What if STAR*D Had Been Placebo-Controlled? A Critical Reexamination of a Foundational Study in Depression Treatment

These findings raise questions about the evidence supporting widely used treatment strategies following an inadequate response to an initial antidepressant. They suggest that pragmatic trials should be interpreted cautiously in the absence of blinded placebo-controlled studies and point to the need for high-quality blinded clinical trials of second-step and third-step depression treatments.