Our study adds new knowledge of the associations between CYP2C19 and CYP2D6 phenotypes and antidepressant switching, discontinuation, emergency department contacts, and suicide attempt/self-harm in children, adolescents, and adults with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine, which indicates the clinical utility of PGx in patients with depression. Here, CYP2D6 is linked to major depressive disorder.