A 36-year-old woman was admitted to the hospital for a second manic episode. She was first treated with diazepam, 30 mg/day, to manage agitation, and divalproex sodium, 1,000 mg/day, was added as an antimanic medication. As her clinical state worsened over the next 3 days, divalproex sodium was increased to 1,500 mg/day and olanzapine, 10 mg/day, was added. Adding an antipsychotic while gradually increasing the dose of valproate acid is recommended in the absence of signs of improvement.2 When this latest combination was started on day 4, the patient became drowsy, and therefore diazepam was stopped. However, her clinical state continued to worsen. The next morning, she gradually became comatose. All treatment was stopped, and a physical exam was performed. Electrolytes as well as liver and renal function tests were normal. Her serum valproate acid level remained in the therapeutic range according to clinical indications, at 120 mg/liter (plasma concentration for clinical response: 45–125 mg/liter).3,4 The ammonia level was 26 μmol/L [laboratory range: 11–48 μmol/liter]. Previous findings included normal brain computed tomography. Her serum valproate acid dropped to 77 mg/L, and she was deeply comatose and in a nonreactive state some hours later. An EEG was performed and showed severe encephalopathy (Figure 1; panel A). She was transferred to the medical intensive care unit where she was intubated. Twenty-four hours later, after all the treatments had been discontinued, she completely recovered. Olanzapine alone was reintroduced within 48 hours and no side effects occurred. The EEG performed 12 days after the encephalopathy was normal (Figure 1; panel B). The patient was discharged taking 20 mg/day olanzapine alone.