The Physical Toll of Antipsychotics

Patients with severe mental illnesses, such as schizophrenia and bipolar disorder, rely on long-term use of antipsychotic medications to control their condition. But concerns are growing that those same medications put patients at higher risk of other diseases. Confirmation has come from Professor Francisco Lai Tsz-tsun of HKUMed’s Department of Pharmacology and Pharmacy, and the Department of Family Medicine and Primary Care, School of Clinical Medicine, who has led some of the largest investigations to date on the problem, involving data from tens of thousands of patients.

Over the past 18 months, Professor Lai and his colleagues have shown that long-term use of the drug clozapine, effective for treatment-resistant schizophrenia, carries a 25 per cent higher risk of developing respiratory, gastrointestinal and other infections, and a slightly higher risk of developing blood cancers. Prolactin-raising drugs, meanwhile, double the risk of developing gynaecological cancers, although that risk is still rare.

Previously, Professor Lai demonstrated in his PhD and postdoctoral work that women using antipsychotics had about a 32 per cent higher risk of ischemic heart disease compared with those who do not use the drugs.

“Our goal is to interpret both relative and absolute risks in the clinical context and to provide actionable recommendations for monitoring and prevention, so patients can benefit from these effective medications while keeping potential risks within acceptable limits,” he said.

“I’m also motivated by the overarching idea that a significant proportion of physical illnesses are preceded by mental illnesses. So if we have good interventions or early detections of mental health issues, we can address a lot of physical health problems.”

Weakened immunity

Each of the recent studies uses large datasets to get a comprehensive picture. The side effects of clozapine are of particular interest because it is the only drug approved by the US Food and Drug Administration for treatment-resistant schizophrenia. Professor Lai and his team looked at data from more than 10,000 patients with schizophrenia in Hong Kong for two studies of the drug.

The first, published in late 2024, showed a slightly elevated risk for blood cancers such as leukaemia and lymphoma. It prompted the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee to require pharmaceutical companies to submit additional safety data and update their product information in Europe.

The results inspired the second study, published in September 2025 in The Lancet Psychiatry, where the team considered if the haematologic abnormalities they had seen in the blood cancer study – reduction in white blood cells – would weaken the immune system. This was confirmed, indicating that patients taking the drug had a higher infection risk. The risk was greatest among patients aged 55 or above.

“Since clozapine may be the only option for patients, it would be unrealistic if we recommended against using it. But it might be appropriate to monitor a wider range of risks for this group. For instance, doctors could encourage vaccinations, try to detect symptoms earlier and encourage better infection prevention,” he said.

Holistic view needed

The study on prolactin-raising drugs, commonly used as antipsychotics, was also published in September 2025 in World Psychiatry. Using a dataset of more than 80,000 women in Hong Kong who were new users of antipsychotic medications, the team found prolactin-raising drugs nearly doubled the risk of gynaecological cancers to about one in 2,300.

“It is still a pretty rare chance of having this cancer, and prolactin-increasing drugs are actually being phased out. But women with a family history or other risk factors should make informed decisions with their doctor about monitoring and follow-up,” he said.

Overall, both studies point to the need for doctors to consider their patients’ health after psychotic symptoms are under control, through monitoring and early detection, so nothing more serious happens to them.

Professor Lai is now starting to replicate these studies in other populations, for instance, with insurance claims data from a private Japanese firm and other data from the UK. Hong Kong has been a strong starting point, though, because the data is highly reliable due to consistent standards and practices in the Hospital Authority and its dominant role in healthcare here.

He also has funding to investigate drug interactions with Chinese medicine, in particular chai hu (bupleurum root), which is used in formulas for common illnesses such as cold and fever, as well as psychiatric symptoms.

This is all unusual territory for the former economics student, who switched to public health in his postgraduate studies. “I think my non-clinical background gives me an advantage because I focus on things that a layman or patient might be concerned about,” he said.