Research Projects
The long-term impact of clozapine on mortality, hospitalization and comorbidity in patients with schizophrenia: a population-based registry study

About 15-30% of patients with schizophrenia do not respond to standard antipsychotic treatment and are considered as treatment resistant schizophrenia (TRS). Clozapine is the only antipsychotic medication that has shown to be effective in TRS patients, significantly superior to the other antipsychotic medications.  Clozapine has also been shown to be effective in reducing suicidality in patients with schizophrenia. On the other hand, patients with schizophrenia have an average life expectancy 20 years shorter than the general population and one of the key attributing factors is elevated rates of chronic physical conditions such as cardiometabolic disease. Among all the atypical antipsychotics, clozapine has been associated with the highest risk for developing metabolic complications. Therefore, it is crucial to have a comprehensive understanding of the long-term impact of clozapine use on mortality, comorbidity and hospitalization to better inform the benefit-risk of clozapine use. With the comprehensive clinical information recorded by the Clinical Data Analysis and Reporting System (CDARS) maintained by the Hospital Authority of Hong Kong, which is responsible for over 80% of psychiatric in Hong Kong, we propose to explore the long-term impact of clozapine use on mortality, hospitalization and comorbidity in patients with schizophrenia-spectrum disorders. Patients who first initiation of clozapine with the diagnosis of schizophrenia-spectrum disorders between year 2003 to 2012 will be identified as the clozapine group (ClozG). Patients with schizophrenia-spectrum disorders who were dispensed with any antipsychotic medications other than clozapine during year 2003 to 2012 and has never been exposed to clozapine before 2012 are considered as the non-clozapine group (nClozG). Base on the pilot study, the estimated number of ClozG patients is 2700 and that of the nClozG patients is 41276. The mortality information between year 2003 till 2022, information of hospitalization and comorbidities during the whole treatment period of ClozG and nClozG will be obtained from the CDARS. Age, gender, age of first diagnosis of schizophrenia-spectrum disorders and duration of illness will be used as covariates in all statistical analysis. Multivariable Cox proportional hazards regression analysis with propensity score weighing will be employed to compare mortality between ClozG and nClozG. Regression analysis will be used for exploring the hospitalization and comorbidities. Adapted Charlson comorbidity index will be used to explore the effect of prior comorbidity on the outcomes of clozapine use. Results of current study provide the long-term risk-benefit understanding of clozapine use and inform treatment guideline development of patients with schizophrenia.  

Professor Sherry Kit Wa Chan, Department of Psychiatry

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kwsherry@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.