Sudden valproate-induced hyperammonemia managed with L-carnitine in a medically healthy bipolar patient

Abstract

Rationale:Valproic Acid is a commonly used psychiatric drug primarily used as a mood stabilizer. Mild hyperammonemia is a Valproic Acid common adverse effect. This report presents an example of treated hyperammonemia on Valproic acid therapy managed with L-carnitine administration in BD patients characterized by sudden vulnerability.Patient concerns:We report the case of a 29-year-old man suffering from bipolar disorder (BD) and substance use disorder who exhibited sudden altered mental status upon admittance to the inpatient unit. The patient was started on Valproic acid with no improvement.Diagnoses:The patient had remarkably high ammonia levels (594 μg/dL) without hepatic insufficiency, likely due to his valproate treatment.Interventions:The patient was administered lactulose, intravenous hydration, and i.v. levocarnitine supplementation 4.5 g/day.Outcomes:The administration leads to reduction of ammonia levels to 99 μg/dL within 12 hours upon initiation of carnitine therapy and progressive restore of his mental status within 24 hours.Lessons:Resolution of hyperammonemia caused by Valproic acid therapy may be enhanced with the administration of L-carnitine. An interesting aspect of this case was how rapidly the patient responded to the carnitine therapy.

The Effect of Sodium Valproate on Urinary Frequency and Enuresis Compared to Carbamazepine in Children with Epilepsy

“…During the childhood, two of the most common medications in the treatment of epilepsy are sodium valproate and carbamazepine (7)(8)(9). Therefore, the aim of the current study was to investigate the role of sodium valproate monotherapy on urinary complications especially enuresis in children with epilepsy and to compare the results with carbamazepine monotherapy as well as investigation of those factors which are related to the complications.…”

“…Sodium valproate, as a wide-spectrum treatment, is one of the most prevalent medication choices in children with epilepsy. However, like other medications, it associates with different side effects such as hepatic toxicity, pancreatitis, agranulocytosis, weight gain, hyperammonemia, tremor, and hair loss (7)(8)(9). Along with the mentioned side effects, sodium valproate consumption has been shown to result in certain urinary complications such as enuresis which occurs more frequently upon the dosage increase (10-12).…”

Hypoxic respiratory failure due to hyperammonemic encephalopathy induced by concurrent use of valproic acid and topiramate, a case report and review of the literature

“…Arginine plays a critical role in ammonia detoxification, as ammonia is detoxified via its metabolism into urea. On the one hand, it has been accepted that arginine is an activator of N-acetyl glutamate synthetase (NAGS) via agmatine; on the other hand, arginine entering the liver via the portal vein is metabolized to provide ornithine for citrulline and aspartate synthesis and for the priming of the urea cycle [ 6 , 10 ]. The clinical response of our patient was correlated with the decrease in the serum ammonia level but literature has shown that serum levels of ammonium do not correlate with the severity of valproate-induced encephalopathy and there is no conclusive evidence of a major causative role of hyperammonemia on encephalopathy in human clinical studies [ [1] , [2] , [3] ].…”

“…The development of hyperammonemia, the consequences of which are difficult to differentiate from the pathology itself and that can be misdiagnosed as therapeutic failure instead of an adverse drug reaction related to the use of VPA [ 10 ].…”

Nephroprotective Role of Zinc Against the Ammonium Sulfate Toxicity in Male Albino Rats

“…Utilization in excess of nitrogenous pollutants actually enters the aquatic ecosystem and runoff from land and industrial sewage, results in toxic effect on living forms as well as terrestrial forms through the food chain, and accumulated in their body [1]. The excessive production of ammonium levels in the body is associated with the using of antiepileptic and chemotherapeutic drugs such as valproic acid, salicylate, L-asparaginase, infections, and structural defects [2,3]. Ammonium absorbed by the digestive gut is metabolized to urea in the liver and eliminated through renal organ [4].…”