Association between serotonin transporter gene promoter-region polymorphism and 4- and 12-week treatment response to sertraline in posttraumatic stress disorder

Abstract

We examined the association between serotonin transporter (5HTTLPR) genotype (SS vs SL vs LL) and sertraline treatment outcome in posttraumatic stress disorder (PTSD). Outpatients (n=330) with PTSD underwent 5HTTLPR genotyping. All patients received sertraline (100 mg/day) for 12 weeks. Patients were assessed using the Clinician-Administered PTSD Scale (CAPS) and other instruments. Patients and rater were blind to the genotyping results. The primary outcome was completer sample CAPS improvement at 12 weeks. Response was defined as ≥30% improvement in CAPS total score with a CGI-I score of 1 or 2. The discontinuation rate was 31.5%. Adverse events led to drop out in 18.1%, 15.3%, and 5.9% of SS, SL, and LL patients, respectively (P=0.038). Among completers, there were 95, 43, and 88 patients with the SS, SL, and LL genotypes, respectively. At endpoint, CAPS total scores improved by 26% vs 46%, respectively, in SS and SL vs LL patients (P<0.001); much of this improvement (15% vs 31% in SS and SL vs LL patients, respectively; P<0.001) was apparent by week 4. The findings were largely similar for the other outcome measures. The response rate was 0%, 0%, and 47.7% in the SS, SL, and LL groups, respectively (P<0.001). We administered a fixed dose of sertraline. For sociopolitical reasons, we planned a completer analysis only. Relative to the SS and SL 5HTTLPR genotypes, the LL genotype is associated with greater responsiveness of PTSD to sertraline (100mg/day) and with lower drop out due to adverse events. The S allele is associated with a striking specificity for treatment nonresponse, as defined in this study.