Serotonin transporter genotype interacts with paroxetine plasma levels to influence depression treatment response in geriatric patients

Objective To investigate whether variable antidepressant response may be influenced by an interaction between the serotonin transporter promoter polymorphism (5-HTTLPR) and antidepressant concentration. Methods Elderly subjects with depression treated with paroxetine (n = 110) were genotyped and assessed with the Hamilton Rating Scale for Depression (HAMD). A mixed-effect analysis of repeated measures was used. Results There was an interaction between early paroxetine concentration and 5-HTTLPR genotype on symptomatic improvement over 12 weeks (F18,59.5 = 1.8, p < 0.05), as well as main effects of both paroxetine concentration (F68,55.3 = 2.4, p < 0.005) and genotype (F2,74.2 = 5.7, p < 0.005). Paroxetine concentrations were correlated with change in HAMD scores after 2 weeks of treatment in subjects with the short (s) allele (r = 0.31, p < 0.05) but not in subjects homozygous for the long (l) allele. Conclusion The results demonstrate a concentration–response relation for paroxetine in late-life depression and support the hypothesis for both a direct main effect and a moderating influence of 5-HTTLPR alleles on this concentration–response relation.