---
title: "Psych News Alert: Low-Dose, Off-Label Exposure to Some Antipsychotics May Increase Risk of Cardiometabolic Death"
description: People taking off-label, low doses of the antipsychotics olanzapine or quetiapine for more than six months may be at higher risk of death d...
image: https://alert.psychnews.org/hubfs/Imported_Blog_Media/doctor_patient_pills_iStock-1041147612-Jun-24-2025-07-37-45-5626-PM.jpg
---

 11/17/21 12:00 AM

# Low-Dose, Off-Label Exposure to Some Antipsychotics May Increase Risk of Cardiometabolic Death

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People taking off-label, low doses of the antipsychotics olanzapine or quetiapine for more than six months may be at higher risk of death due to cardiometabolic complications than people not taking these medications, according to a [report](https://www.sciencedirect.com/science/article/pii/S0022395621006725) in the *Journal of Psychiatric Research*.

“Off-label” use of antipsychotics (meaning prescribing an FDA-approved drug for an unapproved use) has become extremely common, despite limited evidence of effectiveness, wrote Jonas Berge, M.D., of Lund University in Sweden and colleagues. Additionally, studies have shown that olanzapine and quetiapine are associated with cardiometabolic complications—obesity, dyslipidemia, hyperglycemia, hypertension—that can lead to death.

Using Swedish national registries, the researchers identified adults 18 years and older who had at least one psychiatric visit (inpatient or outpatient) between July 2006 and December 2016. People who had previous diagnoses of bipolar, psychotic, or cardiometabolic disorders and/or who were prescribed antipsychotics or drugs indicated for cardiometabolic-related reasons prior to the study period were excluded from the analysis. A total of 428,525 individuals (average age: 37 years) were followed for 10.5 years; of these, 18,317 were treated with low-dose olanzapine or quetiapine, defined as 5 mg/day or less. By the end of the study, 13,358 of the cohort died during the observation time.

Berge and colleagues compared cardiometabolic death outcomes in those taking low-dose olanzapine or quetiapine for six months or less, six to 12 months, and more than 12 months.

In total, 2,606 cardiometabolic-related deaths occurred. Compared with no treatment, treatment for less than six months was associated with a significantly lower risk of cardiometabolic death. However, people treated for six to 12 months had a 1.89 times higher risk of cardiometabolic death than those not treated. (There was a slightly higher risk of death for those treated more than 12 months, but it was not statistically significant.)

Among those treated, each year of exposure to an average dosage of 5 mg/day was associated with a 1.45 times higher risk of death, according to the report.

“Clinicians ought to be aware of potential cardiometabolic consequences [of off-label exposure to low-dose olanzapine or quetiapine],” the researchers wrote. “Before prescribing, a thorough risk-benefit analysis should be performed, with screening and follow-up being well employed regardless of prescribed dose or length of treatment.”

For related information, see the *Psychiatric News* article “[Special Report: Guidance on Managing Side-Effects of Psychotropics](https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2021.8.30).”

(Image: iStock/SDI Productions)

---

### REIMAGINE: A Week of Action to Reimagine National Response to People in Crisis

APA is pleased to be a partner in [REIMAGINE: A Week of Action to Reimagine Our National Response to People in Crisis](https://reimaginecrisis.org/), which kicked off Monday and continues through Friday, November 19. Each day features different speakers and topics, with the goal of exploring the impact of our current inadequate response to people in crisis and how to advocate to change things for the better. Please participate and invite others in your district branch to participate as well.

[LEARN MORE](https://reimaginecrisis.org/)

[obesity](https://alert.psychnews.org/tag/obesity), [olanzapine](https://alert.psychnews.org/tag/olanzapine), [Journal of Psychiatric Research](https://alert.psychnews.org/tag/journal-of-psychiatric-research), [quetiapine](https://alert.psychnews.org/tag/quetiapine), [dyslipidemia](https://alert.psychnews.org/tag/dyslipidemia), [antipsychotics](https://alert.psychnews.org/tag/antipsychotics), [off-label use](https://alert.psychnews.org/tag/off-label-use), [hypertension](https://alert.psychnews.org/tag/hypertension), [hyperglycemia](https://alert.psychnews.org/tag/hyperglycemia)

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