SynthesisThe British journal of psychiatry : the journal of mental science2023
Optimising plasma clozapine levels to improve treatment response: an individual patient data meta-analysis and receiver operating characteristic curve analysis.
Synthesis in The British journal of psychiatry : the journal of mental science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Vaccination and clozapine use: a systematic review and an analysis of the VAERS database.European archives of psychiatry and clinical neuroscience · 2025Pooled it
- Utility of clozapine trough level reporting in clinical practice: A four-year retrospective evaluation from India.Indian journal of psychiatry · 2026Article
- Clozapine Dose Reduction in Remitted Patients With Treatment-Resistant Schizophrenia: A Case Series.Schizophrenia bulletin · 2026Article
- The distinct effects of metabolic syndrome on negative symptoms and on antipsychotic therapy of schizophrenia involve insular volume, functional connectivity, and genetic polymorphisms.Translational psychiatry · 2026Article
- Pharmacological treatment of schizophrenia: Japanese Expert Consensus 2025.Schizophrenia (Heidelberg, Germany) · 2026Article
- Real-world comprehensive care of people living with schizophrenia: recommendations across different settings and clinical stages.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026Article
- Longitudinal trends in blood concentrations of clozapine and norclozapine, inflammatory markers, and clinical outcomes in Japanese patients: a 12-week prospective study.Frontiers in psychiatry · 2026Article
- A Case of Clozapine Toxicity Caused by Infection in a Patient with Treatment-Resistant Schizophrenia.International medical case reports journal · 2026Article
- Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia.Journal of clinical medicine · 2025Article
- Effectiveness of clozapine augmentation with specific doses of other antipsychotics in schizophrenia: a meta-analysis from two nationwide cohorts.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2025Article
- Clozapine plasma level toxicity induced by a pharmacokinetic interaction with bupropion: A case report.The mental health clinician · 2025Article
- Managing ciprofloxacin-clozapine interaction with immunoassay-based monitoring: A case report.The mental health clinician · 2025Article
- Efficacy and tolerability of pharmacological interventions for schizophrenia non-responsive to prior treatment: a systematic review and network meta-analysis.EClinicalMedicine · 2025Article
- Deep Learning-Assisted SERS for Therapeutic Drug Monitoring of Clozapine in Serum on Plasmonic Metasurfaces.Nano letters · 2025Article
- Evaluating the Role of Clozapine in Treatment-Resistant Schizophrenia: A Narrative Synthesis of Clinical, Economic, and Quality-of-Life Outcomes.Neuropsychiatric disease and treatment · 2025Review
- Impact of patient-specific factors on clozapine metabolism in individuals with treatment-resistant schizophrenia or schizoaffective disorder.Journal of psychopharmacology (Oxford, England) · 2024Article
- [Management of treatment resistance-Treatment-resistant schizophrenia].Der Nervenarzt · 2024Review
- Article
- Clozapine but not lithium reverses aberrant tyrosine uptake in patients with bipolar disorder.Psychopharmacology · 2023Article
- Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I: A Review of the Pharmacokinetic Literature and Proposed Changes.Journal of clinical psychopharmacologyReview
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response.
aimsUsing individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice.
methodWe conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response.
resultsWe included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223-558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine.
conclusionsClozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.
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