Valproic acid–induced hyperammonemia: Incidence, clinical significance, and treatment management

Abstract

Introduction:Valproic acid (VPA)–induced hyperammonemia poses several clinical challenges in psychiatric medicine. The reported incidence of this adverse effect varies widely across the literature. Furthermore, practitioners treat hyperammonemia in asymptomatic patients although studies suggest this practice is unnecessary. The purpose of this study is to evaluate if patients with VPA-induced hyperammonemia are appropriately identified for treatment based on their symptom presentation as well as determine the most efficacious treatment approach for VPA-induced hyperammonemia.Methods:This study was completed at a community teaching hospital, and patients were retrospectively identified from June 1, 2011, to June 30, 2016, and included if they were admitted to a psychiatric unit, received at least 1 dose of VPA, and had at least 1 ammonia level drawn during admission. Hyperammonemia was defined as greater than 47 μmol/L, and symptomatic hyperammonemia was defined based on specific symptom presentation. The treatment modality was successful if the ammonia level was within normal range at discharge.Results:Of the 357 patients screened, 347 patients met all inclusion criteria for analysis. The reported incidence of hyperammonemia was found to be 36% with 43.2% of those patients presenting with symptoms. Lactulose initiation was the most common treatment modality chosen (48.7%). Discontinuation of VPA was the most effective treatment (56.3% success rate).Discussion:The results demonstrate that many patients with elevated ammonia levels are asymptomatic and therefore, based on findings within the literature, may not require treatment. Although lactulose was found to be the most common treatment initiated, the most effective was discontinuation of VPA.

Valproic Acid-Induced Hyperammonemic Encephalopathy in a Patient with Bipolar Disorder: A Case Report

“…In most patients, VPA-induced hyperammonemia does not cause encephalopathy; patients are usually asymptomatic and have normal liver function test results. In a study by Baddour et al [13], elevated ammonia levels were not significantly associated with clinical symptoms. In addition, more clinical symptoms were noted in patients with normal ammonia levels.…”

Chronic Valproic Acid Administration Increases Plasma, Liver, and Brain Ammonia Concentration and Suppresses Glutamine Synthetase Activity

“…A review of 24 studies reported that the prevalence of VPA-associated hyperammonemia ranged between 70% and 100% in prospective studies and between 16% and 100% in cross-sectional studies [ 6 ]. One retrospective chart review for 347 patients admitted to a psychiatric unit reported the incidence of VPA-hyperammonemia is about 36%, with 43.2% of those patients with VPA-induced hyperammonemia presenting with symptoms [ 7 ]. This incidence is very close to the 27.8% incidence reported in 158 patients with epilepsy [ 8 ].…”

Noncirrhotic hyperammonemia: A factor behind dementia to alter mental status

“…Patients with delirium may present with inattention, agitation, aggressive behavior or thinking, and disorganized speech, which were the patient's symptoms in this case. It has been reported that valproic acid may induce delirium due to hyperammonemia . In our case, the patient was given Haldol to control delirium and lactulose to reduce serum ammonia.…”

“…In adults, the secondary hyperammonemia is more common, especially in the presence of hepatic disorders. It may also happen with normal hepatic function when mitochondrial pathways are interrupted by Reye's syndrome or medications, such as valproic acid, carbamazepine, salicylate, topiramate, or cytotoxic agents . Additionally, renal tubular acidosis, urinary tract dilatation or urinary tract infection, pregnancy, and hypoglycin may contribute to nonhepatic hyperammonemia.…”