First Reported Case of Dissociative Symptoms Associated With Zuranolone Use in Peripartum Depression

Peripartum depression is commonly observed in women during or after pregnancy. While selective serotonin reuptake inhibitors remain a mainstay of treatment, novel neurosteroid-based therapies such as brexanolone and zuranolone offer promising, rapid-acting alternatives.  We have reported the first known case of dissociative symptoms temporally associated with zuranolone use. A woman in her early 50s with a history of post-traumatic stress disorder (PTSD) and bipolar 1 disorder presented to the emergency department on the seventh day of zuranolone therapy, exhibiting profound disorientation, impaired autobiographical recall, unsteady gait, and communication difficulties. She had restarted zuranolone after discontinuing it earlier due to initial side effects, including dizziness and mood worsening. Her laboratory and imaging workup were unremarkable, and her symptoms resolved within 10 hours of discontinuation of zuranolone with supportive care alone. This case raises important concerns about the safety of neurosteroids in individuals with a history of trauma, particularly due to the potential overlap between GABAergic modulation and dissociative symptoms. Dysregulation of GABA_A receptors has been implicated in both PTSD and memory processes, suggesting a plausible neurobiological mechanism underlying dissociative effects of zuranolone. Further research is necessary to clarify the associations and determine the safety profile of neurosteroids in patients prone to dissociation. Given the growing use of zuranolone in primary care and obstetrical and gynecological settings where psychiatric consultation may be limited or absent, clinicians should be vigilant for dissociative symptoms, especially in trauma-exposed populations. This report underscores the need for thorough psychiatric evaluation before initiating neurosteroid treatment and highlights gaps in access to psychiatric care that may hinder optimal management of complex peripartum presentations.