Cognitive effects of ketamine and esketamine treatment for major depressive and bipolar disorder: a systematic review.
Kelei Xiao, Yealin Woo, Christine E Dri et al.
✦ AI-curated · Sources linked
In 30 seconds
This systematic review assessed cognitive outcomes with ketamine and esketamine in adults with major depressive disorder, bipolar disorder, or treatment-resistant depression. It included 22 studies involving 2,441 participants. Randomised trials of single-dose ketamine 0.5 mg/kg or esketamine 0.25 mg/kg in major depressive disorder reported mixed cognitive results, including improvements, no change, and impairment in memory recall or processing speed. Open-label maintenance studies found within-group improvements across several cognitive domains, but lacked comparator-controlled evidence. Whether these changes reflect direct cognitive effects remains uncertain.
Key findings
- The review included 22 studies and 2,441 participants.
- Randomised trials of single-dose ketamine 0.5 mg/kg or esketamine 0.25 mg/kg showed inconsistent cognitive effects.
- Open-label maintenance ketamine 0.5 mg/kg studies reported within-group gains in memory, attention, language, processing speed, and verbal learning.
Why it matters
Cognitive impairment is an important feature of depressive and bipolar disorders, so cognitive outcomes may be relevant alongside mood response when evaluating these treatments. The review suggests possible improvements in several objective domains, but the evidence is not sufficient to distinguish direct procognitive effects from changes related to antidepressant response, practice effects, or comparator differences.
What to keep in mind
Many reported improvements came from uncontrolled or within-group analyses, limiting attribution to treatment. Randomised trial findings were inconsistent.