A single ketamine infusion briefly dialed down the brain network tied to rumination, most in the heaviest ruminators
STUDY: Meiering MS et al, Translational Psychiatry 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial (fMRI mechanistic study)
FUNDING: Boehringer Ingelheim Pharma GmbH & Co. KG
Background
Some patients say they are able to transcend the mental chatter of rumination after a ketamine infusion. Studies show that a single infusion alters the area of the brain involved in rumination for up to 10 days (the default mode network), but until now we’ve lacked controlled data on this effect. This study accomplishes that, but in health subjects, not depression.
This placebo-controlled trial also tested ketamine in combination with lamotrigine, to see if this medication might interfere with ketamine’s benefits by blocking glutamate release.
The Study
- 75 healthy adults (62 analyzed) randomized to oral lamotrigine or placebo pretreatment, then IV ketamine or placebo infusion.
- Resting-state fMRI was scanned before treatment, during infusion, and 24 hours later; a data-driven analysis tracked seven recurring brain network patterns.
- Rumination was measured by self-report.
Results
On brain imaging, ketamine rapidly reduced time in this in rumination-related states (ie, those involving the default mode and frontopareital networks). However, the effect faded by 24 hours. The more intense the rumination, the more pronounced the effect.
Ketamine also reduced time in a somatomotor network during infusion. Lamotrigine reduced both effects a little, but this was not statistically significant.
Unfortunately, the trial only measured rumination at the start, so we don’t know how well these brain changes correlated with clinical changes.
Limitations
Participants were healthy volunteers. The sample was small, ketamine’s psychoactive effects may have partly unblinded participants.
Practice Implications
For many patients with depression, rumination is the chief complaint.
Medications are largely unstudied here, though ketamine and TMS have positive data.
Here are behavioral changes that address rumination. Measure rumination before and after the intervention, whether ketamine or behavioral.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
