Review: IV ketamine for treatment-resistant depression showed no cognitive decline

The question

Does low-dose intravenous ketamine harm or help thinking skills in people with depression that has not responded to standard treatments?

What they did

Researchers searched four large research databases up to May 15, 2025 for studies on ketamine, depression and cognition, and registered their plan in advance. They included 21 studies covering roughly 900 to 1,180 people with treatment-resistant depression, meaning depression that had not improved with previous treatments. They looked at tests of processing speed, working memory, attention, verbal and visual memory, mental flexibility and executive control, and rated each study for risk of bias. Results were described rather than combined into a single pooled number.

What they found

Improvements in thinking were most often reported for processing speed and working memory. Attention scores were either unchanged or modestly better, while verbal and visual memory results varied widely between studies. Executive control, especially performance on the Stroop test of mental inhibition, improved in several trials. No study reported worsening of cognition. Only two of the 21 studies directly examined the link between cognition and suicidal behaviour, so the suggested connection remains a hypothesis.

The fine print

The review counted studies rather than pooling their data, so no overall effect size is given, and the participant total is reported only as an approximate range. The included studies used different cognitive tests and included non-randomized designs, which makes results hard to compare. Repeated testing can improve scores simply through practice, and follow-up periods were not described as long-term. This summary is based on the abstract only.

What it means

Across the available studies, low-dose intravenous ketamine did not appear to dull thinking in people with hard-to-treat depression, and some mental skills such as processing speed and working memory tended to improve. Longer, standardized studies are still needed to know whether those gains last or matter clinically.

Evidence grade: Low. A narrative systematic review that pools no results and includes both randomized and non-randomized studies with varied cognitive tests.

This summary is based on the study’s published abstract.