Depakote Starting Dose for Adults
For mood stabilization in bipolar disorder, start with 125 mg twice daily (total 250 mg/day) and titrate upward to achieve therapeutic blood levels of 40-90 mcg/mL, while for seizure disorders, start with 10-15 mg/kg/day and increase by 5-10 mg/kg/week to achieve therapeutic levels of 50-100 mcg/mL. 1, 2, 3
Indication-Specific Dosing
Bipolar Disorder/Mood Stabilization
- Begin with 125 mg twice daily (250 mg total daily dose) as recommended by the American Academy of Family Physicians 1, 2
- Titrate gradually upward to achieve therapeutic blood levels of 40-90 mcg/mL 1, 2
- Lower doses (125-500 mg/day) may be sufficient for milder bipolar spectrum disorders like cyclothymia, with mean effective doses around 351 mg/day corresponding to serum levels of 32.5 mcg/mL 4
- For acute mania requiring rapid control, an oral loading strategy of 30 mg/kg/day for 2 days followed by 20 mg/kg/day is well-tolerated and achieves therapeutic levels (56-124 mcg/mL) within 3 days 5
Seizure Disorders (Complex Partial or Absence Seizures)
- Start at 10-15 mg/kg/day for monotherapy or adjunctive therapy 3
- Increase by 5-10 mg/kg/week until optimal clinical response is achieved 3
- Target therapeutic range is 50-100 mcg/mL for seizure control 1, 3
- Optimal response typically occurs at daily doses below 60 mg/kg/day 3
- For absence seizures specifically, the FDA label recommends starting at 15 mg/kg/day with weekly increases of 5-10 mg/kg/day, up to a maximum of 60 mg/kg/day 3
Status Epilepticus (Emergency Setting)
- Administer IV loading dose of 20-30 mg/kg at an infusion rate up to 6-10 mg/kg/min 1, 6
- This achieves 63-88% efficacy in controlling seizures within 20 minutes 1, 6
- This is superior to phenytoin (66% vs 42% efficacy) with fewer adverse effects 1
Formulation Considerations
Dosing Frequency
- If total daily dose exceeds 250 mg, divide into multiple doses 3
- Extended-release formulation (divalproex-ER) can be dosed once daily across a wide dose range 7
- Standard enteric-coated divalproex should NOT be dosed once daily at high doses (≥2000 mg/day) due to risk of excessive peak concentrations (>125 mg/L) and potential toxicity 7
Monitoring Requirements
Initial Monitoring
- Check valproate levels to confirm therapeutic range: 40-90 mcg/mL for mood stabilization or 50-100 mcg/mL for seizures 1, 2
- Monitor liver enzymes, complete blood count (especially platelets), and coagulation parameters (PT/PTT) as indicated 1, 2
- For acute mania, serum levels of 45-100 mcg/mL are associated with optimal efficacy and tolerability 8
Ongoing Monitoring
- Once stable, check levels every 3-6 months 1
- Continue monitoring liver enzymes, platelets, and coagulation parameters periodically 2
Critical Safety Considerations
Dose-Related Toxicity
- Thrombocytopenia risk increases significantly at trough levels above 110 mcg/mL in females and 135 mcg/mL in males 3
- Adverse effects are disproportionately associated with serum levels ≥125 mcg/mL 8
- No safety data exists for doses above 60 mg/kg/day 3