Systematic review · 2026
Review of how ketamine and related drugs affect sleep in depression
- Original title
- The effect of glutamatergic modulators on sleep behavior and architecture in depressive disorders: A systematic review.
- Authors
- Valentino K, Ballum H, Cheung W, et al.
- Journal
- Journal of psychiatric research, 2026
- Molecules
- Ketamine, Esketamine, Other
- Conditions
- Depression, Other
- Evidence grade
- Low
- Source
- Read the original paper
The question
Do drugs that act on the brain’s glutamate system, such as ketamine, change sleep in people with depression, and could better sleep be part of how they work?
What they did
The authors searched seven research databases from their earliest records up to November 27, 2024, following standard systematic review guidelines. Three reviewers screened and selected studies. They included both laboratory (animal) and human studies that reported effects of glutamate-acting drugs on sleep behaviour, sleep architecture (the pattern and stages of sleep), or the biological mechanisms behind sleep. Results were described in narrative form rather than pooled statistically.
What they found
The review notes that about 80% of people diagnosed with major depressive disorder report insomnia symptoms. Laboratory studies suggested ketamine acts on brain systems involved in sleep, including serotonin, dopamine and GABA pathways, affects slow-wave (delta) brain activity during non-dreaming sleep, and normalizes the activity of certain body-clock genes. Esketamine increased delta activity during non-dreaming sleep, while arketamine did not. Drugs acting on mGlu2/3 receptors were reported to reduce dreaming (REM) sleep. In human studies, improvement in sleep among people with depression appeared to help explain part of ketamine’s antidepressant effect.
The fine print
The review mixes animal and human research, and the abstract does not say how many studies or people were included, nor how the human studies were designed. Findings are described narratively rather than combined statistically, so the size of any sleep benefit is unclear. Mediation findings (sleep improvement explaining antidepressant effects) come from associations, not proof of cause. This summary is based on the abstract only.
What it means
Sleep changes may be part of how ketamine and similar drugs affect depression, but the current evidence is descriptive and mixes animal with human findings, so firm conclusions are premature.
Evidence grade: Low. A systematic review that combines animal and human studies and describes findings narratively, without pooled numbers or a stated total number of participants.
This summary is based on the study’s published abstract.