A protocol describes a planned randomized, controlled, double-blind noninferiority trial comparing a single infusion of esketamine (0.25 mg/kg) with racemic ketamine (0.5 mg/kg) for treatment-resistant depression. The primary outcome is remission rates at 24 and 72 hours after infusion. Secondary outcomes include cognition, dissociation, and blood biomarkers. The authors state that no study has directly compared these two forms, and a head-to-head test is needed to see if esketamine is comparable in efficacy and safety.
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.