Can Reglan (metoclopramide) be given with Benadryl (diphenhydramine) to reduce the risk of tardive dyskinesia?

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Last updated: June 7, 2025View editorial policy

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From the Research

Benadryl (diphenhydramine) should not be routinely given with Reglan (metoclopramide) to reduce the risk of tardive dyskinesia. While diphenhydramine can help manage acute dystonic reactions from metoclopramide, it does not prevent tardive dyskinesia, which is a separate, potentially irreversible movement disorder that develops with prolonged use of metoclopramide 1. The best way to prevent tardive dyskinesia is to limit metoclopramide use to short durations (less than 12 weeks) and use the lowest effective dose. Metoclopramide carries a black box warning about tardive dyskinesia risk, which increases with total dose and treatment duration. If metoclopramide is needed, it should typically be prescribed at 10 mg up to four times daily, with treatment limited to 5-12 weeks when possible. Patients should be monitored for involuntary movements, and the medication should be discontinued at the first sign of tardive dyskinesia. Elderly patients, especially women, and those with diabetes have higher risk of developing this condition. Alternative medications with lower risk of movement disorders should be considered when appropriate for the patient's condition. Some studies suggest that the risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years 2. However, high-risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the threshold for neurological complications. Valbenazine is a relatively newer option for the treatment of tardive dyskinesia in adults, and it is more selective and has limited toxicities making it an effective treatment regimen 3. It is essential to be aware of the risk of development of tardive dyskinesia even with short-term treatment with metoclopramide and in younger patients 4.

Key considerations for preventing tardive dyskinesia include:

  • Limiting metoclopramide use to short durations (less than 12 weeks)
  • Using the lowest effective dose
  • Monitoring patients for involuntary movements
  • Discontinuing the medication at the first sign of tardive dyskinesia
  • Considering alternative medications with lower risk of movement disorders
  • Being aware of high-risk groups, such as elderly females, diabetics, and patients with liver or kidney failure.

References

Research

Treatment Recommendations for Tardive Dyskinesia.

Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2019

Research

Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited.

Neurogastroenterology and motility, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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