Japan Study: Common Antipsychotics May Raise Pancreatitis Risk

Japanese Research Flags Pancreatitis Risk From Common Antipsychotic Medications

A study from Japan published in the Journal of Affective Disorders raises an important warning for people living with diabetes who are also prescribed certain psychiatric medications. Researchers at Gifu Pharmaceutical University analyzed nearly a decade of Japanese insurance claims data to examine whether a class of antipsychotic drugs — called multi-acting receptor-targeted antipsychotics, or MARTAs — increases the risk of acute pancreatitis.

What Are MARTAs?

MARTAs are a group of second-generation (atypical) antipsychotic medications commonly prescribed for schizophrenia, bipolar disorder, and other psychiatric conditions. The drugs studied include:

• Asenapine (brand name: Saphris)
• Olanzapine (brand name: Zyprexa)
• Quetiapine (brand name: Seroquel)
• Clozapine (brand name: Clozaril)

These medications are already known to cause metabolic side effects — including weight gain and elevated blood sugar — which are particularly concerning for patients with or at risk for type 2 diabetes.

What the Study Found

Using a method called sequence symmetry analysis on data from 2014 to 2023, researchers compared when patients started their antipsychotic medication versus when they were diagnosed with pancreatitis. The findings were striking:

• Clozapine showed the highest risk — patients were about 6 times more likely to develop pancreatitis after starting the drug
• Olanzapine was associated with roughly 3 times the risk
• Quetiapine was linked to about 2.3 times the risk
• Asenapine carried approximately 1.8 times the risk

All four medications showed a statistically significant increase in pancreatitis risk — meaning these results are unlikely to be due to chance.

Timing Matters: Risk Builds Slowly

One of the most important findings is when pancreatitis tended to develop. It wasn't immediate — the median time from starting the medication to pancreatitis diagnosis ranged from about 20 months (612 days) for olanzapine and quetiapine up to nearly 29 months (864 days) for clozapine. This slow buildup means patients and doctors may not immediately connect the medication to the problem.

What Makes This Japanese Study Unique

Large-scale claims database studies like this are less common in the US for psychiatric medication safety monitoring. Japan's centralized healthcare data system allowed researchers to track over 9 years of real-world prescribing patterns across a broad population. While US guidelines from the American Diabetes Association (ADA) do warn that atypical antipsychotics can worsen glycemic control, specific pancreatitis risk benchmarks of this magnitude are not yet prominently featured in standard US prescribing guidance.

Why This Matters for US Patients

If you have diabetes — or are at risk for it — and you take any of these antipsychotic medications, this research suggests you and your healthcare team should be watchful for pancreatitis symptoms, which can include sudden severe abdominal pain, nausea, and vomiting. The risk appears especially elevated in people who are also obese or have high triglycerides. Because these drugs can also raise blood sugar, keeping tight track of your glucose levels is essential. Tools like continuous glucose monitors and structured diabetes management support available at mdsdiabetes.com can help you and your care team stay ahead of metabolic changes before they become serious complications.

Talk to Your Doctor If You:

• Take olanzapine, quetiapine, clozapine, or asenapine
• Have diabetes, prediabetes, obesity, or high triglycerides
• Experience unexplained abdominal pain or nausea

Never stop a psychiatric medication without consulting your prescriber — but do bring this research to your next appointment.

Citation

Noguchi, Oonishi, Masuda (2026). Analysis of acute pancreatitis caused by multi-acting receptor-targeted antipsychotics using the Japanese claims database. Journal of Affective Disorders. PMID: 41110667. DOI: 10.1016/j.jad.2025.120496. [Country of Origin: Japan] — Gifu Pharmaceutical University, Gifu, Japan.