Another intriguing series of experiments have focused on tailoring medications for alcoholism that act via serotonergic modulation. Two drugs, ondansetron and sertraline, are worth mention for their differential efficacy in the context of individual genotype (short S versus long L) at the promoter polymorphic region (5-HTTLPR) of the serotonin transporter (SLC6A4; 5-HTT) gene. Ondansetron is an antagonist of the serotonin (5-HT3) receptors. One study found that the most substantial reduction in drinks/day and days abstinent upon treatment was noted in those who were homozygous for the long (LL) allele of 5HTTLPR and the T allele of a 3′ untranslated region (UTR) variant, rs1042173, putatively due to increased drug-provoked blockade of upregulated post-synaptic serotonin receptors in LL/TT individuals [116, 117]. Sertraline, on the other hand, is a selective serotonin reuptake inhibitor (SSRI) and has been found to be more efficacious, in general, in those with comorbid depression [118]. These observations led to the finding that while sertraline was beneficial in LL individuals who were late-onset alcoholics (typically comorbid with internalizing features [118], it performed worse than placebo in early-onset cases [119], particularly in the context of daily anxiety.
