Differed spontaneous dissociative symptoms following the use of esketamine intranasal spray in a patient suffering from treatment-resistant depression: a case report

Intranasal esketamine is used in France for treatment-resistant depression. Dissociative symptoms are common side effects during treatment sessions. We report a case of delayed spontaneous dissociative symptoms following esketamine administration. A 20-year-old female with treatment-resistant depression received esketamine treatment. Dissociative symptoms occurred during sessions and persisted at a distance, often accompanied by anxiety. Delayed dissociative phenomena disappeared within the fourth week of treatment by esketamine. The literature mainly discusses dissociation during esketamine treatment sessions, with limited data on differed spontaneous episodes. Three hypotheses are discussed concerning the mechanism of occurrence of these dissociative phenomena, including esketamine’s direct effect, central nervous system sensitization, and anxiety-induced dissociation. We present the first case of differed spontaneous dissociative effects after intranasal esketamine administration for treatment-resistant depression. Our main hypothesis suggests that esketamine may act as a ‘pattern’ for dissociative experiences, heightening the patient’s ability to discern these phenomena during other instances of dissociation, such as acute anxiety attacks. Further research is needed to validate this hypothesis.