Ketamine's rapid antidepressant effects are linked to enhanced neuroplasticity in the amygdala and hippocampus, brain regions involved in fear and learning. Anxiety during ketamine infusion is associated with poorer treatment outcomes. In a single-blind, placebo-controlled study, 17 healthy volunteers received placebo then 0.5 mg/kg ketamine intravenously. Anxiety was measured using the 5D-ASC score, and brain scans were taken 4 hours after infusion. Smaller hippocampal head volume significantly predicted greater anxiety (β = -0.733, p = 0.006), with similar trends for subfields. Hippocampal subfield volumes may help predict anxiety-related experiences during ketamine use and potentially treatment outcomes.
Modern electroconvulsive therapy (ECT) and ketamine are the most effective treatments for depressed patients who do not respond to two or more antidepressants. Recent large head-to-head comparisons of intravenous ketamine versus ECT for treatment-resistant depression have produced conflicting findings, largely because of major differences in patients' baseline characteristics and treatment procedures across studies. This commentary argues that treatment decisions between ECT and ketamine should rely on predictive clinical response markers and patient preferences, not on direct comparisons that are methodologically limited. It also emphasizes that since ketamine is usually given before ECT, future studies should examine ECT's effectiveness specifically in patients who did not respond to ketamine.