Potential Side Effects of Depakote (Valproate)
Depakote (valproate) can cause numerous side effects ranging from common gastrointestinal disturbances to rare but serious hepatotoxicity and requires careful monitoring, particularly in high-risk populations such as children under 2 years, pregnant women, and those with liver disease. 1
Common Side Effects
Gastrointestinal Effects
- Nausea and vomiting (most common initial side effects)
- Indigestion
- Diarrhea
- Abdominal cramps
- Constipation
- Anorexia or increased appetite 1
Neurological Effects
- Sedation and drowsiness
- Tremor (may be dose-related)
- Dizziness
- Headache
- Ataxia (impaired coordination)
- Diplopia (double vision)
- Confusion
- Paresthesia (abnormal sensations) 1
Dermatological Effects
- Hair loss (alopecia) - diffuse, nonscarring, and dose-related 2
- Changes in hair texture, curling of hair, or graying
- Skin rash
- Photosensitivity
- In rare cases: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis 1
Serious Side Effects
Hepatotoxicity
- Elevated liver enzymes (SGOT, SGPT, LDH)
- Potentially fatal hepatic failure (risk is highest in children under 2 years of age on polytherapy, with incidence of 1 in 600-800 in this group) 3
- Can occur as an idiosyncratic reaction even at therapeutic drug levels 4
Hematologic Effects
- Thrombocytopenia
- Altered bleeding time
- Bruising and petechiae
- Leukopenia
- Pancytopenia (rare)
- Bone marrow suppression 1
Metabolic/Endocrine Effects
- Weight gain
- Hyperammonemia (with or without encephalopathy)
- Polycystic ovary syndrome (PCOS) - particularly in women with epilepsy 5
- Menstrual irregularities, secondary amenorrhea
- Hyperandrogenism 5
- Insulin resistance 5
Pancreatic Effects
- Acute pancreatitis (potentially fatal) 1
Special Population Considerations
Pregnant Women
- Teratogenic effects, including 1-3% risk of neural tube defects 3
- Contraindicated in pregnancy for migraine prevention 1
Elderly Patients
- Increased risk of drowsiness and confusion
- May require lower dosing 1
Children
- Higher risk of hepatotoxicity, especially under 2 years of age
- Requires very careful monitoring 3
Monitoring Recommendations
Baseline Assessment:
- Liver function tests
- Complete blood count with platelets
- Weight measurement
Ongoing Monitoring:
- Regular liver function tests
- Complete blood count
- Ammonia levels if encephalopathy is suspected
- Weight monitoring
- In women: assessment for menstrual irregularities and signs of PCOS 5
Warning Signs Requiring Immediate Attention:
- Jaundice
- Unusual bleeding or bruising
- Severe abdominal pain (possible pancreatitis)
- Significant lethargy or confusion (possible hyperammonemia)
- Severe skin reactions 1
Risk Mitigation
- Use lowest effective dose
- Consider extended-release formulations to minimize fluctuations in serum drug concentrations
- Avoid in patients with liver disease or urea cycle disorders
- Exercise caution when using in women of childbearing potential
- Consider drug interactions (valproate can inhibit metabolism of certain drugs like phenobarbital and lamotrigine) 3
Depakote's side effect profile requires careful consideration of risk-benefit ratio, particularly in high-risk populations, with regular monitoring to detect and manage adverse effects early.