OBJECTIVES:To review signs and symptoms of valproate-induced hyperammonaemic encephalopathy without hepatotoxicity in the psychiatric setting, explore its mechanisms, and give recommendations for prevention and treatment. METHODS:Medline search with keywords valproate, ammonia, hyperammonaemia, encephalopathy, and then cross-references to articles obtained through this search. Only cases with indication of valproate for psychiatric condition were included. RESULTS:Fourteen cases published in the psychiatric setting are reviewed. Valproate-induced hyperammonaemic encephalopathy is a rare adverse event, occurring almost equally in men and women, with a large age range, and reported in two patients with mental retardation. Symptoms appeared either a few days after initiation of valproate therapy, or after several months or years. The main symptoms were fluctuations in consciousness and disorientation. Clinical severity was not related to blood ammonia levels. All patients recovered after valproate-induced hyperammonaemic encephalopathy diagnosis and treatment, usually involving discontinuation of valproate. CONCLUSIONS:Valproate-induced hyperammonaemic encephalopathy is rare and usually reversible in patients without urea cycle disorders when valproate is discontinued. Therapy with carnitine is recommended. Special caution should be used in patients with mental retardation. Psychiatrists should suspect valproate-induced hyperammonaemic encephalopathy when consciousness deteriorates.