Trial reportMolecular psychiatry2011
Genetic variation in CYP3A43 explains racial difference in olanzapine clearance.
Trial report in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
19 citing papers in PubMed, 67 citations in OpenAlex.
- Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features.Molecular psychiatry · 2024Trial
- Randomized, double-blind, 6-week non-inferiority study of lurasidone and risperidone for the treatment of schizophrenia.Psychiatry and clinical neurosciences · 2020Trial
- The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine: A Population Pharmacokinetic Analysis of the STOP-PD.Clinical pharmacokinetics · 2015Trial
- A rime-like Au-Pt nanostructured film and polyaniline-MIP based electrochemical sensor for olanzapine detection.Mikrochimica acta · 2026Article
- Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments.Pharmaceutics · 2024Review
- Samidorphan/olanzapine combination therapy for schizophrenia: Efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials.Annals of medicine and surgery (2012) · 2022Review
- 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
- CYP2D6 Genetic Variation and Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis.Frontiers in psychology · 2021Article
- Physiologically-Based Pharmacokinetic Modeling for Predicting Drug Interactions of a Combination of Olanzapine and Samidorphan.CPT: pharmacometrics & systems pharmacology · 2020Article
- How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?Frontiers in genetics · 2020Review
- A review of a recently published guidelines' "strong recommendation" for therapeutic drug monitoring of olanzapine, haloperidol, perphenazine, and fluphenazine.The mental health clinician · 2019Article
- Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations.Dialogues in clinical neuroscience · 2016Review
- Genetic variation in CYP3A43 is associated with response to antipsychotic medication.Journal of neural transmission (Vienna, Austria : 1996) · 2015Review
- Pharmacogenetics and outcome with antipsychotic drugs.Dialogues in clinical neuroscience · 2014Review
- Identification of candidate single-nucleotide polymorphisms in NRXN1 related to antipsychotic treatment response in patients with schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Pharmacogenetics of antipsychotics.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2014Review
- Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders.Pharmacogenomics and personalized medicine · 2014Review
- Influence of FMO1 and 3 polymorphisms on serum olanzapine and its N-oxide metabolite in psychiatric patients.The pharmacogenomics journal · 2013Article
- Sulfotransferase 4A1 Haplotype 1 (SULT4A1-1) Is Associated With Decreased Hospitalization Events in Antipsychotic-Treated Patients With Schizophrenia.The primary care companion for CNS disorders · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The antipsychotic drug, olanzapine, one of the most widely used drugs in clinical medicine, has a high rate of discontinuation due to inefficacy and/or adverse effects. We identified a single nucleotide polymorphism in the drug metabolizing enzyme, cytochrome P450 3A43 (CYP3A43; rs472660), that highly significantly predicted olanzapine clearance in the Clinical Antipsychotic Trials of Intervention Effectiveness trial (P=5.9e(-7)). Moreover, at standard antipsychotic doses, 50% of individuals with the high clearance genotype (AA) have trough blood levels below the therapeutic range. Interestingly, a much higher proportion of African Americans carry the A allele compared with Caucasians (allele frequency 67 vs 14%). After accounting for CYP3A43 genotype, race is no longer a significant predictor of olanzapine clearance. Olanzapine clearance was associated with measures of clinical response. Patients with greater clearance had higher symptom ratings and were more likely to discontinue treatment due to an inadequate response. Our data identify a genetic mechanism for variation in olanzapine response and demonstrate that blood level monitoring of olanzapine treatment is advisable.
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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.