SynthesisClinical pharmacokinetics2023
Association Between Clozapine Plasma Concentrations and Treatment Response: A Systematic Review, Meta-analysis and Individual Participant Data Meta-analysis.
Synthesis in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Effect of Alternative Administrations on P2Y12 Receptor Inhibitors' Pharmacokinetics and Pharmacodynamics: Systematic Review and Meta-Analysis.The AAPS journal · 2025Pooled it
- Advancing Personalized Medicine in Psychiatry: A Descriptive Pilot Study Integrating Pharmacogenetics and Pharmacokinetics in Long-Acting Antipsychotic Treatment.Pharmaceutics · 2026Article
- Clozapine levels in inpatients with schizophrenia are not a predictor of rehospitalization: a naturalistic retrospective study.Pharmacological reports : PR · 2026Article
- Article
- A Call to Action for Starting Clozapine: Increasing Clozapine Use and Safety in a Post-REMS Era.Focus (American Psychiatric Publishing) · 2025Review
- Exploratory analysis of non-linear clozapine dose-concentration relationship in real-life hospital database.Frontiers in pharmacology · 2025Article
- [Management of treatment resistance-Treatment-resistant schizophrenia].Der Nervenarzt · 2024Review
- 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesAlthough therapeutic drug monitoring of clozapine is recommended, its optimisation is often adjusted only on the basis of dosage. The aim of this study was to assess the link between clozapine plasma concentrations and clinical response by a meta-analysis of published studies and by an individual participant data meta-analysis.
methodsWe conducted a computerised search of bibliographic databases (EMBASE, PubMed, Clinical Trials, and Web of Science) to identify studies that assessed the relationship between clozapine serum or plasma concentrations and clinical efficacy. Using pooled data, we investigated the association between improvement of clinical outcome and clozapine or norclozapine plasma concentrations, the sum of clozapine and norclozapine plasma concentrations, and the coefficient of variation of clozapine plasma concentrations. Using available individual data, we assessed the relationship between clozapine plasma concentrations and clinical response (changes in the Brief Psychiatric Rating Scale score) and identified a threshold level for a favourable clinical response.
resultsFifteen studies satisfied inclusion criteria. Our meta-analysis showed that responders had clozapine plasma concentrations that were, on average, 117 ng/mL higher than non-responders. The patients with plasma clozapine concentrations above the thresholds identified in each study had a higher likelihood of responding (odds ratio = 2.94, p < 0.001). Norclozapine plasma concentrations were not associated with a clinical response. The meta-analysis of individual data supported this result and confirmed the link between clozapine concentrations and a change in the Brief Psychiatric Rating Scale score and/or the probability of clinical response. Finally, with the analysis of the coefficient of variation of clozapine plasma concentrations, we found that a greater inter-individual fluctuation in plasma concentrations was associated with a loss of clinical response.
conclusionsOur work confirmed that, in contrast to clozapine doses, clozapine plasma concentrations were related to a favourable clinical response, with a mean difference between responders and non-responders of 117 ng/mL. A threshold for a treatment response of 407 ng/mL was determined, with a high discriminatory capacity, and a sensitivity and specificity of 71% and 89.1%, respectively.
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