Depakote (Valproate) Dosing
For mood stabilization and agitation control, start with 125 mg twice daily and titrate to a therapeutic blood level of 40-90 μg/mL, while for epilepsy, begin with 10-15 mg/kg/day (typically 500-750 mg/day in divided doses) and increase by 5-10 mg/kg/week to achieve optimal seizure control, with most patients responding at doses below 60 mg/kg/day. 1, 2, 3
Initial Dosing by Indication
Mood Stabilization and Agitation
- Start at 125 mg twice daily for behavioral control in conditions like Alzheimer's disease or bipolar disorder 1, 2
- Titrate gradually to achieve therapeutic blood levels of 40-90 μg/mL 1, 2
- This lower starting dose minimizes gastrointestinal side effects and allows for tolerability assessment 3
Epilepsy (Complex Partial and Absence Seizures)
- Initial dose: 10-15 mg/kg/day (typically 500-750 mg/day for average adults) 3
- Increase by 5-10 mg/kg/week until seizures are controlled or side effects emerge 3
- Target therapeutic range: 50-100 μg/mL for most seizure types 3
- Maximum recommended dose: 60 mg/kg/day (typically 3000-4500 mg/day in adults) 3
- Doses exceeding 250 mg/day should be divided into 2-3 doses to minimize GI irritation 3
Status Epilepticus (Emergency)
- Loading dose: 20-30 mg/kg IV over 10 minutes 2, 4
- May repeat with an additional 20 mg/kg after 15 minutes if seizures persist (maximum total 40 mg/kg) 4
- Efficacy rate of 63-88% for status epilepticus 2, 4
Dosing by Weight (For Initial 15 mg/kg/day)
| Weight | Total Daily Dose |
|---|---|
| 10-24.9 kg (22-55 lbs) | 250 mg |
| 25-39.9 kg (55-88 lbs) | 500 mg |
| 40-59.9 kg (88-132 lbs) | 750 mg |
| 60-74.9 kg (132-165 lbs) | 1000 mg |
| 75-89.9 kg (165-198 lbs) | 1250 mg |
Formulation-Specific Considerations
Extended-Release (Depakote ER)
- Can be dosed once daily across the entire dose range 5
- Maintains therapeutic levels for 24 hours with minimal peak-trough fluctuation 5
- Preferred for doses ≥2000 mg/day to avoid toxicity risk 5
Delayed-Release (Standard Depakote)
- Requires twice-daily or three-times-daily dosing for doses >1125 mg/day 5
- Once-daily dosing at high doses (≥2000 mg) produces dangerous peak concentrations >125 mg/L 5
- Should NOT be used once-daily at high total daily doses due to toxicity risk 5
Critical Monitoring Requirements
Check these parameters regularly to prevent serious adverse events:
- Liver enzymes at baseline and regularly throughout treatment 1, 2, 3
- Complete blood count, especially platelets (thrombocytopenia risk increases significantly at levels >110 μg/mL in females, >135 μg/mL in males) 2, 3
- Prothrombin time and partial thromboplastin time as indicated 1, 2
- Serum valproate level within 48-72 hours after loading dose or major dose changes 4
Special Population Adjustments
Elderly Patients
- Start at lower doses due to decreased unbound clearance and increased somnolence risk 3
- Increase more slowly with regular monitoring for dehydration, decreased food/fluid intake, and excessive somnolence 3
- Consider dose reduction or discontinuation if patient shows decreased oral intake or excessive sedation 3
Patients on Enzyme-Inducing Drugs
- Phenytoin, carbamazepine, and phenobarbital reduce valproate half-life from 9-18 hours to 5-12 hours 6
- May require higher doses or more frequent dosing to maintain therapeutic levels 6
- Valproate can increase phenobarbital and lamotrigine levels, requiring dose adjustments of these agents 6
Common Pitfalls to Avoid
- Do NOT use once-daily standard Depakote at doses ≥2000 mg/day - this creates dangerous peak concentrations and increases toxicity risk 5
- Do NOT abruptly discontinue in patients with seizure disorders due to risk of precipitating status epilepticus 3
- Avoid doses producing levels >110 μg/mL (females) or >135 μg/mL (males) as thrombocytopenia risk increases significantly 3
- Monitor for weight gain (occurs in 20% of patients), tremor (45%), and hair changes (12%) as dose-related adverse effects 6, 7