Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Clozapine Use and Risk of Infections in Patients with Schizophrenia: A Population-Based Cohort Study
29 Pages Posted: 26 Apr 2025
More...Abstract
Background: Infection is the leading natural cause of mortality in patients with schizophrenia and antipsychotic use may be associated with an increased risk of infections. This study aims to examine the association of clozapine use with a wide variety of infectious diseases.
Methods: This population-based cohort study utilized territory-wide electronic health records from the Hong Kong Hospital Authority. We included individuals aged 18 years or older with a diagnosis of schizophrenia (ICD-9-CM code 295) from January 1st, 2002, to December 31st, 2023. Patients who used clozapine or olanzapine continuously for at least 90 days were included; olanzapine was chosen as a comparator due to its similar chemical structure and mechanism. The primary outcome was the occurrence of any infectious disease, with subtypes analyzed as secondary outcomes.
Findings: Among 8,612 patients (612 clozapine users and 8,000 olanzapine users), clozapine users had a 27% higher overall infection risk compared to olanzapine users (hazard ratio [HR]= 1.27, 95% confidence interval [CI]: 1.08-1.49). The absolute rate of infectious diseases was 1,100.37 per 100,000 person-years higher in clozapine users compared to olanzapine users (95% CI: 173.55-2,134.98). The risk was notably higher in older individuals, with adjusted HRs rising from 1.29 (95% CI: 1.03,1.61) in the aged 18-44 years to 1.58 (95% CI: 1.23-2.03) among aged 45-64 years and 2.17 (95% CI: 1.42-3.31) for those aged 65 years or older. The absolute rate differences were 3,408.36 per 100,000 person-years (95% CI: 1,359.31-5,815.03) for those aged 45-64 years and 10,345.97 per 100,000 person-years (95% CI: 1681.96-20851.76) for those aged 65 years or older. Secondary analyses identified upper and lower respiratory tract infections as primary contributors to the observed association.
Interpretation: Clozapine use is associated with a significantly higher risk of infectious diseases, particularly respiratory tract infections, compared to olanzapine. The risk is more markedly pronounced in older adults. Clinicians should balance the therapeutic benefits of clozapine with infection control measures, including regular monitoring and preventive strategies.
Keywords: Clozapine, schizophrenia, antipsychotics, treatment resistance, respiratory infection
Suggested Citation: Suggested Citation