The evidence map above is from a recent review by the Yale ketamine group, suggesting no evidence of neurotoxicity or cognitive problems in antidepressant doses
Repeated infusions don’t dull the mind, and patients who improve say they think more clearly
STUDY: Nomoto K et al, Pharmacopsychiatry 2026
STUDY TYPE: Randomized controlled trial
FUNDING: SENSHIN Medical Research Foundation, Japan Society for the Promotion of Science, Keio Next-Generation Research Project Program, Japan Research Foundation for Clinical Pharmacology, Takeda Science Foundation
Background
Ketamine impairs cognition in high doses and recreational use, but what about repeated infusions of the lower doses used for depression? This controlled study, though small, adds to the limited knowledge we have there.
The Study
- Thirty-four Japanese outpatients with treatment-resistant depression on either ketamine (0.5 mg/kg) or saline, twice weekly for two weeks.
- Assessors blind to treatment ran a full cognitive battery, testing memory, attention, working memory, and inhibitory control, before and after the infusions.
Results
Ketamine didn’t change objective measures of cognition. No better, no worse.
On subjective measures, ketamine responders reported much sharper thinking than non-responders, a 79% improvement versus 20%. The more their mood improved, the more their sense of cognitive benefit, suggesting this may be a matter of perspective than an objective difference.
The authors also found a signal worth further study. Patients with weaker inhibitory control at baseline, meaning they had more trouble shutting off intrusive thoughts, responded better to ketamine (p = 0.004). That makes sense, as ketamine turns down ruminative thinking in controlled trials, an effect that lasts for about a week after the infusion.
Limitations
Small, likely had functional unblinding.
Practice Implications
- Despite initial concerns, ketamine does not seem to harm cognition, and this study adds to that growing body of evidence.
- Consider ketamine for treatment resistant depression with high rumination. Learn how to pair ketamine with psychotherapy in Difficult to Treat Depression.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
