SynthesisSchizophrenia research2012
When can patients with potentially life-threatening adverse effects be rechallenged with clozapine? A systematic review of the published literature.
Synthesis in Schizophrenia research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.Schizophrenia bulletin · 2023Guideline
- A Review of Clinical Advances and Challenges in Clozapine-Induced Myocarditis.Neuropsychiatric disease and treatment · 2025Review
- Clozapine-induced myocarditis and subsequent rechallenge: a narrative literature review and case report.Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent · 2023Article
- Myocarditis in patients on long-term antipsychotics -mechanism, management and recent updates.Heliyon · 2023Review
- Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia.Therapeutic advances in psychopharmacology · 2023Review
- Clozapine haematological monitoring for neutropenia: a global perspective.Epidemiology and psychiatric sciences · 2022Review
- Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital.Therapeutic advances in psychopharmacology · 2021Article
- Clozapine-Induced Pericardial Effusion Presenting with Persistent Tachycardia.Case reports in medicine · 2021Article
- Drug-Induced Idiosyncratic Agranulocytosis - Infrequent but Dangerous.Frontiers in pharmacology · 2021Review
- Clozapine-associated neutropenia following augmentation with sodium valproate.SAGE open medical case reports · 2021Article
- Clozapine Combination and Augmentation Strategies in Patients With Schizophrenia -Recommendations From an International Expert Survey Among the Treatment Response and Resistance in Psychosis (TRRIP) Working Group.Schizophrenia bulletin · 2020Article
- Isolated nausea and vomiting as the cardinal presenting symptoms of clozapine-induced myocarditis: a case report.BMC psychiatry · 2020Article
- Successful Clozapine Re-Challenge After Suspected Clozapine-Induced Myocarditis.The American journal of case reports · 2020Article
- Clozapine-induced agranulocytosis.Annals of hematology · 2020Review
- Neutrophil fluorescence in clozapine users is attributable to a 14kDa secretable protein.Pharmacology research & perspectives · 2020Article
- Protocol for Clozapine Rechallenge in a Case of Clozapine-Induced Myocarditis.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2020Article
- Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide.BMC psychiatry · 2020Review
- Genetic associations with clozapine-induced myocarditis in patients with schizophrenia.Translational psychiatry · 2020Article
- Incidence and Management of Clozapine-Induced Myocarditis in a Large Tertiary Hospital.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2019Article
- Successful clozapine rechallenge in a patient with suspected drug induced lupus.BMJ case reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundClozapine is widely prescribed for treatment refractory patients with schizophrenia, but its use is limited by potentially life threatening adverse effects. Rechallenge after these complications has been occasionally attempted in patients with severe psychotic symptoms.
objectiveTo review the outcome of clozapine rechallenge after potentially life threatening adverse effects.
methodsElectronic, all-language, literature search (1972-2011) followed by demographic and clinical data extraction. The outcome of rechallenge was considered favorable when the lower bound of the 95% confidence interval (CI) of the proportion of patients who could continue clozapine was >50%.
resultsAltogether, 138 patients (mean age: 36.3years, 65.7% male, 57.6% Caucasian, virtually all with schizophrenia spectrum diagnosis) underwent clozapine rechallenge after developing neutropenia (n=112), agranulocytosis (n=15), neuroleptic malignant syndrome (NMS) (n=5), myocarditis (n=4), pericarditis (n=1) and lupus erythematosus (n=1). Rechallenge strategies were heterogeneous and not systematically evaluated. Clozapine rechallenge was successful in 78/112 patients (69.6%, CI: 60.6-77.4) after neutropenia, 3/15 (20%, CI: 7.1-45.2) after agranulocytosis, 5/5 (100%, CI: 56-100) after NMS, 3/4 (75%, CI: 30-95) after myocarditis, 1/1 after pericarditis, and 0/1 after clozapine-induced lupus. Successfully rechallenged patients were followed for 16-96weeks. None of the rechallenged patients died.
conclusionsAlthough controlled studies are clearly needed, using a priori, confidence interval-based criteria, case reports/series suggest that in refractory patients who benefited from clozapine, careful rechallenge can be considered after neutropenia and NMS, but not after agranulocytosis and myocarditis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.