Intravenous Valproate (Depakote) Dosing for Agitation
For agitation management, intravenous valproate (Depakote) should be administered at a dose of 20-30 mg/kg IV at a rate not exceeding 3 mg/kg per minute, with close cardiac monitoring. 1
Dosing Protocol for IV Valproate in Agitation
Initial Dosing
- Loading dose: 20-30 mg/kg IV
- Maximum infusion rate: 3 mg/kg per minute (40 mg/min maximum)
- Monitor heart rate via ECG during administration
Monitoring During Administration
- Reduce infusion rate if heart rate decreases by 10 beats per minute or more
- Monitor vital signs closely throughout administration
- Watch for signs of respiratory depression
- Have airway equipment immediately available
Follow-up Dosing
- If needed for continued agitation, maintenance dosing can be considered at 1-5 mg/kg every 6 hours
- Titrate to clinical effect
Patient Selection Considerations
Valproate IV may be particularly useful in patients who:
- Have had suboptimal responses to conventional therapy (benzodiazepines/antipsychotics)
- Are experiencing concerning side effects from conventional agents 2
- Are NPO (nothing by mouth) but require agitation management 2
- Have cardiac concerns that preclude use of other agents like phenytoin 1
Monitoring Parameters
- Continuous cardiac monitoring during and after administration
- Frequent blood pressure checks
- Continuous pulse oximetry
- Consider arterial line for hemodynamic monitoring in severe cases
Potential Adverse Effects
- Dizziness
- Thrombocytopenia (monitor platelets if continued dosing)
- Liver toxicity (monitor liver enzymes with continued use)
- Hyperammonemia
- Sedation
Clinical Pearls
- IV valproate has shown efficacy in controlling behavioral symptoms of delirium and agitation when conventional therapy is inadequate 2
- Lower infusion rates are associated with fewer adverse effects
- For patients requiring longer-term management, transition to oral valproate can be considered once the acute agitation is controlled
- Relatively low doses of valproate appear to be useful in treating agitation associated with various conditions 3
Cautions
- Limited evidence exists for valproate in agitation specifically compared to its use in seizure management
- The evidence for valproate in agitation is not as robust as for some conventional agents like lorazepam
- For agitation in dementia specifically, evidence is preliminary and inconsistent 4
- Monitor liver function tests and platelets with continued use
While the strongest evidence for IV valproate comes from its use in seizure management, clinical experience and case reports support its use in agitation when conventional therapies are inadequate or contraindicated.