Precision medicine for depression: development of a decision-support tool based on the PRIME randomized controlled trial

Abstract Many patients with major depressive disorder (MDD) do not respond to their first antidepressant, and clinicians lack an empirical basis for deciding whether to continue or change treatment after an initial trial. We analysed the Precision Medicine in Mental Health Care (PRIME) pragmatic randomized controlled trial, in which 1,944 US veterans were randomized to usual care enhanced by pharmacogenetic testing or to usual care alone. Using decision tree analysis in the 1,307 participants who had not responded after four weeks, four characteristics separated those with the highest (39.9±10.5%) and the lowest (11.1±3.0%) likelihood of week-12 treatment response: symptom improvement at week 4, better physical health, availability of pharmacogenetic test results, and absence of post-traumatic stress disorder. The resulting decision-support tool identified 77% of week-4 partial and non-responders as candidates for a treatment change. This preliminary tool requires validation in independent samples before prospective clinical evaluation.