Physiological markers of rapid antidepressant effects of allopregnanolone

The rise of ketamine and brexanolone as rapid antidepressant treatments raises the question of common mechanisms. Both drugs act without the long onset time of traditional antidepressants such as selective serotonin reuptake inhibitors. The drugs also share the interesting feature of benefit that persists beyond the initial drug lifetime. Here, we briefly review literature on functional changes that may mark the triggering mechanism of rapid antidepressant actions. Because ketamine has a longer history of study as a rapid antidepressant, we use this literature as a template to guide hypotheses about common action. Brexanolone has the complication of being a formulation of a naturally occurring neurosteroid; thus, endogenous levels need to be considered when studying the impact of exogenous administration. We conclude that network disinhibition and increased high-frequency oscillations are candidates to mediate acute triggering effects of rapid antidepressants.