ArticleClinical pharmacokinetics2021
Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation.
Article in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Meta-analyses of clozapine, norclozapine levels and their ratio across three genome wide association studies.Translational psychiatry · 2025Pooled it
- Clozapine once- versus multiple-daily dosing: a two-center cross-sectional study, systematic review and meta-analysis.European archives of psychiatry and clinical neuroscience · 2023Pooled it
- Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.Schizophrenia bulletin · 2023Guideline
- A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia.CNS drugs · 2022Guideline
- CYP2D6 Genotypes Do Not Affect Clozapine Levels in a Large, Multicenter Cohort: Time Has Come to Revise Food and Drug Administration's Clozapine Packet Insert.Schizophrenia bulletin · 2026Article
- Higher risk of gastrointestinal stenosis and obstruction in clozapine-treated individuals with schizophrenia: a pharmacovigilance study based on the FDA adverse event reporting system database.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Rapid On-Demand Point-of-Care Monitoring of Clozapine and Its Metabolite Norclozapine Using Miniature Mass Spectrometry.Pharmaceuticals (Basel, Switzerland) · 2025Article
- A Call to Action for Starting Clozapine: Increasing Clozapine Use and Safety in a Post-REMS Era.Focus (American Psychiatric Publishing) · 2025Review
- Advocating for the inclusion of therapeutic drug monitoring in the national essential diagnostic list: Perspectives from psychiatrists.Indian journal of psychiatry · 2024Article
- Paralytic ileus in a patient on clozapine therapy showing an inverted clozapine/norclozapine ratio after switching valproic acid to carbamazepine: a case report.Therapeutic advances in psychopharmacology · 2024Article
- Oculogyric crisis symptoms related to risperidone treatment: a case report.BMC psychiatry · 2023Article
- Efficacy of sofpironium bromide gel on clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia: double-blind, controlled crossover study.BJPsych open · 2023Article
- Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.Pharmaceutics · 2022Review
- Nanochannel Array on Electrochemically Polarized Screen Printed Carbon Electrode for Rapid and Sensitive Electrochemical Determination of Clozapine in Human Whole Blood.Molecules (Basel, Switzerland) · 2022Article
- Observational
- Comment on: "Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation".Clinical pharmacokinetics · 2021Article
- Authors' Reply to Suhas et al.: Comment on: "Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation".Clinical pharmacokinetics · 2021Article
- 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
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveHypersalivation is a common, clozapine-related adverse drug reaction with a serious impact on quality of life. Pharmacokinetic correlates of clozapine-related hypersalivation have evaded attention. The purpose of this study was to compare pharmacokinetic parameters between clozapine-treated patients with vs. without hypersalivation from a large therapeutic drug monitoring database.
methodsOut of a large therapeutic drug monitoring dataset of clozapine-treated patients, we compared a group of patients with hypersalivation (n = 72) and a control group of patients without any adverse reactions in this regard (n = 323). Comparisons included plasma concentrations and concentrations-by-dose as well as demographic characteristics between groups. Post-hoc analyses were performed separately in smokers and non-smokers. We used the non-parametric Mann-Whitney U test and the chi-square test, while effects of confounders were assessed using a bootstrapping analysis of covariance.
resultsPatients with hypersalivation had higher clozapine plasma concentrations and concentrations-by-dose (p < 0.001 for the Mann-Whitney U test in both cases). Groups did not differ regarding demographic characteristics except for clozapine daily dose and percentage of smokers (p = 0.005 for the Mann-Whitney U test and p = 0.028 for the chi-square test, respectively). There were fewer smokers across patients with hypersalivation compared with patients without and daily doses were higher in patients with hypersalivation. After analysis of covariance, differences remained for both plasma concentrations and concentrations-by-dose (p < 0.001 for both). Post hoc analyses in smokers and non-smokers separately reported similar findings.
conclusionsElevated clozapine plasma concentrations and higher concentrations-by-dose were observed in patients with hypersalivation. A potential role for therapeutic drug monitoring in the prevention or management of clozapine-related hypersalivation is suggested.
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