Study aims to make schizophrenia medication safer for patients

A study funded by Health and Care Research Wales aims to make schizophrenia treatment safer by calling for the introduction of routine antibody testing for patients taking clozapine.

To mark Schizophrenia Awareness Day (25 July 2025), researchers and a participant in the SIROC study discuss how this simple, cost-effective change could transform patients’ quality of life.

Schizophrenia is a common and devastating mental illness affecting 1 in 100 of the population. Patients with treatment-resistant schizophrenia may be prescribed the anti-psychotic clozapine. However, despite being highly effective, people taking clozapine are at an increased risk of serious, recurrent chest infections. This can cause them to frequently become unwell as well as worsening their schizophrenia. 

Researchers from the Immunodeficiency Centre for Wales, based at the University Hospital of Wales in Cardiff, established a link between taking clozapine and antibody deficiency. Antibodies are a key part of the body’s immune system that help us fight off infection. The team is now calling for antibody testing as a routine part of clozapine monitoring. 

Dr Mark Ponsford, Consultant Immunologist and Principal Investigator for the SIROC study explained, 

Clozapine is the only licenced drug for treatment-resistant schizophrenia and has been for the last 30 years. We found that the rate of antibody deficiency in patients taking clozapine was approximately twice as high as expected in the general population.”

The SIROC team went on to use the SAIL Databank, also funded by Health and Care Research Wales, which holds anonymised healthcare data from patients from across Wales, to examine infection rates in adults receiving antipsychotic medications. 

Patients taking clozapine already have regular blood tests, making it relatively simple to introduce additional screening of samples to monitor antibody levels. Mark continued, “Remarkably to us, despite extensive and regular blood testing, antibody deficiency isn’t considered at present. The idea of using leftover samples was flagged to us by one of the patients themselves, which shows how vital it is to involve patients in designing the study, as they can bring so much important insight and lived experience to the design. 

We are proud to have established this link, which was first suggested in work by SIROC Chief Investigator, Professor Stephen Jolles. He recognised that a simple liver function test can help prompt recognition of immunodeficiency. This test costs as little as 17 pence. This is a simple, low-cost change which could have a significant impact on patients’ lives.

“Now that we have established this link, we would like to see it better recognised, including as a medication alert for clozapine by the Medication and Healthcare products Regulatory Agency (MHRA), which collects and monitors safety concerns related to healthcare products.”

The study team worked closely with the Immunodeficiency Centre for Wales’ patient representative group, including Group co-chair Cara Jenkins, 42, from Cardiff, who was diagnosed with a type of immunodeficiency called Common Variable Immunodeficiency (CVID) in 2011.

Cara said, “Immunodeficiency is an invisible condition, which makes it so difficult to identify. Before I was diagnosed, I was so unwell with repeated infections. It was almost constant. 

“Once I started treatment my quality of life just transformed. Thankfully my condition was caught before I developed lung damage which may immunodeficient patients develop. 

“There are so many people in Wales yet to be diagnosed with antibody deficiency, including people with schizophrenia who are taking this medication, who would benefit from life-changing antibody treatment but they just don’t know yet.” 

Cara, who also has previous experience of taking antipsychotic medication, is passionate about the importance of research in progressing treatment for immunodeficiency and mental illness. 

She continued, “It means a lot to be involved in this research, to further knowledge of a condition people may have less awareness of, and which joins up mental and physical health. Having seen the benefits of immunotherapy myself, I really believe it could transform patients’ lives in the future.”