Postpartum Depression: Zuranolone, Emerging Therapies, and Screening for Birth Trauma

Katie Unverferth, MD, discussed advances in postpartum depression (PPD) treatment, the clinical phenomenology of PPD, and emerging pharmacological and investigational approaches, at the 2026 Southern California Psychiatry Conference.

Unverferth pointed to PPD as an often anxious depression marked by ruminative and circular thinking. She noted that intrusive thoughts are nearly universal in the postpartum period—with studies indicating that thoughts of accidental harm to the infant occur in approximately 95% of postpartum women and thoughts of intentional harm in approximately 54%—and emphasized that these thoughts do not reflect intent and are associated with a decreased rather than increased likelihood of infant harm.¹ She argued that proactively screening for and normalizing intrusive thoughts can be transformative for patients who might otherwise interpret them as evidence of psychosis or dangerous intent.

On the pathophysiology of PPD, Unverferth described a GABAergic-glutamatergic dysregulation model driven by hormonal fluctuations during pregnancy and the early postpartum period, and highlighted neuroactive steroids—specifically zuranolone, the first approved oral treatment for PPD—as agents that target this mechanism directly.² She noted that zuranolone is administered once nightly for 14 days and that its approval represents a significant advance in the field. She also discussed emerging treatments including transcranial magnetic stimulation, for which she characterized the evidence base as relatively well developed, and esketamine, which she noted that data remain early but that studies of postpartum esketamine infusions for prophylaxis of PPD in women with mild prenatal depressive symptoms showed promise. She briefly mentioned RE104 (luvesilocin), an investigational psychedelic compound from Reunion Neurosciences that recently reported positive phase 2 clinical data as a single-infusion treatment for PPD, with phase 3 data pending.

On screening, Unverferth emphasized birth trauma as an underappreciated but clinically significant risk factor for PPD, noting that the subjective experience of birth—including feelings of loss of control or dissociation—often matters more than objective obstetric events. She recommended the Edinburgh Postnatal Depression Scale as a validated screening tool, and identified inability to sleep when the infant sleeps—particularly when driven by anxiety or ruminative thinking—as a clinically meaningful red flag. She also cited biomarker research aimed at identifying predictors of PPD in the third trimester as an exciting emerging direction.

Dr Unverferth is director of the UCLA Women's Life Center and medical director of the Maternal Mental Health Program at UCLA. She also maintains a private practice in Santa Monica, California.

References

1. Collardeau F, Lu OL, Albert AYK, et al. Prevalence and course of unwanted, intrusive thoughts of infant-related harm. J Clin Psychiatry. 2024;85(3):23m15145.

2. Deligiannidis KM, Meltzer-Brody S, Maximos B, et al. Zuranolone for the treatment of postpartum depression. Am J Psychiatry. 2023;180(9):668–675.