ReviewPharmaceutics2021
Assessing the Mechanism of Fluoxetine-Mediated CYP2D6 Inhibition.
Review in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis 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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Deprescribing Antidepressants in Children and Adolescents: A Systematic Review of Discontinuation Approaches, Cross-Titration, and Withdrawal Symptoms.Journal of child and adolescent psychopharmacology · 2025Pooled it
- Elucidating the binding and metabolic interactions of sunitinib and sorafenib with Cytochrome P450s CYP2U1 and CYP2D6.Molecular pharmacology · 2026Article
- Trajectories of Clozapine Concentrations in Women Across Menopausal Age.Schizophrenia bulletin · 2026Article
- Pharmacogenomics ofPharmaceutics · 2025Article
- Mechanism of intermittent dosing of fluoxetine in premenstrual dysphoric disorder.Archives of women's mental health · 2025Review
- Serotonin Syndrome Versus Neuroleptic Malignant Syndrome in a Pediatric Patient Receiving Fluoxetine and Haloperidol: A Case Report.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Fluoxetine HCl-Loaded Nanostructured Lipid Carriers for Nose-to-Brain Delivery: Optimization and Synergistic Role of Saffron Oil.Journal of molecular neuroscience : MN · 2025Article
- High-capacity adsorption of fluoxetine using olive-stone derived activated biochar: insights into efficiency and mechanism.RSC advances · 2025Article
- Association of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study.PLoS medicine · 2025Article
- Five-Year Trends in SSRI Consumption: A Precision Medicine Approach to Comparative Analysis Between Serbia and European Countries.Healthcare (Basel, Switzerland) · 2025Article
- 3D Hepatocyte Model with Composite Nanofibers That Reproduced Human In Vivo Drug Clearance Profiles.ACS pharmacology & translational science · 2025Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- The Assessment of the Safety Profile of Selective Serotonin Reuptake Inhibitors Versus Other Antidepressants: Drug-Drug Interaction Insights from EudraVigilance.Journal of clinical medicine · 2025Article
- Hyponatremia Associated with the Use of Common Antidepressants in the All of Us Research Program.Clinical pharmacology and therapeutics · 2025Observational
- Clinical effects of CYP2D6 phenoconversion in patients with psychosis.Journal of psychopharmacology (Oxford, England) · 2024Article
- Advancing Bioanalytical Method Validation: A Comprehensive ICH M10 Approach for Validating LC-MS/MS to Quantify Fluoxetine in Human Plasma and Its Application in Pharmacokinetic Studies.Molecules (Basel, Switzerland) · 2024Article
- From bench to bedside: the application of cannabidiol in glioma.Journal of translational medicine · 2024Review
- Potential Dextromethorphan-Induced Serotonin Syndrome Leading to Homicide and Suicide.Academic forensic pathology · 2024Article
- Case Report: Life-Threatening Fluoxetine-Linked Postoperative Bleeding Informed by Pharmacogenetic Evaluation.Drugs in R&D · 2024Article
- Pharmacokinetics and Pharmacodynamics: A Comprehensive Analysis of the Absorption, Distribution, Metabolism, and Excretion of Psychiatric Drugs.Pharmaceuticals (Basel, Switzerland) · 2024Review
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 at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoxetine is still one of the most widely used antidepressants in the world. The drug is extensively metabolized by several cytochrome P450 (CYP450) enzymes and subjected to a myriad of CYP450-mediated drug interactions. In a multidrug regimen, preemptive mitigation of drug-drug interactions requires knowledge of fluoxetine actions on these CYP450 enzymes. The major metabolic pathway of fluoxetine leading to the formation of its active metabolite, norfluoxetine, is mediated by CYP2D6. Fluoxetine and norfluoxetine are strong affinity substrates of CYP2D6 and can inhibit, potentially through various mechanisms, the metabolism of other sensitive CYP2D6 substrates. Remarkably, fluoxetine-mediated CYP2D6 inhibition subsides long after fluoxetine first passes through the liver and even remains long after the discontinuation of the drug. Herein, we review pharmacokinetic and pharmacogenetic information to help us understand the mechanisms underlying the prolonged inhibition of CYP2D6 following fluoxetine administration. We propose that long-term inhibition of CYP2D6 is likely a result of competitive inhibition. This is due to strong affinity binding of fluoxetine and norfluoxetine to the enzyme and unbound fluoxetine and norfluoxetine levels circulating in the blood for a long period of time because of their long elimination half-life. Additionally, we describe that fluoxetine is a CYP2C9 substrate and a mechanism-based inhibitor of CYP2C19.
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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.