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.
Drug Discovery Today
February 1, 2023
J. Johnston, Maximillian Greenwald, I. Henter et al.
64 citations
Stress triggers inflammation in the brain, a pattern also seen in the blood of people with depression. This stress-induced inflammation may contribute to treatment-resistant depression. The rapid-acting antidepressant ketamine works partly by reducing inflammation through effects on the HPA axis, the kynurenine pathway, or by suppressing cytokines. Understanding the link between ketamine, inflammation, and stress could reveal how ketamine works and lead to new rapid-acting antidepressants that target inflammation.