Non-dose-related side effects of valproate

The clinical and histological findings in 88 patients in whom hepatotoxicity with valproate has been reported were reviewed. The characteristic lesion is microvesicular steatosis. Hepatotoxicity appears to be an idiosyncratic reaction and is most likely to appear within 6 months from the start of therapy, especially in young patients on comedication. The condition may be reversible if the drug is immediately withdrawn in patients who show acute gastrointestinal symptoms, drowsiness or lethargy, jaundice, or change in seizure pattern. Clinical monitoring is more important than laboratory monitoring. The outcome of pregnancies in 344 women who received valproate in the first trimester was reviewed. There were 225 normal babies and 68 abnormal babies. The role of valproate in the aetiology of neural tube defects remains uncertain, but mothers treated with valproate should receive prenatal counselling.