(091) Neuropsychiatric Sequelae of Hyperammonemia: Clinical Pearls for the CL Psychiatrist

Abstract: Background/Significance:

Hyperammonemia is known to cause acute and chronic neurotoxicity, and one of the most well-known clinical sequelae of hyperammonemia is encephalopathy (Ali, 2022). Valproic acid (VPA) has often been associated with inducing hyperammonemia (Baddour, 2018). Discussant will review a case of a patient with altered metal status and elevated ammonia level. Literature review will cover current literature on non-hepatic hyperammonemia, clinical grading of hepatic encephalopathy, and treatment options.

Case:

A 74-year-old male with schizoaffective disorder, bipolar type, and past medical history of CKD stage III and COVID-19 associated cognitive sequelae was being evaluated for behavioral dysregulation and psychosis attributed to acute psychiatric decompensation. Home medications included benztropine, aripiprazole tabs with aripiprazole long-acting injectable as well as VPA. After confirming medication adherence and obtaining a sub-therapeutic VPA level of 44 mcg/mL on admission, the VPA dose was increased from 1500mg qhs to 1750 mg qhs to manage agitation. After initial improvement, the patient developed lethargy with altered sensorium and inattention. Work-up revealed a VPA level of 106 mcg/mL, prompting discontinuation of VPA. Additionally, labs showed an ammonia level of 38 µmol/L, which increased to 51µmol/L a few days later.

Discussion:

While encephalopathy resulting from hepatic failure is well studied, there are fewer studies on the approach to and neuropsychiatric sequelae of non-hepatic hyperammonemia, often with varied reference values. The differential diagnosis for non-hepatic causes of hyperammonemia is broad, most notable for VPA, as well as carbamazepine and inborn errors of metabolism (Kalra, 2020). Additionally, there have been case reports on the interaction between VPA and other antipsychotics such as risperidone, which may be associated with an increased risk of hyperammonemia (Davoudi-Monfared, 2019). However, guidance is limited on evaluating asymptomatic versus symptomatic hyperammonemia. Treatment options include addressing underlying etiology as well as management of active symptoms.

Conclusion/Implications:

Given the neurotoxic effects of ammonia, it is important for the Consultation-Liaison Psychiatrist to consider non-hepatic hyperammonemia as an etiology of altered mental status, especially considering the effects of medications such as VPA. Further research on the clinical presentation of non-hepatic hyperammonemia and the longitudinal effects of hyperammonemia is necessary to determine the role of trending elevated values.



References:

Davoudi-Monfared, E., Radmehr, M., Ghaeli, P., & Mousavi, M. (2019). A Case Series of Severe Hyperammonemia Encephalopathy Related to Valproate: Can Antipsychotics Increase the Risk?. Iranian journal of psychiatry, 14(3), 248–252.

Kalra A, Norvell JP: Cause for confusion: noncirrhotic hyperammonemic encephalopathy. Clin Liver Dis (Hoboken). 2020, 15:223-7.

Ali R, Nagalli S. Hyperammonemia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557504/

Baddour, E., Tewksbury, A., & Stauner, N. (2018). Valproic acid-induced hyperammonemia: Incidence, clinical significance, and treatment management. The mental health clinician, 8(2), 73–77.