Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed class of antidepressants. However, SSRIs are frequently ineffective and precision medicine approaches are strongly needed to optimize treatment efficacy. DNA methylation levels of serotonin transporter (SLC6A4m) and tryptophan hydroxylase 2 (TPH2m) genes have been suggested as predictive biomarkers of antidepressant efficacy. In this study, we aimed to evaluate SLC6A4m/TPH2m biomarker potential and compare with previous findings in an independent cohort of N=77 patients with major depressive disorder who were treated with escitalopram for 12 weeks. Methylation of 4 and 6 CpG sites in the promoter region of SLC6A4 and TPH2 respectively was quantified by bisulfite pyrosequencing. Depressive symptoms were measured at baseline, after 8 and 12 weeks of treatment using the Hamilton Depression Rating Scale (HAMD). Latent variable models, logistic regressions and multiple linear regressions were used to evaluate the association between pre-treatment SLC6A4m/TPH2m and a) treatment response; b) HAMD change after 8/12 weeks of treatment. Cell proportions, age, sex, baseline HAMD score and genotype information were included as covariates. We found an association between baseline TPH2m and both treatment response (Estimate=3.58; p=0.02; 95% CI[0.50; 6.67]) and change in depressive symptoms after 8 weeks of treatment (Estimate=-58.75; p=0.03; 95%CI[-111.51; -6.00]). In addition, similar to previous observations, we found a trend between SLC6A4 CpG2 (chr17:30,236,083) and HAMD change after 12 weeks (Estimate=9.29; p=0.05; 95% CI[-0.01;18.59]).Our findings suggest that TPH2m and SLC6A4m may be informative of antidepressant treatment outcome. However, future studies are needed to validate the clinical relevance of TPH2m/SLC6A4m.