Evidence map›Paper›PMID 26481172›Full record

Trial reportThe American journal of psychiatry2016

Differential Response to Risperidone in Schizophrenia Patients by KCNH2 Genotype and Drug Metabolizer Status.

Juliane Heide, Fengyu Zhang, Kristin L Bigos, Stefan A Mann, Vaughan J Carr, Cynthia Shannon Weickert, Melissa J Green, Daniel R Weinberger, Jamie I Vandenberg

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The American journal of psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Analysis ofGenes · 2022
    Article
  5. Review
  6. The ERG1 KFrontiers in molecular neuroscience · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Association Study ofFrontiers in psychiatry · 2019
    Article
  11. Alternative splicing isoforms in health and disease.Pflugers Archiv : European journal of physiology · 2018
    Review
  12. Article
  13. Inhibition of cloned hERG potassium channels by risperidone and paliperidone.Naunyn-Schmiedeberg's archives of pharmacology · 2017
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Juliane HeideFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Fengyu ZhangFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Kristin L BigosFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Stefan A MannFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Vaughan J CarrFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Cynthia Shannon WeickertFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Melissa J GreenFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Daniel R WeinbergerFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
Jamie I VandenbergFrom the Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, University of New South Wales, Darlinghurst; the Schizophrenia Research Institute, Darlinghurst; the Lieber Institute for Brain Development, Baltimore; the Department of Psychiatry and Behavioral Sciences, the Department of Neurology, the Department of Neuroscience, the Institute of Genetic Medicine, and the Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore; the School of Psychiatry, University of New South Wales, Randwick; the Research Unit for Schizophrenia Epidemiology, University of New South Wales, Darlinghurst; and Neuroscience Research Australia, Randwick.
UNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveAntipsychotic drugs target dopamine and serotonin receptors as well as Kv11.1 potassium channels encoded by KCNH2. Variable patient responses and a wide range of side effects, however, limit their efficacy. Slow metabolizer status and gene variants in KCNH2 associated with increased expression of Kv11.1-3.1, an alternatively spliced isoform of Kv11.1, are correlated with improved responses to antipsychotic medications. Here, the authors test the hypothesis that these effects may be influenced by differential drug binding to Kv11.1 channel isoforms.

methodDrug block of Kv11.1 isoforms was tested in cellular electrophysiology assays. The effects of drug metabolism and KCNH2 genotypes on clinical responses were assessed in patients enrolled in the multicenter Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

resultsRisperidone caused greater in vitro block of the alternatively spliced Kv11.1-3.1 isoform than full-length Kv11.1-1A channels, whereas its metabolite paliperidone and other atypical antipsychotics have similar potencies for the two isoforms. In the CATIE study (N=362), patients with genotypes associated with increased Kv11.1-3.1 expression (N=52) showed a better treatment response to risperidone compared with other drugs, but this association was dependent on metabolism status. Patients with KCNH2 risk genotypes and slow metabolizer status (approximately 7% of patients) showed marked improvement in symptoms when treated with risperidone compared with patients with fast metabolizer status or without the KCNH2 risk genotypes.

conclusionsThese data support the hypothesis that Kv11.1 channels play a role in the therapeutic action of antipsychotic drugs, particularly risperidone, and further highlight the promise of optimizing response with genotype-guided therapy for schizophrenia patients.

Indexed as

RisperidoneSchizophreniaAdultAlternative SplicingAntipsychotic AgentsERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsFemaleGenotypeHumansMaleProtein IsoformsTreatment OutcomeAntipsychotic AgentsERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsKCNH2 protein, humanProtein IsoformsRisperidone

Identifiers

PMID26481172
OpenAlexW2108403804

What OpenQuestion holds

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Registered trials

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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.