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.
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.
Subcutaneous (SC) ketamine shows promise as a rapid and effective antidepressant for unipolar and bipolar depression, with response and remission rates ranging from 50 to 100% after single or multiple doses. Doses of 0.1 to 0.5 mg/kg of racemic ketamine and 0.5 to 1 mg/kg of esketamine were used, administered weekly or twice-weekly, often with dose titration. Side effects were temporary. This systematic review of 12 studies (two randomized trials, five case reports, and five retrospective studies) found SC ketamine to be a convenient and cost-effective route, particularly relevant for developing countries, though a meta-analysis was not possible due to heterogeneity. Further research comparing SC with intravenous and intranasal protocols is needed.
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.