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The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.

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

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Kenna, George A., Zywiak, William H., Swift, Robert M., McGeary, John E., Clifford, James S., Shoaff, Jessica R., Fricchione, Samuel, Brickley, Michael, Beaucage, Kayla, Haass-Koffler, Carolina L., Leggio, Lorenzo·2014·Alcohol
DOI 10.1016/j.alcohol.2014.04.005PMC PMC4163011
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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.

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  • A genetic variation in the serotonin 5-HT3 transporter (5-HTTLRP) influenced the effectiveness of ondansetron therapy.

    “The study revealed that a genetic variation in the serotonin 5-HT3 transporter (5-HTTLRP) influenced the effectiveness of ondansetron therapy”

    From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [70]

    The Results (Genotype effects; page unavailable) report an interaction between ondansetron response and 5-HTTLPR genotype in women, particularly alongside DRD4 genotype. The Introduction identifies 5-HTTLPR with the serotonin transporter and ondansetron as a 5-HT3 antagonist; the claim incorrectly calls 5-HTTLPR a variation in a “5-HT3 transporter” and omits the exploratory study’s population and DRD4 qualification. (LLM, conf=0.88)

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Research works printed but not linked: 1

  1. Watson, 1989, Total body water and blood alcohol levels: updating the fundamentals, Vol. 1, 41

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Metadata

Authors
Kenna, G. A., Zywiak, W. H., Swift, R. M., McGeary, J. E., Clifford, J. S., Shoaff, J. R., Fricchione, S., Brickley, M., Beaucage, K., Haass-Koffler, C. L., & Leggio, L.
Affiliations
  • Brown University (US)
  • Virginia Commonwealth University (US)
  • National Institutes of Health (US)
Corresponding author
Kenna, George A.
ORCID
Venue
Alcohol
Publisher
Elsevier BV
Published
2014-09
Volume
48
Issue
6
Pages
515-522
ISSN
0741-8329 (ISSN-L)
DOI
10.1016/j.alcohol.2014.04.005
PMC
PMC4163011
OpenAlex
W2018574373
Cited by
20
References
59
Citations by year
2024: 3 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Alcohol (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (R01-AA016079)
  • Medical Research Service Department of Veteran Affairs (1S10RR023457-01A1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
alcoholism, ondansetron, sertraline, 5-HTTLPR, drug-gene interactions, sex differences, alcohol self-administration, women
MeSH terms
Adult, Alcoholism, Double-Blind Method, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Ondansetron, Sertraline, Serotonin Plasma Membrane Transport Proteins, Receptors, Dopamine D4

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