Olanzapine-Induced Ketoacidosis With Diabetes Mellitus

Mr. A was a 50-year-old, single, African American man with a 30-year psychiatric history with multiple psychiatric hospitalizations. He had been admitted to Manhattan Psychiatric Center 20 years earlier and had been hospitalized continuously since then. His diagnoses included schizophrenia (paranoid type), substance dependence, and antisocial personality disorder. He had a significant history of criminal and deviant sexual behavior. His medical history included hypertension, mild obesity (227 lb), and myocardial infarction but not diabetes. He had been on a regimen of extended-release nifedipine, 30 mg/day, to control his hypertension. He did not have a significant family history of diabetes.

During Mr. A’s hospitalization, a variety of anti­psychotic medications were used, including fluphenazine decanoate, 25 to 75 mg i.m. every 2 weeks, chlorpromazine, 1800 mg/day, and haloperidol, 40 mg/day. He had no major side effects from these drugs. Mr. A had also received divalproex sodium, 750 mg twice a day, for 2 years. His psychiatric disorder had remained resistant to conventional antipsychotic medications. He refused to take clozapine because of the blood testing that was required. The results of his annual laboratory tests in 1997, including his blood sugar level, were normal.

Mr. A started olanzapine treatment, 5 mg/day. He continued to receive fluphenazine decanoate, 75 mg i.m. every 2 weeks, and divalproex sodium, 750 mg twice a day. His olanzapine dose was then gradually titrated to 30 mg/day over 6 months with the intent of gradually tapering his dose of fluphenazine decanoate once he was stable. His delusions and paranoid symptoms improved with this therapy. His weight was 227 lb at the start of olanzapine treatment, it increased to 248 lb after 5 months, and then it went down to 205 lb at the end of treatment. That same month, Mr. A was found drowsy, lethargic, and unresponsive to verbal commands. His blood pressure was 98/68 mm Hg, and he had orthostatic hypotension. Mr. A was then transferred to a hospital emergency room and later admitted to the intensive care unit for diabetic ketoacidosis; he had a blood sugar level of 1200 mg/dl. He was given intravenous insulin and 5% dextrose fluid.

Mr. A’s olanzapine regimen was discontinued, and his diabetic ketoacidosis disappeared. He received human insulin (NPH), 40 to 70 units for 15 days. His insulin treatment was then discontinued, with subsequent normalization of his blood sugar level. His levels of blood sugar, urine sugar, and acetone remained normal. He remained on a regimen of fluphenazine decanoate, 75 mg i.m. every 2 weeks, benztropine mesylate, 2 mg twice a day, and divalproex sodium, 750 mg twice a day. Both the manufacturer of olanzapine and the Food and Drug Administration’s MedWatch were notified of his drug reaction.