Depakote Starting Dose
For mood stabilization in bipolar disorder, start Depakote at 125 mg twice daily (250 mg/day total) and titrate upward to achieve therapeutic blood levels of 40-90 mcg/mL. 1
Dosing by Clinical Indication
Bipolar Disorder/Mood Stabilization
- Initial dose: 125 mg twice daily as recommended by the American Academy of Family Physicians 1
- Titrate gradually to therapeutic blood level (40-90 mcg/mL) 1, 2
- For milder bipolar spectrum disorders (cyclothymia, bipolar II), doses as low as 125-500 mg/day (mean 351 mg/day) with blood levels around 32.5 mcg/mL may be sufficient 3
- More severe bipolar disorders typically require higher doses to achieve blood levels in the 50-100 mcg/mL range 3
Acute Mania (Rapid Loading)
- Loading dose: 20-30 mg/kg/day orally for rapid control 4, 5
- This achieves therapeutic serum concentrations (≥50 mcg/mL) within 2-3 days 4
- One well-tolerated strategy: 30 mg/kg/day for 2 days, then 20 mg/kg/day thereafter, producing levels of 56-124 mcg/mL within 3 days 5
- Response typically occurs within 1-4 days of achieving therapeutic levels 4
- This approach is safe even with concurrent psychotropic medications 4, 5
Seizure Disorders (Oral Maintenance)
- Complex partial seizures: 10-15 mg/kg/day initially 6
- Increase by 5-10 mg/kg/week to achieve optimal response 6
- Optimal clinical response usually achieved at doses below 60 mg/kg/day 6
- Target therapeutic range: 50-100 mcg/mL 6
- Simple/complex absence seizures: 15 mg/kg/day initially, increasing weekly by 5-10 mg/kg/day 6
- Maximum recommended dose: 60 mg/kg/day 6
Status Epilepticus (IV Loading)
- Loading dose: 20-30 mg/kg IV for acute seizure control 7
- Infusion rate: up to 6-10 mg/kg/min is safe and well-tolerated 7
- This produces efficacy in 63-88% of patients with status epilepticus 7, 1
- Initial concentrations may reach 65-80 mcg/mL or higher, which is acceptable in this acute setting 2
- Superior to phenytoin for convulsive status epilepticus (66% vs 42% efficacy) with fewer adverse effects 7
Dosing Administration Details
- Divide doses exceeding 250 mg/day to improve tolerability 6
- When converting from adjunctive to monotherapy, reduce concomitant antiepileptic drugs by approximately 25% every 2 weeks 6
- For adjunctive therapy in seizures, add valproate at 10-15 mg/kg/day and increase by 5-10 mg/kg/week 6
Monitoring Requirements
- Check valproate levels to confirm therapeutic range (40-90 mcg/mL for mood stabilization; 50-100 mcg/mL for seizures) 1, 2, 6
- Monitor liver enzymes, complete blood count (especially platelets), and coagulation parameters as indicated 1, 2
- Once stable, check levels every 3-6 months per the American Academy of Child and Adolescent Psychiatry 2
Critical Safety Considerations
- Thrombocytopenia risk increases significantly at trough levels above 110 mcg/mL in females and 135 mcg/mL in males 6
- Common side effects with higher doses include weight gain (20% with >5.5 kg gain), tremor (45%), and hair changes (12%) 8
- Loading strategies are generally well-tolerated with minimal side effects when properly monitored 4, 5