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

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2014-09, Vol.48 (6), p.515-522
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 5-HTTLPR; Adult; Alcohol; Alcoholism - drug therapy; Double-Blind Method; DRD4; Female; Gender; Genotype; Humans; Male; Middle Aged; Ondansetron; Ondansetron - pharmacology; Polymorphism, Genetic; Psychiatry; Receptors, Dopamine D4 - genetics; Serotonin Plasma Membrane Transport Proteins - genetics; Sertraline; Sertraline - pharmacology
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2014.04.005

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