In adults with treatment-resistant depression, a single intravenous infusion of esketamine (0.25 mg/kg) was non-inferior to ketamine (0.5 mg/kg) for achieving remission 24 hours later. Among 63 participants, 29.4% in the esketamine group and 24.1% in the ketamine group showed remission, a difference of 5.3% that fell within the predefined non-inferiority margin. Depression scores on the Montgomery-Åsberg Depression Rating Scale improved similarly in both groups, and side effects were mild and comparable. The findings suggest that esketamine at half the dose of ketamine offers equivalent short-term efficacy and safety.
Most people with major depressive disorder do not achieve symptom remission, and treatment-resistant depression is defined by the failure of at least one adequate antidepressant trial. This study investigated clinical predictors of depressive symptom remission and response 24 hours and 7 days after infusions of racemic ketamine and esketamine.
Dissociative symptoms are common side effects of ketamine and esketamine used for depression. In adults with treatment-resistant depression randomly assigned to a single 40-minute infusion of either esketamine 0.25 mg/kg or ketamine 0.5 mg/kg, those with higher trait dissociation (measured by the Dissociative Experience Scale) had a greater risk of experiencing induced dissociation (measured by the Clinician-Administered Dissociative States Scale). Every 5-point increase in trait dissociation was associated with a 10.9% increase in induced dissociation. Subjects with high trait dissociation had a 1.41 times higher risk of induced dissociation and a 3.05 times higher risk of very high induced dissociation. Induced dissociation was not a serious adverse effect. The findings suggest screening for trait dissociation and counseling patients on risks.