Continued treatment with clozapine has been associated with a lower the risk of suicide mortality among patients with schizophrenia in Hong Kong, according to a study.
In a population-based cohort study of schizophrenia patients followed over a median of 12.37 years, clozapine use reduced the rate of suicide mortality by 27-percent compared with non-clozapine antipsychotic use (incident rate ratio, 0.73, 95 percent confidence interval [CI], 0.55–0.98). [Br J Psychiatry 2026;229:140-148]
When antipsychotic use was evaluated by continuity, continued clozapine use (ie, active clozapine prescription for >90 percent of the total follow-up period) was associated with prolonged survival time for suicide mortality compared with continued use of other antipsychotics (acceleration factor, 3.01, 99 percent CI, 1.41–6.44; p<0.001).
Furthermore, continued use of clozapine in addition to another antipsychotic drug was linked to longer survival time for both suicide mortality (acceleration factor, 3.67, 99 percent CI, 1.41–9.60; p=0.0024) and all-cause mortality (acceleration factor, 1.42, 99 percent CI, 1.07–1.88; p=0.0067) compared with continued use of other antipsychotics.
No significant associations were observed between continued clozapine use and mortality related to cardiovascular disease, cancer, or infectious diseases.
“These findings, which demonstrate association rather than causality, strengthen the evidence base supporting clozapine’s value beyond symptom control, particularly where suicide risk is a clinical concern,” principal investigator Prof Sherry Chan from the University of Hong Kong, Hong Kong SAR, China, told MIMS in an email.
Chan also advised careful interpretation of the polypharmacy finding, saying that the study could not establish whether the lower all-cause and suicide mortality in the group of patients with continued clozapine treatment was caused by the continued use of another antipsychotic.
Sherry Chan, MBBS, MD, MPhil, FRCPsych, FHKCPsych, FHKAM
Assistant Dean, LKS Faculty of Medicine, Hong Kong University (HKU)
Clinical Professor at the Department of Psychiatry, School of Clinical Medicine, HKUPrioritizing safe, continued treatment
Overall, the present data offer reassurance about using clozapine for schizophrenia in appropriate candidates, according to Chan.
“Concerns about adverse effects should not cause therapeutic delay or premature discontinuation,” she said, “but this does not mean indiscriminate prescribing. In everyday practice, this requires a deliberate benefit–risk assessment for each patient.”
Chan emphasized that in making decisions about clozapine treatment, clinicians should weigh the potential benefits for treatment-resistant illness and suicide risk against the common adverse effects and rare serious reactions and the demands of monitoring. This involves considering treatment response, clinical risk, physical comorbidity, concomitant medications, smoking status, patient preferences, and capacity for follow-up, she added.
Ultimately, the priority is continued treatment, Chan said. “The mortality benefit [in the study cohort] was most evident in patients who maintained clozapine treatment. The task is therefore to select suitable patients carefully and then make ongoing treatment as safe and workable as possible.”
Several barriers, however, make continued clozapine treatment challenging for patients, Chan noted. “Blood monitoring, frequent visits, and dispensing can burden patients and families. Sedation, hypersalivation, constipation, and metabolic change can also reduce [the patients’] willingness to continue, while concerns about serious events is understandable.”
To overcome the said barriers, Chan urged clinicians to provide repeated education before and during treatment, as well as to involve family and other support networks to aid adherence. She also advocated for a structured pathway that integrates automated reminder systems, synchronized lab-to-pharmacy workflows, dedicated care coordinators, and active liaison between mental health, primary care, and pharmacy services.
As for monitoring clozapine safety, Chan emphasized the importance of individualized assessment but cautioned against relying on machine-learning prediction tools, which still require extensive validation. “For now, personalized risk management should continue to include systematic baseline assessment, careful titration, therapeutic drug monitoring where indicated, and prompt review when clinical status, infection risk, or medicines change,” she said.
The study included 9,456 patients (mean age at index date 39.13 years, 50.73 percent female) with schizophrenia who were treated at public hospitals in Hong Kong. Of these patients, 2,020 had continued clozapine use, 1,132 used clozapine but discontinued, 4,326 had continuous non-clozapine antipsychotic use, and 1,978 used a non-clozapine antipsychotic but discontinued. Clozapine users and users of other antipsychotic medications were matched based on propensity scores.
Among users of non-clozapine antipsychotic medications, olanzapine was the most frequently prescribed (69.88 percent), followed by haloperidol (54.86 percent).