Surreal illustration of air escaping from a pill bottle, representing medical complications.

Deadly Mix: When Olanzapine Turns Fatal – Understanding the Risks

Theo Raines in Health & Wellness December 2025 • 4 min read.

"A rare case highlights the dangers of olanzapine-induced ketoacidosis and the importance of comprehensive postmortem investigations."

Olanzapine is a widely prescribed atypical antipsychotic medication used in the treatment of schizophrenia and bipolar disorder. While effective, it carries potential risks, including metabolic disturbances such as insulin resistance, hyperglycemia, and, in rare cases, life-threatening diabetic ketoacidosis (DKA).

DKA is a severe complication where the body produces excess blood acids (ketones). While pneumomediastinum (PM) and subcutaneous emphysema (SE) are recognized complications of DKA, a recent case reveals a particularly dangerous scenario involving olanzapine. PM and SE occur when air leaks into the mediastinum and tissues under the skin, respectively, often due to increased pressure from vomiting or Kussmaul breathing associated with severe DKA.

This article delves into a recent fatality where olanzapine-induced ketoacidosis led to the discovery of PM and SE during a postmortem computed tomographic (CT) scan, highlighting the critical need for enhanced awareness and comprehensive investigation in similar cases.

The Case Unveiled: Olanzapine-Induced Ketoacidosis

Surreal illustration of air escaping from a pill bottle, representing medical complications.

A man in his forties, with a history of depression and substance use disorder, was found deceased. The scene indicated a possible overdose, with empty capsules of olanzapine and flunitrazepam discovered nearby. The postmortem CT scan revealed PM and SE extending from the lower face to the first rib.

The autopsy confirmed congested internal organs, and notably, the CT scans ruled out other causes such as trauma or disease. Toxicological analysis pointed towards a high concentration of olanzapine in the femoral blood, far exceeding therapeutic levels.

Blood tests revealed elevated levels of 3-hydroxybutyric acid (3328 µmol/L) and acetone (0.57 mg/dL), indicative of severe ketoacidosis.
Urine samples showed extremely high concentrations of 3-hydroxybutyric acid (29,873 µmol/L) and acetone (8.7 mg/dL), reinforcing the diagnosis.
Drug screening identified olanzapine, flunitrazepam, amphetamine, and methamphetamine, with olanzapine at a potentially fatal concentration of 0.89 µg/mL.

The ultimate cause of death was attributed to ketoacidosis, most likely induced by olanzapine intoxication. This case underscores the potential for olanzapine to trigger severe metabolic imbalances, even in individuals without a prior history of diabetes.

Key Takeaways: Vigilance and Comprehensive Analysis

This case highlights the critical importance of considering olanzapine-induced ketoacidosis in sudden and unexplained deaths, especially in patients undergoing treatment with this medication. The presence of pneumomediastinum and subcutaneous emphysema on postmortem CT scans should prompt thorough toxicological investigations.

Early detection and intervention are crucial in managing olanzapine-related complications. Clinicians should be vigilant about monitoring patients for signs of metabolic disturbances and ketoacidosis, particularly when initiating or adjusting olanzapine dosages.

Comprehensive postmortem investigations, including CT scans and toxicological analyses, are essential in accurately determining the cause of death and identifying potential drug-related fatalities. This approach not only aids in individual cases but also contributes to a better understanding of drug safety and informs clinical practice.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/1556-4029.13942, Alternate LINK

Title: Olanzapine‐Induced Fatal Ketoacidosis With Pneumomediastinum And Subcutaneous Emphysema

Subject: Genetics

Journal: Journal of Forensic Sciences

Publisher: Wiley

Authors: Suguru Torimitsu, Yohsuke Makino, Kanju Saka, Yusuke Fujii, Hiroko Abe, Fumiko Chiba, Rutsuko Yamaguchi, Hirotaro Iwase

Published: 2018-10-29

Everything You Need To Know

What is Olanzapine, and what is its purpose?

Olanzapine is an atypical antipsychotic medication primarily used to treat schizophrenia and bipolar disorder. It works by affecting the levels of certain chemicals in the brain, helping to stabilize mood and reduce psychotic symptoms. However, olanzapine has potential side effects, including metabolic disturbances that can lead to severe health complications such as diabetic ketoacidosis.

What is diabetic ketoacidosis, and why is it important in the context of olanzapine?

Diabetic ketoacidosis (DKA) is a severe and potentially life-threatening complication of diabetes where the body produces excessive ketones, leading to a dangerous increase in blood acidity. In the context of olanzapine, it is a significant risk because olanzapine can disrupt the body's metabolism, potentially leading to insulin resistance and the development of DKA, even in individuals without a prior history of diabetes. This is significant because DKA can rapidly lead to severe health complications, including organ damage, and can be fatal if left untreated.

What are pneumomediastinum and subcutaneous emphysema, and what is their significance?

Pneumomediastinum (PM) is a condition where air leaks into the mediastinum, the space in the chest between the lungs, while subcutaneous emphysema (SE) occurs when air gets trapped under the skin. In the presented context, PM and SE were observed in a case of olanzapine-induced ketoacidosis. The increased pressure from vomiting or Kussmaul breathing associated with severe DKA can cause these conditions. Recognizing these conditions on postmortem CT scans is critical because it can indicate severe metabolic disturbance and prompt the need for thorough toxicological analysis to determine the underlying cause of death.

Why is the detection of high concentrations of olanzapine significant in a postmortem investigation?

The discovery of high concentrations of olanzapine in a postmortem investigation is crucial. This is because olanzapine can induce diabetic ketoacidosis, a life-threatening metabolic imbalance. If a person is found deceased with unexplained symptoms and olanzapine is detected, it raises strong suspicion of olanzapine-induced ketoacidosis. Comprehensive postmortem investigations, including toxicological analysis, are necessary to determine the role of olanzapine in the death. This is particularly important in cases of sudden and unexplained deaths.

What are the key takeaways from this information?

The key takeaways are the importance of vigilance and comprehensive analysis when investigating sudden and unexplained deaths. It highlights that olanzapine-induced ketoacidosis should be considered in individuals taking the medication. The presence of pneumomediastinum and subcutaneous emphysema on postmortem CT scans necessitates thorough toxicological investigations. This reinforces the critical need for forensic pathologists to conduct thorough investigations, including detailed examinations and toxicological analyses to determine the cause of death accurately, especially in cases where olanzapine use is suspected.