The cardiometabolic risks add up
STUDY: Radha Krishnan RP et al, Psychiatry Research 2026
STUDY TYPE: Systematic review
FUNDING: Australian National Health and Medical Research Council
Background
Researcher have warned about off-label antipsychotics for decades, but the rates continue to grow. Quetiapine for insomnia, olanzapine for anxiety, risperidone for irritability. This study looks at the risks with the lower doses typically used outside of psychosis.
The Study
- Systematic review of 13 observational studies, all lasting at least a year (average three).
- Adults and the elderly with non-psychotic disorders, including major depression, intellectual disability, autism spectrum disorder, dementia, and Tourette’s syndrome.
Results
Adults on antipsychotics showed higher rates of weight gain (29–78%), high blood sugar (5–23%), and dyslipidemia (16–48%) compared to untreated patients. Metabolic problems were worse for second- than first-generation antipsychotics.
In terms of heart disease, a Swedish registry study of 428,525 patients found a weak link between low-dose olanzapine or quetiapine and death from cardiometabolic causes, with hazard rising about 45% for each additional year of exposure at 5 mg/day.
In elderly patients with dementia, twice as many had metabolic syndrome on antipsychotics vs off (27% vs 14%).
Children
Children are more prone to metabolic risks on antipsychotics, so the authors analyzed them in a separate paper. Among 15 observational trials, long-term antipsychotics in non-psychotic disorders caused weight gain (91.6% studies, n = 12), hyperglycaemia (100%, n = 6), dyslipidemia (66.6%, n = 6), metabolic syndrome (100%, n = 2), and possibly hypertension (25%, n = 4). No studies looked at heart disease.
Limitations
All observational studies, as no randomized controlled trials lasted long enough.
Practice Implications
- Antipsychotics are risky meds, deserving serious consideration of whether they work, and whether those benefits are short vs long-term.
- Although these risks are significant with low doses, they are worse in the higher range.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
