Fatal Olanzapine-Induced Ketoacidosis

Mr. A, a 45-year-old man with a 29-year history of bipolar disorder with psychotic features, polysubstance abuse, and no history of diabetes, died in December 2001. The cause of death was ascertained to be diabetic ketoacidosis; the postmortem vitreous glucose level was 743 mg/dl, and the blood was positive for acetone (concentration, 0.03%). Mr. A was 72 inches tall and weighed 214 lb. He was of mixed race, part African American. Treatment with olanzapine, 30 mg/day, had been restarted 1 month before Mr. A’s death. He had been treated with it on two previous occasions for less than 2 weeks; each time, treatment ended because of noncompliance. At the time olanzapine treatment was restarted, routine testing showed his blood sugar level to be normal. At the time of death he had also received prescriptions for risperidone (6 mg/day), lithium (1800 mg/day), fluoxetine (20 mg/day), and bupropion (400 mg/day). He was living with family members who insisted that he take his medication, and he had not been seen psychiatrically since restarting olanzapine treatment. The family did not observe warning signs of ketoacidosis. He had a history of alcohol, crystal methamphetamine, and occasional cocaine abuse, but postmortem toxicology studies were negative for all three substances.