The Aligned Study is an investigator-initiated, randomized controlled trial of pharmacogenomic-guided therapy versus standard care for people with depression who require initiation or change in antidepressant therapy. This multisite study aims to recruit 776 participants across Australia, with the primary outcome being remission in depression by 12 weeks on antidepressants (as measured by MADRS score). By comparing antidepressant treatment based on pharmacogenomic guided versus standard treatment, we aim to measure if pharmacogenomic testing provides a benefit for people with moderate to severe depression, leading to quicker and greater improvement of depression symptoms and a reduction in side effects experienced.