Indications for Depakote (Valproate)
Depakote (valproate) is FDA-approved for complex partial seizures, simple and complex absence seizures, and multiple seizure types that include absence seizures, as well as for the treatment of bipolar disorder, particularly manic or mixed episodes. 1
Neurological Indications
Seizure Disorders
- Monotherapy and adjunctive therapy for complex partial seizures in adults and children 10 years and older 1
- Sole and adjunctive therapy for simple and complex absence seizures 1
- Adjunctive therapy in patients with multiple seizure types that include absence seizures 1
- Refractory status epilepticus - IV valproate has been shown to be at least as effective as phenytoin with potentially fewer adverse effects 2
Dosing for Seizure Disorders
- Initial dose: 10-15 mg/kg/day
- Titration: Increase by 5-10 mg/kg/week to achieve optimal clinical response
- Target dose: Usually below 60 mg/kg/day
- Therapeutic plasma level: 50-100 μg/mL
- Risk of thrombocytopenia increases at plasma concentrations above 110 μg/mL in females and 135 μg/mL in males 1
Psychiatric Indications
Bipolar Disorder
- Treatment of manic or mixed episodes in bipolar I disorder 3
- Maintenance treatment of bipolar disorder - should continue for at least 2 years after the last episode 2
- Bipolar depression - may be used as monotherapy or in combination with other agents 4
Other Psychiatric Applications
- Impulsive aggression
- Post-traumatic stress disorder 3
Monitoring Requirements
Laboratory Monitoring
- Baseline liver function tests, complete blood counts, and pregnancy tests (in females) 2
- Periodic monitoring (every 3-6 months) of:
- Serum drug levels
- Hepatic function
- Hematological indices 2
Clinical Monitoring
- Weight and body mass index (BMI)
- Signs of potential adverse effects:
- Gastrointestinal disturbances
- Tremor
- Hair loss
- Drowsiness
- Weight gain 5
Important Considerations and Contraindications
Safety Concerns
- Fatal hepatic dysfunction risk - especially in children under 2 years of age receiving polytherapy (risk as high as 1 in 600-800 in high-risk groups) 5
- Teratogenicity - 1-3% risk of neural tube defects; should be avoided in pregnant patients 6, 5
- Polycystic ovary syndrome - may be more common in women treated with valproate 5
- Pancreatitis - rare but serious adverse effect 5
Adverse Effects
- Common: Tremor, weight gain, gastrointestinal disturbances, liver dysfunction, metabolic acidosis, thrombocytopenia 7
- Hair-related: Diffuse, non-scarring, dose-related hair loss; changes in texture, curling, graying 7
Special Populations
Children and Adolescents
- Careful monitoring required in children with bipolar disorder
- Psychoeducation should be routinely offered to individuals and their families 2
- Diagnostic status should be reviewed over time to ensure that medication therapy is justified 2
Elderly and Patients with Organ Impairment
- Lower doses and slower titration recommended for elderly patients
- Dose adjustments may be required for patients with renal or hepatic impairment 6
Extended-Release Formulation
- Improved tolerability and convenience with once-daily dosing
- Potential to improve patient compliance and clinical outcomes 3
Valproate remains one of the most widely prescribed antiepileptic drugs worldwide and has broad therapeutic applications across both neurological and psychiatric conditions. However, its use requires careful consideration of potential adverse effects and appropriate monitoring to ensure safe and effective treatment.