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TOPLINE:

Clozapine use was associated with a 25% higher risk for infections in patients with schizophrenia than the use of olanzapine, with a 45% higher risk in those aged 55 years or older, a large cohort study showed.

METHODOLOGY:

• The population-based cohort study included electronic health record data from the Hong Kong Hospital Authority for more than 11,051 adults with schizophrenia.
• Participants had used clozapine (n = 1450; mean age, 41 years; 52% women) or olanzapine (n = 9601; mean age, 45 years; 55% women) continuously for 90 or more days and had previously used at least two other antipsychotic medications, representing a cohort with treatment resistance.
• The primary outcome was occurrence of any infectious disease, with subtypes analyzed as secondary outcomes.
• Medication was initiated from 2004 to 2023, with 2002-2003 as a wash-out period. Mean follow-up periods for clozapine and olanzapine users were about 6.9 years and 5 years, respectively.

TAKEAWAY:

• Overall, 3551 cases of infections were observed during the study. Clozapine use was associated with a significantly greater risk for infection than olanzapine use (weighted hazard ratio [HR], 1.25; P < .0001).
• Risk for infection from use of clozapine vs olanzapine increased with age: 18-44 years (weighted HR, 1.24; P = .002), 44-54 years (weighted HR, 1.41; P = .001), and 55 years or older (weighted HR, 1.45; P = .002).
• Risk for upper and lower respiratory tract infections was also significantly higher with use of clozapine vs olanzapine (weighted HRs, 1.50 and 1.71, respectively; P < .0001 for both) as was the risk for gastrointestinal infections (weighted HR, 1.90; P = .0001).
• Although men and women both had significantly greater infection risk with use of clozapine vs olanzapine, the rate was greater in men (weighted HRs, 1.32 and 1.18, respectively).

IN PRACTICE:

The investigators noted that although there have been calls to relax current requirements for regular hematological monitoring when using clozapine, their findings “underscore the importance of regular follow-up to identify early and manage infections, which possibly arise because of a weakened immune system.”

Authors of an accompanying editorial noted that patients receiving higher doses might be at even greater risk for adverse events.

“An intermediate balance of personalized dosing designed to limit clozapine-induced inflammation and regular blood testing and physical monitoring…could offer a safe and less invasive compromise to maximize the number of patients receiving clozapine treatment,” the editorial authors wrote.

SOURCE:

The study was led by Yuqi Hu, MSc, the University of Hong Kong, Hong Kong. The editorial was led by Scott R. Clark, PhD, University of Adelaide, Adelaide, Australia. Both were published online on July 28 in The Lancet Psychiatry.

LIMITATIONS:

The study was limited by its observational design, which may have introduced selection bias, and by the absence of key covariates, including socioeconomic status and lifestyle factors. It also lacked laboratory data on drug levels and immune function and only captured infections requiring secondary or tertiary care. Additional constraints included unmeasured anticholinergic effects, a predominantly Chinese cohort that limited generalizability, and not including patients with lived experience.

DISCLOSURES:

The study was partially supported by the Laboratory of Data Discovery for Health funded by AIR@InnoHK. Some of the study investigators and editorialists reported having financial, advisory, or employment ties with various sources, including pharmaceutical companies. Full details are provided in the original articles.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.