Observational studyCNS drugs2017
Correlation Between Serum Concentrations of N-Desmethylclozapine and Granulocyte Levels in Patients with Schizophrenia: A Retrospective Observational Study.
Observational study in CNS drugs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions.Psychopharmacology · 2021Pooled it
- Modulatory effects of valproic acid and UGT polymorphisms on norclozapine plasma levels in clozapine-treated patients with schizophrenia.Scientific reports · 2026Article
- Impact of the transcription factor nuclear factor 1 B T>C polymorphism on clozapine metabolism in vivo and expression of intestinal transporters in vitro.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Impact ofTherapeutic advances in psychopharmacology · 2025Article
- Advocating for the inclusion of therapeutic drug monitoring in the national essential diagnostic list: Perspectives from psychiatrists.Indian journal of psychiatry · 2024Article
- Association of clozapine and norclozapine levels with patient and therapy characteristics-focus on interaction with valproic acid.European journal of clinical pharmacology · 2023Article
- Mediation and longitudinal analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count.Schizophrenia (Heidelberg, Germany) · 2023Article
- Pharmacometric modeling of drug adverse effects: an application of mixture models in schizophrenia spectrum disorder patients treated with clozapine.Journal of pharmacokinetics and pharmacodynamics · 2023Article
- Impact of NFIB and CYP1A variants on clozapine serum concentration-A retrospective naturalistic cohort study on 526 patients with known smoking habits.Clinical and translational science · 2023Article
- Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.Pharmaceutics · 2022Review
- Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Observational
- Clozapine Metabolism is Associated With Absolute Neutrophil Count in Individuals With Treatment-Resistant Schizophrenia.Frontiers in pharmacology · 2021Article
- Clozapine and desmethylclozapine: correlation with neutrophils and leucocytes counting in Mexican patients with schizophrenia.BMC psychiatry · 2019Article
- Metabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment: A Retrospective Pilot Study.Journal of clinical psychopharmacologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundClozapine is restricted to use in patients with treatment-refractory schizophrenia due to the risk of a serious drop in absolute neutrophil granulocyte count (ANC). The formation of reactive, unstable metabolites (adducts) has been suggested as a mechanism of clozapine-induced granulocyte decline. These adducts are not detectable in vivo, but stable clozapine metabolites could potentially be indirect pharmacokinetic measures of adduct formation.
objectiveThe present retrospective observational study investigated the correlation between concentrations of N-desmethylclozapine, the major stable clozapine metabolite, and ANC in a real-life population of clozapine-treated patients.
methodsPatients were included from a therapeutic drug monitoring service at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway, between March 2005 and December 2015. Information about clozapine and N-desmethylclozapine steady-state trough concentrations, as well as accompanying measurements of ANC, were collected from the laboratory database. Correlations of serum concentrations of N-desmethylclozapine and clozapine (and their respective ratios) with ANC were investigated by linear mixed-model analysis.
resultsOverall, 129 patients with 855 measurements of clozapine/N-desmethylclozapine concentrations and ANC (range 0.9-19 × 10
conclusionsN-Desmethylclozapine level and ANC significantly correlated in this real-life population of schizophrenia patients. The positive correlation, which was also present for the metabolic ratio, might reflect reduced clozapine availability for the formation of reactive metabolites potentially affecting granulocyte level. However, as our findings were based on ANC mainly within the reference range, this hypothesis should be studied further in clozapine-treated patients with neutropenia or agranulocytosis.
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