A single intravenous infusion of arketamine (0.5 mg/kg) rapidly reduced depression severity in seven people with treatment-resistant depression. The Montgomery–Åsberg Depression Rating Scale score fell from an average of 30.7 before infusion to 10.4 after one day, a mean drop of 20.3 points. Dissociative side effects were nearly absent. The findings suggest arketamine may produce fast-onset and sustained antidepressant effects with a favorable safety profile, as previously observed in animals, but controlled trials are needed to confirm.
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.