Encephalopathy and Hyperammonemia Associated with Valproic Acid

Abstract

Objective:

To discuss the case of a patient who experienced an altered level of consciousness secondary to hyperammonemia associated with valproic acid who had normal drug concentrations and liver function tests.

Case Summary:

A 48-year-old man with a history of seizure disorder treated with valproic acid presented with an altered level of consciousness. An extensive workup revealed only an increased ammonia level. His medications were withheld. Within 24 hours, the ammonia level returned to normal and he was able to be aroused. His antiseizure medication was changed to gabapentin. All of his chronic medications, other than valproic acid, were restarted. The patient has had no further increases in ammonia levels or episodes of altered mental status.

Discussion:

Encephalopathy due to hyperammonemia is generally due to severe liver dysfunction. In our case, however, hyperammonemia occurred in a patient with normal liver function who was also taking valproic acid. An objective causality assessment revealed that the adverse drug event was probably related to valproic acid. A review of the literature indicates that the increased ammonia levels were probably secondary to the effect of valproic acid on the kidneys or the liver. Withdrawal of the offending agent resulted in normalization of ammonia levels and resolution of encephalopathy.

Conclusions:

With a widening of its clinical indications, the use of valproic acid has been increasing. Even though valproic acid concentrations may be therapeutic/nontoxic and liver function tests normal, practitioners are encouraged to check the ammonia level. Hyperammonemia, once recognized, is easily treated.