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.
Arketamine, an enantiomer of ketamine, has been less studied than esketamine or racemic ketamine, but recent preclinical work suggests it may have prolonged antidepressant effects and a better safety profile. This scoping review of 20 studies involving 410 subjects found arketamine was primarily investigated for pain management and depression. Early evidence indicates it may reduce pain, though most studies were small and in non-clinical settings. In psychiatry, trials show potential antidepressant effects, but results are inconsistent and some studies unpublished. A consistent finding is arketamine's favorable safety profile, with fewer dissociative and psychotomimetic effects than esketamine or racemic ketamine. Larger, well-designed studies are needed to determine its therapeutic potential.