Normal Therapeutic Range for Depakote (Valproate)
The normal therapeutic range for Depakote (valproate) is 50-100 μg/mL (or 50-100 mg/L) for most clinical applications. 1
Therapeutic Ranges by Indication
The therapeutic range of valproate varies slightly depending on the condition being treated:
- Epilepsy/Seizure Disorders: 50-100 μg/mL 1
- Bipolar Disorder: 40-90 μg/mL 2
- Status Epilepticus: Higher levels may be targeted in acute settings
Monitoring Recommendations
When to Check Levels
- Initial therapy: Check levels after reaching steady state (approximately 2-4 days)
- Dose adjustments: 2-3 days after changing dose
- Maintenance therapy: Every 3-6 months 2
- Suspected toxicity: Immediately check levels if toxicity is suspected
Timing of Blood Draws
- Trough levels (just before next dose) are most reliable for monitoring
- Samples drawn 2 hours post-dose can help assess peak levels when absorption issues are suspected 3
Dosing Considerations
Initial Dosing
- Start at 10-15 mg/kg/day (or 125-250 mg/day in adults) 2, 1
- Titrate by 5-10 mg/kg/week to achieve clinical response 1
- Maximum recommended dose is typically 60 mg/kg/day 1
Special Populations
- Elderly: Lower starting doses and slower titration due to decreased clearance 1
- Patients on enzyme-inducing medications: May require higher doses
Toxicity Concerns
Concentration-Related Adverse Effects
- >110 μg/mL in females: Significantly increased risk of thrombocytopenia 1
- >135 μg/mL in males: Significantly increased risk of thrombocytopenia 1
- >1000 μg/mL: Severe toxicity requiring immediate intervention, potentially including hemodialysis 4
Common Adverse Effects
- Gastrointestinal disturbances
- Tremor
- Hair loss
- Weight gain
- Sedation
- Thrombocytopenia (dose-dependent) 2
Clinical Pearls
- The correlation between serum levels and clinical effect is not always perfect - some patients may respond at lower levels while others require higher levels
- Protein binding of valproate is nonlinear, meaning free (unbound) drug levels increase disproportionately at higher total concentrations
- Drug interactions can significantly affect valproate levels, particularly with other anticonvulsants like lamotrigine 5
- Valproate has a relatively narrow therapeutic window, making regular monitoring important for both efficacy and safety
Remember that while the therapeutic range provides a useful guideline, clinical response and tolerability should always be considered when evaluating the appropriateness of a patient's valproate level.