Evidence map›Paper›PMID 25212749›Full record

Trial reportAlcohol (Fayetteville, N.Y.)2014

Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: exploratory findings.

George A Kenna, William H Zywiak, Robert M Swift, John E McGeary, James S Clifford, Jessica R Shoaff, Samuel Fricchione, Michael Brickley, Kayla Beaucage, Carolina L Haass-Koffler and 1 more

Open access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alcohol (Fayetteville, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Pharmacogenetics of alcohol use disorder treatments: an update.Expert opinion on drug metabolism & toxicology · 2019
    Review
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

George A KennaDepartment of Psychiatry and Human Behavior, Brown University, Providence, RI, USA; Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA. Electronic address: George_Kenna@Brown.edu.
William H ZywiakDepartment of Psychiatry and Human Behavior, Brown University, Providence, RI, USA; Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Decision Scientific Institute, Pacific Institute for Research and Evaluation, Pawtucket, RI, USA.
Robert M SwiftDepartment of Psychiatry and Human Behavior, Brown University, Providence, RI, USA; Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Providence VA Medical Center, Providence, RI, USA.
John E McGearyDepartment of Psychiatry and Human Behavior, Brown University, Providence, RI, USA; Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Providence VA Medical Center, Providence, RI, USA.
James S CliffordVirginia Commonwealth University, Richmond, VA, USA.
Jessica R ShoaffCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Samuel FricchioneCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Michael BrickleyCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Kayla BeaucageCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Carolina L Haass-KofflerCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Lorenzo LeggioCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Brown University · USProvidence VA Medical Center · USNational Institutes of Health · USPacific Institute For Research and Evaluation · USVirginia Commonwealth University · US

Funding

Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN)ZIAAA000218 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI LEGGIO, LORENZO · 2013 to 2020
$22.8M
Matching 5-HT Genotypes to Serotonergic Medications for AlcoholismR01AA016079 · NIAAA · BROWN UNIVERSITY · PI KENNA, GEORGE A. · 2007 to 2010
$1.5M
Brown University Shared DNA SequencerS10RR023457 · NCRR · BROWN UNIVERSITY · PI MCGEARY, JOHN E · 2008 to 2008
$147k
NCRR NIH HHS 1S10RR023457-01A1NCRR NIH HHS S10 RR023457NIAAA NIH HHS R01 AA016079NIAAA NIH HHS R01-AA016079
6 · The paper itself

Abstract

The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200 mg/day of sertraline or 0.5 mg/day of ondansetron for 3 weeks followed by an alcohol self-administration experiment (ASAE), then placebo for 3 weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for 3 weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotype receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7 days prior to the first and third ASAEs than women receiving the mismatched medication (i.e., sertraline to LL and ondansetron to SS/SL). In a 3-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4≥7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4<7 repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad libitum during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be essential to successfully treat alcohol dependence.

Indexed as

Polymorphism, GeneticAdultAlcoholismDouble-Blind MethodFemaleGenotypeHumansMaleMiddle AgedOndansetronReceptors, Dopamine D4Serotonin Plasma Membrane Transport ProteinsSertralineDRD4 protein, humanOndansetronReceptors, Dopamine D4Serotonin Plasma Membrane Transport ProteinsSertralineSLC6A4 protein, human5-HTTLPRAlcoholDRD4GenderOndansetronSertraline

Identifiers

PMID25212749
PMCPMC4163011
OpenAlexW2018574373

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.