Polypharmacy: a risk factor to consider in valproate‐induced hyperammonaemic encephalopathy

Background Valproate is commonly prescribed as part of combination therapy in antiepileptic or mood stabilising regimens. Although generally well tolerated, valproate has potential to cause serious adverse effects, one of which is valproate‐induced hyperammonaemic encephalopathy (VHE). The risk of developing VHE is rare; however, this can increase when valproate is used in conjunction with other medications. Aim This report aims to highlight the importance of early diagnosis of VHE and emphasise the potential deleterious effects of polypharmacy and certain hazardous drug combinations. Clinical details A 58‐year‐old woman with a 1‐week history of increasing lethargy, confusion and drowsiness presented to the emergency department. Blood tests showed a raised ammonia level and liver function test (LFT) derangement. She had been on a long‐term antiepileptic regimen which included sodium valproate. The only recent change to her medications was the introduction of atorvastatin. A diagnosis of VHE was made and valproate was discontinued. Atorvastatin was also stopped on account of its likely role in LFT derangement. Outcomes After discontinuation of both agents attributed to her presentation, serum ammonia and LFTs returned to within normal range. The patient also gradually resumed her usual level of alertness and functional state. Conclusion This report describes a case of VHE and emphasises the detrimental role of polypharmacy associated with this presentation. This illustrates the potentially complex pharmacy issues that must be considered in the management of a patient on chronic valproate therapy.