Temporal Dynamics of Antidepressant Response Following Brexanolone Treatment in Postpartum Depression

Rachel Kozik, BA; Riah Patterson, MD; Elizabeth Andersen, PhD; Frank W. Putnam, MD; David Rubinow, MD

J Clin Psychiatry 2026;87(2):25m16144

Abstract

Objective: Major depressive disorder with peripartum onset (also known as postpartum depression [PPD]) (DSM-5) is a debilitating condition that can be characterized by difficulty transitioning out of a negative affective state. Given the rapid clinical response typically observed with brexanolone, the treatment period provides a rare opportunity to study the dynamics of this transition. The present study examined the timing and pattern of symptom changes, including leading and residual symptoms and associated changes in self-reported maternal functioning.

Methods: Using a single-arm, open-label, descriptive pilot study, 10 women with moderate-to-severe PPD received a 60-hour intravenous infusion of brexanolone following the FDA-approved regimen. Symptoms comprising the affective state were assessed at high frequency before, during, and after the infusion to track the timing and sequence of symptom changes. Exploratory analyses used repeated-measures analysis of variance with Greenhouse-Geisser correction and post hoc comparisons with adjustment for multiple measures. Data were collected from July 2022 to November 2023.

Results: All participants showed clinical response, and most reached remission within 44 hours. Symptom improvement was broad, though no single symptom consistently led the affective shift. The timing of maximal change in subjective satisfaction with mood often differed from changes in standard symptom scales. Significant (P<.001) improvements were observed in anhedonia (↓89%), rumination (↓29%), and (↑56%) maternal functioning, all of which persisted at 30-day follow-up.

Conclusions: This study provides novel insights into the rapid and individualized symptom trajectories during recovery from PPD following brexanolone infusion. These findings could have broader implications for understanding the pathophysiology of mood disorders and for developing targeted interventions that modulate brain dynamics to promote recovery from pathological affective states.

Trial Registration: ClinicalTrials.gov identifier: NCT05543746.

J Clin Psychiatry 2026;87(2):25m16144

Author affiliations are listed at the end of this article.

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