Significance Statement
TRD, investigator-reported, treatment-resistant depression, delusions, Hallucinations, psychotic symptoms
ADVERSE EVENTS, EVENTS, ADVERSE EVENT
Transient dissociation has been reported with esketamine treatment. Results of a post hoc analysis presented here further characterize the nature and severity of dissociation reported in an open-label phase 3 study (SUSTAIN-2) of esketamine plus a newly initiated oral antidepressant in participants with treatment-resistant depression (TRD). After the first esketamine dose, dissociation was reported as an adverse event in 14.3% (109/764) of patients. Investigators characterized most dissociation events as mild (n = 78), some as moderate (n = 26), and few (n = 5) as severe. Severity of most items of the Clinician Administered Dissociative States Scale (CADSS) increased with the severity of investigator-reported dissociation events. No CADSS cutoff point discriminated well between the presence and absence of investigator-reported dissociation adverse events. Hallucinations or delusions were reported as adverse events in 5 and 0 patients, respectively. In summary, no signature profile of dissociative experiences was revealed, and psychotic symptoms were uncommon.