ReviewPharmaceuticals (Basel, Switzerland)2022
Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.
Review in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
19 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Meta-analyses of clozapine, norclozapine levels and their ratio across three genome wide association studies.Translational psychiatry · 2025Pooled it
- Association Between Clozapine Plasma Concentrations and Treatment Response: A Systematic Review, Meta-analysis and Individual Participant Data Meta-analysis.Clinical pharmacokinetics · 2023Pooled it
- Late-Onset Neutropenia in Clozapine Users: Unrelated or Drug-Induced? A Case-Registry Analysis of Incidence, Characteristics, and Rechallenge Attempts.Schizophrenia bulletin · 2026Article
- Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation.Molecules (Basel, Switzerland) · 2026Article
- Clozapine-Associated Generalized Seizure at Therapeutic Dose Without Prior Epilepsy: A Case Report.Clinical medicine insights. Case reports · 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
- 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
- Forensic considerations in cases of fatal constipation.Forensic science, medicine, and pathology · 2025Review
- Comparing the Metabolic, Systemic, and Neuropsychiatric Impacts of Olanzapine and Clozapine in Patients with Schizophrenia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Clozapine-associated adverse drug reactions in 38,349 psychiatric inpatients: drug surveillance data from the AMSP project between 1993 and 2016.Journal of neural transmission (Vienna, Austria : 1996) · 2024Observational
- Evidence for the Role of the Mitochondrial ABC Transporter MDL1 in the Uptake of Clozapine and Related Molecules into the YeastPharmaceuticals (Basel, Switzerland) · 2024Article
- Recurrent high creatine kinase levels under clozapine treatment - a case report assessing a suspected adverse drug reaction.Frontiers in psychiatry · 2024Article
- Mediation and longitudinal analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count.Schizophrenia (Heidelberg, Germany) · 2023Article
- Analysis of clozapine-induced seizures using the Japanese Adverse Drug Event Report database.PloS one · 2023Article
- Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia.Therapeutic advances in psychopharmacology · 2023Review
- Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.Pharmaceutics · 2022Review
- Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part II: A Review of Fatal Outcomes in US Pharmacovigilance Data and Proposed Changes.Journal of clinical psychopharmacologyArticle
- 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
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.
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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.