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Not So Fast: Recent Successes and Failures in Treating Depression.

Historically, rapid antidepressant effects within days to weeks were seen in response to electroconvulsive therapy (ECT). In contrast, antidepressant medications took 4 to 6 weeks to exert their antidepressant effects. However, trials with novel, rapid-acting antidepressant medications—including the glutamatergic modulator ketamine—have revolutionized our expectation of when antidepressant effects could be expected, that is, in a matter of hours or days instead of weeks or months. This paradigm shift has instilled hope in individuals struggling with depression, particularly treatment-resistant depression (TRD). The unmatched robustness of ketamine’s effects, the notable recent FDA approval of its derivative esketamine for adults with TRD, and the recent approval of brexanolone for postpartum depression (PPD) underscore the first exemplars of a mechanistically novel and distinct antidepressant agent in decades. Yet, despite tremendous progress, challenges have arisen in our investigation of many promising, novel, and rapid-acting (as well as non–rapid-acting) antidepressant interventions for depression. Here, we briefly assess some of these recent successes and setbacks.