What is the role of Depakote (valproate) in treating agitated delirium?

Valproic Acid (Depakote) for Agitated Delirium

Valproic acid (Depakote) is not recommended as a first-line treatment for agitated delirium, but may be considered in specific cases where conventional therapies have failed or are contraindicated.

First-Line Management Approach for Agitated Delirium

Non-pharmacological Interventions

• Multicomponent, non-pharmacological interventions should be implemented first for all patients with delirium 1
• These interventions include:
  • Reorientation and cognitive stimulation 1
  • Use of clocks and calendars 1
  • Optimizing sleep by minimizing light and noise 1
  • Reducing sedation when possible 1
  • Early mobilization and rehabilitation 1
  • Ensuring patients have access to hearing aids and glasses if needed 1

Pharmacological Management

• Antipsychotics are not recommended for routine use in delirium treatment 1
• Short-term use of antipsychotics may be warranted in patients experiencing:
  • Significant distress from hallucinations or delusions 1
  • Severe agitation that poses risk to self or others 1
• For mechanically ventilated patients where agitation is preventing weaning/extubation, dexmedetomidine is recommended 1

Role of Valproic Acid (Depakote) in Agitated Delirium

Current Evidence

• Limited evidence exists for valproic acid in delirium management 2
• No randomized controlled trials have evaluated valproic acid specifically for delirium 2
• Most studies are retrospective, case series, or case reports 2

Potential Benefits

• May improve agitation without causing QTc prolongation, excessive sedation, or parkinsonism 3
• In small retrospective studies, valproic acid has shown:
  • Downward trends in prevalence of agitation (47.8% to 16.7%) 4
  • Reduction in delirium (84.8% to 63.3%) 4
  • Decreased need for other medications (dexmedetomidine, benzodiazepines, antipsychotics) 4
• Has been used successfully as monotherapy in some palliative care patients 3

Potential Risks and Monitoring

• Common side effects include hyperammonemia (12-19%) and thrombocytopenia (9-13%) 2
• May itself induce delirium, particularly in elderly patients with dementia 5
• Requires monitoring of:
  • Complete blood count (platelets) 2
  • Liver function tests 2
  • Ammonia levels when clinically indicated 2

Practical Considerations for Valproic Acid Use

Dosing

• Typical starting dose: approximately 500-800 mg/day 3, 2
• Mean dose in studies: 733 mg/day initially, increasing to 1061 mg/day 2
• Available in multiple formulations:
  • Intravenous (Depacon) for NPO patients 6
  • Liquid oral preparation (Depakene) for administration via nasogastric tube 6
  • Oral tablets/capsules 2

Patient Selection

• Consider in patients with:
  • Suboptimal response to conventional therapy 6
  • Concerning side effects from antipsychotics or benzodiazepines 6
  • Contraindications to antipsychotics (e.g., prolonged QTc) 3
• May be particularly useful in palliative care settings 3

Clinical Algorithm for Agitated Delirium Management

1. Implement multicomponent non-pharmacological interventions for all patients 1
2. Identify and treat reversible causes of delirium 1
3. For pharmacological management:
   • If patient has distressing hallucinations/delusions or severe agitation: Consider short-term haloperidol or atypical antipsychotic 1
   • If patient is mechanically ventilated with agitation preventing extubation: Consider dexmedetomidine 1
   • If conventional therapy is inadequate or contraindicated: Consider valproic acid 3, 6
4. If valproic acid is used:
   • Start at 500-800 mg/day 3, 2
   • Monitor for efficacy and side effects 2
   • Discontinue if delirium worsens or side effects occur 5

Important Caveats

• Discontinue antipsychotics immediately following resolution of distressing symptoms 1
• Benzodiazepines should not be used as initial treatment for delirium unless treating alcohol or benzodiazepine withdrawal 1
• Valproic acid should be considered a second or third-line agent given the limited high-quality evidence 2
• All pharmacological interventions should be used for the shortest duration possible 1