramide can exacerbate the condition and diphenhydramine may only temporarily mask symptoms. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia, published in 2020 1, emphasizes the importance of evidence-based treatments for managing schizophrenia and its associated symptoms, including tardive dyskinesia.

Key Considerations

• Tardive dyskinesia is a side effect associated with long-term use of antipsychotic medications, including metoclopramide, due to its dopamine-blocking properties.
• The primary management of tardive dyskinesia involves discontinuing the causative agent whenever possible.
• For treatment of existing tardive dyskinesia, FDA-approved medications include valbenazine (Ingrezza) and deutetrabenazine (Austedo), which are vesicular monoamine transporter 2 (VMAT2) inhibitors specifically designed to address tardive dyskinesia symptoms, as recommended by the APA guideline 1.

Treatment Approach

• Discontinuation of the offending agent, in this case, metoclopramide, is the first step in managing tardive dyskinesia.
• Evaluation by a neurologist or psychiatrist is crucial for proper diagnosis and management of tardive dyskinesia.
• Treatment with VMAT2 inhibitors, such as valbenazine or deutetrabenazine, should be considered under the guidance of a specialist.

Important Notes

• Diphenhydramine may temporarily alleviate some symptoms but does not address the underlying cause of tardive dyskinesia and could potentially worsen symptoms long-term due to its anticholinergic effects.
• The APA guideline suggests that patients with moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) 1.

From the Research

Tardive Dyskinesia and Metoclopramide (Reglan) with Diphenhydramine (Benadryl)

• The use of metoclopramide (Reglan) has been associated with the development of tardive dyskinesia, a hyperkinetic movement disorder caused by the use of dopamine receptor-blocking agents 2, 3, 4.
• Diphenhydramine (Benadryl) is an antihistamine that can also have anticholinergic effects, but there is no direct evidence to suggest that it can reduce tardive dyskinesia when used with metoclopramide.
• Metoclopramide is a dopamine receptor antagonist, and its use can lead to the development of tardive dyskinesia, especially in high-risk groups such as elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy 3, 4.
• The risk of tardive dyskinesia from metoclopramide use is estimated to be low, in the range of 0.1% per 1000 patient years, which is far below the previously estimated 1%-10% risk suggested in treatment guidelines 3.
• There is no evidence to suggest that the combination of metoclopramide and diphenhydramine can reduce the risk of tardive dyskinesia, and the use of metoclopramide should be carefully considered and monitored, especially in high-risk patients 2, 3, 4, 5, 6.

Key Points to Consider

• Metoclopramide can cause tardive dyskinesia, especially in high-risk groups.
• The risk of tardive dyskinesia from metoclopramide use is estimated to be low.
• There is no evidence to suggest that diphenhydramine can reduce the risk of tardive dyskinesia when used with metoclopramide.
• The use of metoclopramide should be carefully considered and monitored, especially in high-risk patients.