Understanding heart damage from schizophrenia medication could save lives

Published: 1 July 2024

A young researcher is investigating why a highly effective medication for treatment-resistant schizophrenia may cause damage to the heart or premature death.

Clozapine is a medication for treating schizophrenia that’s used as a last line of resort when other medications haven’t been effective. This highly effective schizophrenia medication can significantly improve people’s quality of life and reduce the risk of suicidality. Unfortunately, it can also damage the heart.

Amanda Groenewald will be researching this in her Doctor of Philosophy (PhD) at the University of Auckland, thanks to the A. H. Couch Trust Heart Foundation Scholarship. The Heart Foundation and the A. H. Couch Trust are working in partnership to support promising cardiology trainees and researchers who are carrying out heart research in Aotearoa New Zealand.

Amanda’s research aims to investigate the cellular mechanisms which may result in heart damage. New knowledge from this study could help develop better diagnostic tests for at-risk patients and early detection of heart damage, as well as more effective targeted treatments.

“I’m passionate about the potential of this research to benefit people with schizophrenia and help reduce the side effects on the heart of this valuable medication,” explains Amanda.

Adverse effects on the heart from clozapine are serious and often life-threatening, including myocarditis and cardiomyopathy, as well as arrhythmias and sudden cardiac death. The reasons it damages the heart are unknown, although there is an increased risk for people who are also on sodium valproate, an anticonvulsant and mood stabiliser medication.

“The relationship between heart damage and clozapine, particularly in combination with sodium valproate, isn’t well understood and more insight into how it occurs is an important first step in changing that,” says Dr Gerry Devlin, Heart Foundation Medical Director.

Amanda will test these medications in isolated human heart tissue obtained from consenting patients undergoing routine surgery. Her research will utilise exciting new technology – the MyoDish tissue culture system – that enables her to study the schizophrenia medication effects on heart tissue over days to weeks. The system is the first of its kind in New Zealand and was funded by a Heart Foundation grant in 2023.

Findings from her research have the potential to inform future clinical decisions, such as guidelines on detection and treatment of clozapine toxicity in the heart. Understanding the mechanisms behind the effect of clozapine on the heart may also apply to other drugs.

The A.H. Couch Trust is excited to support talented young researchers like Amanda. “We have every confidence in her ability to become an outstanding researcher, scientist and role model,” say the trustees.

The A. H. Couch Trust was established in 1972 through the generosity of the late Arthur Herbert Couch after he survived a serious heart attack.