Journal of Affective Disorders
February 18, 2014
D. Luckenbaugh, M. Niciu, D. Ionescu et al.
282 citations
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.
Molecular Psychiatry
February 27, 2018
A. Nugent, Elizabeth D. Ballard, T. Gould et al.
254 citations
In a double-blind, placebo-controlled, randomized cross-over trial with 35 unmedicated people with major depressive disorder (MDD) and 25 healthy controls, ketamine (0.5 mg/kg) improved depressive symptoms in MDD subjects but caused modest, temporary increases in depressive symptoms in healthy controls. Both groups showed increased resting gamma power measured by magnetoencephalography. Among MDD subjects, gamma power did not directly predict the size of the antidepressant effect. However, baseline gamma power moderated the link between post-ketamine gamma and response: higher post-ketamine gamma was tied to better response in those with low baseline gamma, but the opposite pattern appeared in those with high baseline gamma. This suggests biological subtypes based on homeostatic dysregulation and cautions against inferring ketamine's mechanism solely from studies of healthy controls.
Journal of Affective Disorders
February 17, 2018
M. Niciu, Bridget J. Shovestul, Brittany A. Jaso et al.
134 citations
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.