Valproic acid-induced pancreatitis: 16 new cases and a review of the literature.

BACKGROUND: Acute pancreatitis is rarely seen in children, and, in contrast to cases in adults, it is often drug induced. One possible medication is the antiepileptic drug valproic acid (VPA), which is commonly prescribed for generalized and focal epilepsy, migraine, neuropathic pain, and bipolar disorder. The common side effects associated with VPA are typically benign, but less common but more serious adverse effects may occur. These include hepatotoxicity, hyperammonemic encephalopathy, coagulation disorders, and pancreatitis. Since 1979, a few cases of pancreatitis induced by VPA have been published in the medical literature. METHODS: We mailed a questionnaire to all members of the "German Section of the International League against Epilepsy," asking about VPA-induced side effects. We also reviewed the medical literature for VPA-induced pancreatitis. RESULTS: Fifty-three publications (90 patients) published from 1979 to 2005 were found. Our survey in Germany, however, yielded 16 cases of pancreatitis from 1994 to 2003 whose original files we could study in detail. None of these patients had been published previously. CONCLUSIONS: The difference between 90 patients reported worldwide from 1979 to 2005 and the 16 new documented cases from only Germany over 10 years corroborates that the occurrence of this severe side effect is under reported.

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.