Fatality from Olanzapine Induced Hyperglycemia

Abstract

A case history of a 31-year-old male schizophrenic patient is presented. The man was treated with olanzapine for three weeks be-fore he died. After one week on a 10 mg daily dose of olanzapine, his fasting blood glucose was elevated to 11.3 mmol/L (203 mg/dL). In order to treat more aggressively his psychosis, the olanzapine dose was raised to 20 mg daily resulting in his fasting blood glucose climbing to 15.8 mmol/L (284 mg/dL). On the days preceding his death, he became progressively weaker, and developed polydipsia with polyuria. He had no personal or family history of diabetes mellitus and he was on no other medication at the time of his death. Postmortem blood, vitreous humor, and urine glucose concentrations were 53 mmol/L (954 mg/dL), 49 mmol/L (882 mg/dL), and 329 mmol/L (5922 mg/dL), respectively. Drug screen on urine and blood indicated only a small amount or olanzapine and no alcohols. Peripheral blood olanza-pine concentration was within therapeutic limits, 45 ng/mL. Analysis of vitreous humor and urine revealed severe dehydration with small amounts of ketones. Death was attributed to hyperosmolar nonke-totic diabetic coma, and olanzapine was felt most likely to be the cause. Another atypical neuroleptic, clozapine, has also been associated with the development and exacerbation of diabetes mellitus or diabetic ke-toacidosis. We recommend including vitreous glucose and -hydroxybutyrate analysis as part of postmortem toxicology work up when the drug screen reveals the presence of either olanzapine or clozapine.

A severe case of olanzapine overdose with analytical data

“…Although our patient had no history of previous diabetes mellitus, the blood glucose concentration reached 350 mg/dL at eight hours after being found. High blood glucose levels were reported at both toxic and therapeutic doses of olanzapine, associated with hyperosmolar nonketotic diabetic coma or with ketoacidosis, even resulting in death (17)(18)(19). Other features in our patient included respiratory depression with aspiration pneumonia secondary to altered mental status, which required a protected airway and intubation, also described by others (9,20).…”

An update of safety of clinically used atypical antipsychotics

“…haloperidol), cases of NMS have been also described with each atypical AP [80,107]. It has been reported following the use of risperidone [170], olanzapine [124], iloperidone [108], clozapine [80], asenapine [171] and aripiprazole [172]. Clozapine-related seizures are dosedependent, particularly higher at >600 mg/day [72][73].…”

“…Regular physical activity, smoking cessation and nutrition management could be helpful. A potential LT AEs may be represented by hyperglycemia which in some cases may be associated with ketoacidosis/hyperosmolar coma or death [124].…”

Do Certain Atypical Antipsychotics Increase the Risk of Diabetes? A Critical Review of 17 Pharmacoepidemiologic Studies

“…However, some atypical antipsychotics have been linked to potentially serious metabolic adverse effects, including weight gain, type 2 diabetes mellitus, hyperglycemia, and diabetic ketoacidosis (4)(5)(6)(7)(8)(9). Most case reports of diabetes and diabetic ketoacidosis involve clozapine and olanzapine (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), whereas a smaller number involve risperidone and quetiapine (17,(30)(31)(32)(33)(34)(35). To date, no reports have involved ziprasidone or aripiprazole, but patient exposure to these drugs is limited (36).…”