Given that both β-arrestin 1 levels and ARRB1 genetic variants have been associated with MDD and ATD treatment response, the objectives of this study were to analyze the association of clinical response following ATD treatment in a cohort of 6-month ATD-treated MDD patients, with 1) the set of rare variants and 2) frequent variants with likely functional consequences, identified from exonic, intronic, and 5′- and 3′-untranslated regions of ARRB1. This evidence concerns the gene ARRB1 and major depressive disorder.