Starting Dose of Depakote (Valproate)
The recommended starting dose of divalproex sodium (Depakote) is 125 mg twice daily (250 mg/day total) when used as a mood stabilizer, with titration to therapeutic blood levels (40-90 mcg/mL). 1
Dosing Guidelines Based on Indication
For Seizure Disorders:
- Initial dose: 10-15 mg/kg/day 2
- Increase by 5-10 mg/kg/week to achieve optimal clinical response
- Optimal response typically achieved at doses below 60 mg/kg/day
- Therapeutic blood level range: 50-100 μg/mL
- If total daily dose exceeds 250 mg, it should be given in divided doses
For Mood Stabilization:
- Initial dose: 125 mg twice daily (250 mg/day total) 1
- Titrate to therapeutic blood level of 40-90 mcg/mL
- Generally better tolerated than other mood stabilizers
For Cyclothymia or Milder Bipolar Disorders:
- Lower doses may be effective (125-500 mg/day, mean 351 mg) 3
- Lower blood levels (mean 32.5 μg/mL) may be sufficient for milder conditions
Special Populations
Elderly Patients:
- Start with reduced dose due to decreased clearance and potentially greater sensitivity to side effects 2
- Increase dose more slowly with regular monitoring
- Monitor for fluid/nutritional intake, dehydration, and somnolence
Children and Adolescents:
- For bipolar disorder: Initial dose of 15 mg/kg/day (not to exceed 750 mg/day) 4
- May increase to maximum of 35 mg/kg/day as needed
Monitoring Requirements
- Liver function tests - monitor regularly
- Complete blood count - monitor platelets
- Coagulation parameters - monitor prothrombin time and partial thromboplastin time as indicated
Important Considerations
- Weight-based dosing is particularly important for seizure disorders
- For adults, if total daily dose exceeds 250 mg, divide into multiple doses
- Extended-release formulation is more appropriate for once-daily dosing, especially at higher doses 5
- Regular enteric-coated formulation should not be dosed once-daily at high doses due to risk of toxicity
Pitfalls to Avoid
- Starting too high - can lead to unnecessary side effects
- Inadequate monitoring - blood levels should be checked to ensure therapeutic range
- Once-daily dosing with regular formulation - can lead to excessive peak concentrations and increased side effects
- Failure to adjust dose in elderly - they require lower starting doses and slower titration
- Not considering drug interactions - valproate may interact with other antiepileptic drugs and medications
Starting with a lower dose and gradually titrating upward based on clinical response and blood levels helps minimize side effects while achieving therapeutic benefit.