ArticlePharmacopsychiatry2014
Can valproic acid be an inducer of clozapine metabolism?
Article in Pharmacopsychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
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Who cites it
14 citing papers in PubMed, 58 citations in OpenAlex.
- The Effect of Body Weight Changes on Total Plasma Clozapine Concentrations Determined by Applying a Statistical Model to the Data From a Double-Blind Trial.Journal of clinical psychopharmacology · 2018Trial
- Impact of valproate co-medication and age on lurasidone exposure: a population pharmacokinetic study and real-world evaluation in Chinese psychiatric inpatients.Frontiers in pharmacology · 2026Article
- Comparison of clozapine doses and tolerability in patients with and without concurrent valproic acid.The mental health clinician · 2022Article
- Valproic acid autoinduction: a case-based review.International journal of bipolar disorders · 2021Review
- The Impact of Smoking, Sex, Infection, and Comedication Administration on Oral Olanzapine: A Population Pharmacokinetic Model in Chinese Psychiatric Patients.European journal of drug metabolism and pharmacokinetics · 2021Article
- Considerations of HLA, Renal Failure, Valproic Acid Use, and Current Treatment Guidelines in Clozapine-Induced Agranulocytosis.Case reports in psychiatry · 2021Article
- Measuring individual benefits of psychiatric treatment using longitudinal binary outcomes: Application to antipsychotic benefits in non-cannabis and cannabis users.Journal of biopharmaceutical statistics · 2020Article
- Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity.The pharmacogenomics journal · 2020Article
- Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine.Biosensors & bioelectronics · 2017Article
- Measuring the individual benefit of a medical or behavioral treatment using generalized linear mixed-effects models.Statistics in medicine · 2016Article
- The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.International journal of molecular sciences · 2016Review
- Three patients needing high doses of valproic Acid to get therapeutic concentrations.Case reports in psychiatry · 2015Article
- 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
- Do Asian Patients Require Only Half of the Clozapine Dose Prescribed for Caucasians? A Critical Overview.Indian journal of psychological medicineReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
introductionPrior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that (i) VPA is a net inducer of clozapine metabolism, and (ii) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study.
methodsAfter excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model.
resultsVPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14-39%) after controlling for confounding variables including smoking (35% lower, 28-56%). DISCUSSION: Prospective studies are needed to definitively establish that VPA may (i) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and (ii) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism.
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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.