In this episode of PsyQ, we perform a forensic analysis of the landmark OPTIMUM trial, a study that fundamentally reshapes the treatment algorithm for resistant depression in older adults. We dissect the head-to-head battle between switching antidepressants versus augmentation, revealing why aripiprazole claims the crown for efficacy while exposing a counterintuitive and critical safety signal regarding bupropion-induced falls. Beyond the clinical pearls, we guide you through the statistical machinery under the hood—specifically how the Benjamini-Hochberg procedure saved the study's primary finding—and introduce the "Rule of Three," a data-driven threshold that suggests exactly when clinicians should stop cycling medications and pivot to interventional psychiatry.

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