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.
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.
Among people with treatment-resistant depression, the intensity of dissociation caused by a single infusion of ketamine or esketamine is linked to greater antidepressant effect one day later, but only when dissociative symptoms are mild to moderate. For every one-point increase on a dissociation scale up to 15 points, depression scores improved by an average of 0.5 points after 24 hours. This relationship was not observed at 72 hours or 7 days after infusion. The study was not originally designed to test this relationship, so confounding factors were not controlled, and the finding should be considered suggestive rather than definitive.