Is Benadryl (diphenhydramine) or benzodiazepines better to give with Reglan (metoclopramide) for an acute dystonic reaction?

Management of Acute Dystonic Reactions from Reglan (Metoclopramide)

Diphenhydramine (Benadryl) is the preferred first-line treatment for acute dystonic reactions caused by metoclopramide (Reglan), with benzodiazepines serving as an alternative when diphenhydramine is contraindicated or ineffective. 1, 2

First-Line Treatment: Diphenhydramine

The FDA-approved metoclopramide label specifically recommends diphenhydramine as the first-line treatment for acute dystonic reactions:

• Dosing: 50 mg diphenhydramine intramuscularly 1
• Onset: Symptoms usually subside promptly after administration
• Mechanism: Diphenhydramine's antihistamine properties may contribute to its antidystonic effects 3

The American Academy of Pediatrics also supports this approach, listing diphenhydramine at a dose of 1-2 mg/kg (maximum initial dosage: 50 mg) for dystonic reactions 2.

Alternative Treatment: Benzodiazepines

Benzodiazepines can be used as an alternative treatment when:

• Diphenhydramine is contraindicated
• Patient has not responded adequately to diphenhydramine
• Additional sedation is required

Options include:

• Diazepam: 5 mg IV/IM 4
• Lorazepam: Can be used in combination with antipsychotics for agitation with dystonia 2

Treatment Algorithm

1. First-line: Diphenhydramine 50 mg IM (adults) or 1-2 mg/kg (children)
2. If no response within 15-20 minutes: Consider repeating diphenhydramine dose or switching to benzodiazepine
3. Alternative: Benztropine mesylate 1-2 mg IM can also be used 1
4. For severe cases: Consider combination therapy with both diphenhydramine and benzodiazepine

Clinical Considerations

Presentation of Metoclopramide-Induced Dystonia

• Involuntary movements of limbs and facial grimacing
• Torticollis
• Oculogyric crisis
• Rhythmic tongue protrusion
• Trismus
• Laryngospasm (rare but potentially life-threatening) 1

Risk Factors for Metoclopramide-Induced Dystonia

• Typically occurs within first 24-48 hours of treatment
• Higher incidence in:
  • Pediatric patients
  • Adults under 30 years of age
  • Higher doses (as used in chemotherapy-induced nausea) 1
  • Incidence approximately 1 in 500 patients at standard adult dosages 1

Important Cautions

1. Paradoxical reactions: Diphenhydramine can rarely cause paradoxical excitement or agitation 2

2. Respiratory monitoring: Both diphenhydramine and benzodiazepines can cause sedation and respiratory depression, especially when used together 2

3. Benzodiazepine considerations:

   • May cause paradoxical behavioral disinhibition, especially in younger children and those with developmental disabilities 2
   • Diazepam should be administered over ~2 minutes to avoid pain at IV site 2

4. Discontinuation of metoclopramide: Consider stopping or reducing the dose of metoclopramide after treating the acute dystonic reaction to prevent recurrence 1

Comparative Efficacy

While both medications are effective, some evidence suggests that anticholinergic agents like benztropine may result in faster recovery times than diphenhydramine in treating drug-induced dystonic reactions 5. However, the FDA label specifically recommends diphenhydramine as first-line therapy 1, making it the preferred initial treatment.

Despite the rare possibility that diphenhydramine itself could induce dystonia in some patients 4, its established efficacy and safety profile in treating metoclopramide-induced dystonia make it the treatment of choice.