Cognitive Effects of Esketamine in Treatment-Resistant Depression: A Systematic Review.
Riccardo Guglielmo, Emma Laura Facchinetti, Daniele Cioci et al.
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In 30 seconds
This systematic review examined cognitive outcomes in adults aged 18 to 80 years with treatment-resistant depression receiving intranasal or intravenous esketamine. Six studies met the inclusion criteria, with cognitive assessments conducted at least 1 month after treatment initiation. Across studies, esketamine was not associated with cognitive deterioration in attention and processing speed, memory, or executive function. Improvements were most consistently reported for attention and processing speed; memory and executive-function benefits were more variable and appeared in some longer-term assessments.
Key findings
- Six studies met the review’s inclusion criteria.
- No cognitive deterioration was reported across the assessed domains.
- Attention and processing speed showed the most frequent and robust improvements, including in RCT-derived datasets and naturalistic longitudinal studies.
- Memory was stable in short-term designs, while memory and executive-function gains were reported in some extended follow-up assessments.
Why it matters
Cognitive impairment can hinder functional recovery in treatment-resistant depression. The review’s findings suggest that esketamine treatment is not accompanied by worsening across the cognitive domains assessed, and may coincide with selective gains, particularly in attention and processing speed. These outcomes may be relevant to understanding functional recovery alongside antidepressant effects, although the evidence remains limited.
What to keep in mind
The evidence is limited to six studies, and the review calls for larger samples, longer follow-up, and harmonized cognitive assessments.