Observational studyCNS drugs2021
Absolute and Dose-Adjusted Serum Concentrations of Clozapine in Patients Switching vs. Maintaining Treatment: An Observational Study of 1979 Patients.
Observational study in CNS drugs, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed.
- Effects of smoking cessation on plasma clozapine concentrations in male patients with schizophrenia during the COVID-19 pandemic.Frontiers in psychiatry · 2023Article
- Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.Pharmaceutics · 2022Review
- Metabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment: A Retrospective Pilot Study.Journal of clinical psychopharmacologyArticle
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundClozapine is an effective drug for the management of schizophrenia that has not responded to other agents, but some patients experience insufficient or adverse effects and discontinue treatment.
objectiveWe investigated a potential association between clozapine serum concentrations and switching to other antipsychotics in a large real-world patient population from a therapeutic drug monitoring service.
methodsAbsolute and dose-adjusted serum concentrations (concentration-to-dose ratios [C/D ratios]) of clozapine during dosing between 100 and 1000 mg/day were measured in 1979 Norwegian patients during the period 2005-2019. These variables were compared in patients switching to other antipsychotic drugs versus maintaining clozapine treatment using linear mixed models. Smoking habits were known for 49% of the patients. To prevent potential nonadherence affecting clozapine switching, only patients with serum concentrations above 50% of the lower reference range were included.
resultsIn total, 190 patients (9.6%) switched from clozapine to another antipsychotic drug during the study period, whereas the remaining patients were not detected as switchers and were interpreted as maintaining treatment. Patients switching treatment had 23.5% lower absolute concentrations (954 vs. 1245 nmol/L; p < 0.001) and 15.7% lower daily doses (305 vs. 362 mg/day; p < 0.001) of clozapine than did nonswitchers, making the clozapine C/D ratio 9.7% lower in switchers than in nonswitchers after correcting for smoking habits (2.80 vs. 3.10 nmol/L/mg/day; p = 0.032).
conclusionsThe present study suggests that decreased absolute and dose-adjusted serum concentrations of clozapine were associated with clozapine discontinuation. The significantly reduced clozapine concentrations regardless of prescribed dose in switchers versus nonswitchers may indicate a pharmacokinetic mechanism underlying the risk of clozapine discontinuation.
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Registered trials
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