Patients with severe mental illnesses, such as schizophrenia and bipolar disorder, often require long-term use of antipsychotic medications. Some of these drugs, however, can pose potential risks, such as elevated prolactin levels and compromised immune function. Previous studies have relied mostly on small or single-centre data, making it difficult to accurately assess the true incidence of rare adverse effects. Researchers from the LKS Faculty of Medicine at the University of Hong Kong (HKUMed), through multidisciplinary collaboration and rigorous epidemiological methods, leveraged territory-wide data from the Hospital Authority to conduct two internationally impactful studies. The findings were published in leading psychiatric journals World Psychiatry and The Lancet Psychiatry. These discoveries provide solid evidence for drug regulation and clinical practice and establish Hong Kong as a global leader in big data research on psychiatric medication safety.
The research team analysed data from over 80,000 women in Hong Kong who were new users of antipsychotic medications. They found that long-term use of prolactin-raising drugs (commonly used antipsychotics, such as risperidone and haloperidol) was associated with nearly double the risk of developing gynaecological cancers—including endometrial and ovarian cancer—compared to those taking prolactin-sparing medications. In practical terms, for every 2,300 women taking these medications long term, there may be one additional case of gynaecological cancer. Although this risk remains rare, the findings are especially relevant for women with a family history or other risk factors, helping doctors and patients make informed decisions about monitoring and follow-up.
Another study covered more than 10,000 patients with schizophrenia in Hong Kong. The results showed that those taking clozapine—a potent antipsychotic—had about a 25% higher risk of developing various infections (such as respiratory tract infections and gastroenteritis) than those taking olanzapine, another commonly used antipsychotic. In real terms, for every 100 clozapine users, there may be one to two additional cases of infection each year. This risk was particularly pronounced among patients aged 55 or above, who were much likelier to require medical attention for infections than younger patients. The study recommends that doctors prescribing clozapine strengthen infection monitoring, encourage vaccinations and promptly address infection symptoms.
These two large-scale, real-world studies provide important evidence for psychiatric medication safety. For older women or those with a family history of gynaecological cancer, doctors may consider prescribing prolactin-sparing antipsychotics or enhance monitoring and screening. For clozapine users—especially older adults—regular blood tests should be complemented by routine assessments of respiratory symptoms, vaccination against influenza and pneumococcal disease, and timely management of infections.
‘We recommend working closely with health authorities, the Hospital Authority and regulatory bodies to establish a “learning healthcare system” for medication safety. This would enable big data research to be rapidly translated into clinical guidelines and policy, improving psychiatric medication safety locally and globally,’ commented Professor Francisco Lai Tsz-tsun, Assistant Professor in the Department of Pharmacology and Pharmacy and the Department of Family Medicine and Primary Care, School of Clinical Medicine, HKUMed.
Earlier, big data research conducted by the team in Hong Kong found that clozapine may slightly increase the risk of blood cancers (such as leukaemia and lymphoma). This finding was officially cited by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (EMA PRAC) in February 2025, prompting the EMA to require pharmaceutical companies to submit additional safety data and update their product information in Europe. This international regulatory action demonstrates the real-world impact of Hong Kong's big data research on global medication safety. These two new studies continue this line of research, improving the safety profile of clozapine and other antipsychotic medications in real-world use.
‘Hong Kong's big data offers unique advantages in completeness, continuity and population coverage, making it one of the few platforms worldwide capable of accurately quantifying rare drug side effects,’ said Professor Lai. ‘Our goal is to interpret both relative and absolute risks in clinical contexts and to provide actionable recommendations for monitoring and prevention, ensuring that patients can benefit from effective medications while keeping potential risks within acceptable limits.’
The HKUMed research team, led by Professor Francisco Lai Tsz-tsun (right), uses Hong Kong big data to identify rare side effects from antipsychotic medications through cross-disciplinary collaboration. Photo by HKU Med
