In treatment-resistant inpatients with major depressive or bipolar disorder, the dissociative side effects of a single ketamine infusion predicted a more robust and sustained antidepressant response. Greater dissociation measured 40 minutes after infusion correlated with greater improvement in depression scores at 230 minutes and 7 days later. In contrast, psychotomimetic symptoms, manic symptoms, and changes in blood pressure or pulse were not significantly linked to antidepressant efficacy. The findings suggest that dissociation, rather than other side effects, may be a marker or mediator of ketamine's antidepressant action, though further prospective research is needed.
Depersonalization—a feeling of detachment from one's own body or thoughts—was the dissociative symptom most strongly linked to ketamine's antidepressant effect in patients with treatment-resistant depression. Analyzing data from 126 patients with major depressive or bipolar disorder who received a single ketamine infusion, researchers found that higher scores on the depersonalization subscale of the Clinician-Administered Dissociative States Scale consistently predicted greater improvement in depression ratings across multiple time points. Derealization (feeling the world is unreal) showed a weaker and less consistent association, while amnesia was unrelated to antidepressant response. The finding suggests that depersonalization and antidepressant response may share neurobiological mechanisms, though off-target effects cannot be ruled out.