ArticleEuropean journal of drug metabolism and pharmacokinetics2026
The Impact of Fluvoxamine on Clozapine and Norclozapine Serum Concentrations.
Article in European journal of drug metabolism and pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveFluvoxamine, a potent CYP1A2 inhibitor, increases clozapine serum concentrations by inhibiting its N-dealkylation to norclozapine, thus reducing norclozapine formation and increasing the clozapine/norclozapine ratio. Clinically, fluvoxamine may reduce clozapine tablet burden and mitigate norclozapine-related metabolic side-effects. However, clinical guidance on this co-administration is limited. The current study evaluates the effect of fluvoxamine and its dose on clozapine and norclozapine concentrations and their ratio, while exploring potential influencing factors.
methodsPatients from long-stay psychiatric wards were included if they had been or were currently receiving clozapine and fluvoxamine, with available steady-state concentrations with and without fluvoxamine coadministraton. Dose-adjusted clozapine and norclozapine concentrations (C/D, ng/mL per mg/day) and their ratios were compared among the two conditions using the Wilcoxon signed-rank test. Median fold increases and associations with clinical variables (e.g. gender, smoking, dosing frequency, baseline clozapine level, fluvoxamine dose), were analysed using Mann-Whitney U tests.
resultsSixty-seven patients were included. During fluvoxamine co-administration, median C/D clozapine increased from 0.70 to 1.72, C/D norclozapine from 0.43 to 0.80 and the clozapine/norclozapine ratio from 1.66 to 2.16 (all p < 0.001). Median fold increases were 2.51 (clozapine), 1.92 (norclozapine) and 1.27 (clozapine/norclozapine ratio). Greater increases were observed with fluvoxamine doses > 25 mg and baseline clozapine levels < 350 ng/mL, without a significant increase in clozapine/norclozapine ratio. Other factors showed no significant association.
conclusionFluvoxamine significantly increases clozapine and norclozapine concentrations, and their ratio. Doses > 25 mg lead to greater fold increases and more variability. Initiation at 25 mg with a 50% clozapine dose reduction is recommended.
Indexed as
Identifiers
What OpenQuestion holds
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.