Valproic acid-induced hyperammonemic encephalopathy (VIHE) in a patient with Bipolar disorder: A case report and literature review

INTRODUCTION: Valproic acid (VPA) is a valuable treatment for bipolar disorder, schizoaffective disorder, and agitation(1). However, potential side-effects include sedation, headaches, tremors, ataxia, gastrointestinal issues, neural tube defect, (3) and mild hyperammonemia even in normal liver function test (1) and VPA level. OBJECTIVES: To illustrate clinical presentation of VIHE and provide literature review on post-VIHE treatment options. METHODS: A 59-year-old male with PMH of Diabetes Mellitus, Hypertension, Hyperlipidemia, LVH, COPD, s/p CVA, and PPH of schizoaffective disorder, bipolar type. Patient stable on VPA 1250mg daily and Olanzapine 5mg daily for >2years until recent manic decompensation resulting to up-titration of VPA to 1500mg H.S. Thereafter, he presented with altered mental status, with VPA level (111.4 ug/ml), hyponatremia (119 mmol/L) and hyperammonemia (84 umol/L). Subsequently, admitted as a case of VIHE and hyponatremia. RESULTS: VPA has shown to cause hyperammonemia alone or when combined with antipsychotics(6). VIHE reported in up to 47.7% of patients on VPA(1), but symptomatic in approximately 10% of patients on VPA with blood ammonia level about 2-fold the normal range(8). VIHE presents with confusion, ataxia, blurred vision, delirium, and seizures(3). Treatment options include VPA discontinuation, switch to other mood stabilizers (lithium carbonate, lamotrigine), utilization of medications to lower blood ammonia levels (Lactulose, Rifaximin/Neomycin) ,(3) antipsychotic monotherapy, and supplements (Levocarnitine or Carglumic acid) in the prevention, maintenance, and treatment of VIHE. These supplements can be added to VPA if the benefits of re-initiating or continuing VPA outweighs the risk(3). CONCLUSIONS: Further research is needed. DISCLOSURE: No significant relationships.