Esketamine nasal spray is an NMDA receptor antagonist which is FDA approved, in conjunction with an oral antidepressant, for treatment- resistant depression (TRD) in adults. Dissociation is a well-known side effect to treatment and can be measured using the CADSS (Clinician Administered Dissociative States Scale). To date, patient specific factors that may contribute to the severity of dissociation have not been described.

This case series describes two patients receiving treatment with 84-mg esketamine nasal spray twice weekly in an outpatient clinic for TRD who experienced an episode of significant dissociation several months into their treatments. History obtained prior to esketamine treatment included an assessment for any recent stressors. CADSS score was assessed posttreatment.

Case 1 was a 55-year-old female who had been receiving esketamine for over two months who presented to the clinic complaining of recent sleep-deprivation while caring for her newborn grandchild. Patient experienced extreme dissociation following administration of esketamine, verbalizing that she felt “very big” and began twitching, grimacing, moaning, and repeating nonsensical statements. CADSS score after treatment was 27. Case 2 involves a 59-year-old female with a remote history of sexual trauma who was four months into esketamine treatments when she presented to the clinic feeling sad after listening to another sexual assault victim’s testimony on social media prior to treatment. Shortly after receiving esketamine, she began experiencing a flashback to previous trauma and screaming loudly. CADSS score after treatment was 21. Although both patients reported a history of dissociation with esketamine treatments in the past, they both reported that the level of dissociation they experienced during the above sessions was far more severe.

Severe episodes of dissociation during treatment with esketamine in patients with TRD may be associated with patient specific factors. Assessing patients for the presence of recent stressors or changes to their routine prior to each treatment session may help healthcare professionals predict the risk of severe dissociation and allow providers to better prepare to support patients during these experiences.

No Funding