EEG changes after ketamine in older veterans with treatment-resistant depression

The question

Does a single ketamine infusion change the way multiple brain regions co-ordinate their activity, and do those changes track who gets better from depression?

What they did

Researchers re-analyzed data from a randomized, double-blind trial (neither patients nor raters knew who got what) in 30 older military veterans with treatment-resistant depression, meaning depression that had not responded to standard treatments. Eighteen received a single 40-minute intravenous infusion of ketamine (at 0.1, 0.25 or 0.5 mg/kg) and 12 received midazolam, a sedative used as a comparison drug, at 0.03 mg/kg. EEG (a recording of electrical brain activity from the scalp) was collected at rest and during a listening task at baseline, 1 hour, 24 hours and 7 days after the infusion. They applied a measure called O-information, which looks at how three or more brain signals share information, rather than just pairs.

What they found

Ketamine shifted these multi-region brain interactions over time. The largest change was in alpha-band activity at 1 hour after the infusion (Cohen’s d = 2.57, a very large statistical effect size in this small sample), which faded by 24 hours and moved toward the theta band, then partly reappeared in beta and gamma bands by Day 7. Statistical modelling found group differences across most frequency bands, strongest for alpha, beta and gamma redundancy. Larger increases in alpha-band redundancy at 24 hours were associated with greater improvement in depression symptoms at Day 7 (β = 69.31, q = 0.05), and some brain measures also tracked dissociation, the temporary sense of detachment ketamine can cause.

The fine print

Only 30 people took part, split unevenly between drugs, and the ketamine group received three different doses, so dose effects cannot be separated. This was a secondary, exploratory analysis not designed to test these brain measures, and the authors describe the links to symptom change as exploratory. Follow-up ended at 7 days, participants were older veterans (so results may not apply to other groups), and this summary is based on the abstract alone.

What it means

Ketamine appears to reorganize how brain regions share information, and some of those changes lined up with symptom improvement a week later, but this is early, small-sample work rather than a usable clinical test.

Evidence grade: Low. A small secondary (after-the-fact) brain-recording analysis of a randomized trial with only 30 people, mixed ketamine doses and exploratory statistics.

This summary is based on the study’s published abstract.