RCT · 2026
Ketamine boosted deep-sleep brain waves in treatment-resistant depression, not in healthy people
- Original title
- Modulation of early non-rapid eye movement slow wave activity by ketamine in treatment-resistant depression.
- Authors
- Hejazi N, Kheirkhah M, Riedner B, et al.
- Journal
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026
- Molecules
- Ketamine
- Conditions
- Treatment-resistant depression, Healthy volunteers
- Participants
- 133
- Evidence grade
- Moderate
- Source
- Read the original paper
The question
Does a single dose of ketamine change slow brain-wave activity during the first stretch of deep sleep in people with hard-to-treat depression, and does that change track with feeling better?
What they did
Researchers recorded overnight sleep in 91 unmedicated people with treatment-resistant depression (depression that has not responded to standard treatments) and 42 healthy volunteers. Each person was studied at baseline and after both ketamine and placebo, in a randomized, placebo-controlled design across multiple sites. The main measure was slow-wave activity during the first period of non-REM sleep, a marker of deep restorative sleep. They also looked at total sleep time, sleep efficiency, how long it took to fall asleep, and whether age changed the results.
What they found
At the start, people with treatment-resistant depression had lower early-night slow-wave activity than healthy volunteers. Ketamine, but not placebo, raised this slow-wave activity in the depression group, and the increase was most evident in those who responded to treatment. Ketamine had no effect on slow-wave activity in the healthy volunteers. After ketamine, people with depression also slept longer, had better sleep efficiency and fell asleep faster. The increase in slow-wave activity after ketamine was smaller in older participants.
The fine print
The abstract reports directions of effect but almost no effect sizes, so the size of these changes cannot be judged from the record. Sleep brain waves are a biological marker, not a measure of how people feel over time, and the abstract describes only short-term assessments. Participants were unmedicated and enrolled in research studies, so results may not carry over to people taking other medications. This summary is based on the abstract alone.
What it means
In this study, ketamine’s antidepressant response went along with a rebound in deep-sleep brain activity that was already reduced in people with treatment-resistant depression, pointing to sleep as one possible route through which the drug acts.
Evidence grade: Moderate. A placebo-controlled randomized study with a reasonably large sample, but the main outcome is a sleep brain-wave measure rather than a long-term clinical outcome, and follow-up is very short.
This summary is based on the study’s published abstract.