Valproic Acid-Associated Acute Pancreatitis: Systematic Literature Review

Abstract

Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0–24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate.

Valproic acid-induced acute pancreatitis: First case report in Morocco and literature review

“…Bischof and al. [1] showed between 1979 and 2023, among 125 subjects (66% moins de 16 ans predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0-24) months (median and interquartile range) after starting valproic acid.…”

“…However, it is currently believed that valproic acid-associated pancreatic injury result from an accumulation of free radicals secondary to radical scavenger depletion [9,11]. The outcome is favorable in 84% of cases and allows recovery in less than 4 weeks for 81% of cases of pancreatitis [1]. A risk of recurrence after reintroduction of valpraoate is high 84%, hence it would be preferable to change the epilepsy treatment molecule once pancreatitis has appeared under sodium valproate [1].…”

“…The outcome is favorable in 84% of cases and allows recovery in less than 4 weeks for 81% of cases of pancreatitis [1]. A risk of recurrence after reintroduction of valpraoate is high 84%, hence it would be preferable to change the epilepsy treatment molecule once pancreatitis has appeared under sodium valproate [1]. The mortality of valproate acid-related pancreatitis is estimated at 15% [1].…”

“…A risk of recurrence after reintroduction of valpraoate is high 84%, hence it would be preferable to change the epilepsy treatment molecule once pancreatitis has appeared under sodium valproate [1]. The mortality of valproate acid-related pancreatitis is estimated at 15% [1]. Early severity is linked to the onset of a sepsis-like state of shock with risk of multi-organ failure.…”

“…More rarely, several drugs are described as having adverse effects causing acute pancreatitis outside of a context of drug intoxication. Thus, several cases of pancreatitis due to valproic acid are described in the literature, most of which concern children and young adults [1]. We describe a first clinical case in Morocco of an epileptic adolescent treated with sodium valproate who developed severe acute pancreatitis and we review the literature on this subject.…”