ArticlePsychiatry investigation2021
Clozapine Is Better Tolerated in Younger Patients: Risk Factors for Discontinuation from a Nationwide Database in Japan.
Article in Psychiatry investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Risk factors associated with blood dyscrasia during clozapine treatment: a systematic review and meta-analysis.Psychological medicine · 2026Pooled it
- Association between initial 30-day cumulative clozapine dose and risk of agranulocytosis: A nationwide register-based cohort study.Psychiatry and clinical neurosciences · 2026Article
- Clozapine-Associated Neutropenia among People on Clozapine in Japan: A Nationally Representative Retrospective Cohort Study.Schizophrenia bulletin · 2026Article
- Associations between clozapine availability, the diagnosis of treatment-resistant schizophrenia subgroups, antipsychotic monotherapy, and concomitant psychotropics among patients with schizophrenia: a real-world nationwide study.The international journal of neuropsychopharmacology · 2025Article
- Data Mining for Risks of Clozapine Side Effects, Including Neutropenia, Associated with Lithium Carbonate Administration: Analysis Using the Japanese Adverse Drug Event Report Database.Drugs - real world outcomes · 2023Article
- Dropout rates and reasons for dropout among patients receiving clozapine.Indian journal of psychiatry · 2023Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe effectiveness of clozapine is clearly superior to other antipsychotics in the treatment of refractory schizophrenia. Clozapine leads to various side effects, and therefore many patients are forced to discontinue. In this study, we analyzed the registry database of all cases in Japan to identify risk factors for discontinuation of clozapine.
methodsThe Clozaril patient monitoring service® (CPMS) database from July 31, 2009 to January 26, 2020 was acquired. We defined the following exclusion criteria: patients who had ever taken clozapine by a non-CPMS method, such as an individual import or clinical trial, patients who did not receive clozapine after being enrolled in CPMS, and patients with initial doses other than 12.5 mg (outside the current protocol). Therefore, all patients in this study are new users. Multivariate Cox regression analysis was used to investigate independent risk factors associated with time to discontinuation of clozapine.
resultsWe identified 8,263 patients as the study population. Clozapine discontinuation was significantly associated with age 40 and older [hazard ratio (HR)=1.66, p<0.001], intolerance to olanzapine (HR=1.31, p=0.018), previous treatment with clozapine (HR=1.30, p=0.001), and leukocyte counts <6,000/mm3 (HR=1.24, p<0.001). The Kaplan-Meier curves for clozapine discontinuation by age group revealed that older age at the time of clozapine introduction tended to have lower continuation rates.
conclusionCareful administration is important because patients with these factors have a high risk of discontinuation. In addition, the initiation of clozapine during the younger period was more effective and more tolerated.
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