Review: esketamine did not worsen thinking skills in treatment-resistant depression

The question

Does esketamine, given at low (sub-anesthetic) doses for depression that has not responded to other treatments, harm or help thinking skills such as attention, memory and planning?

What they did

The authors searched the published literature for studies of adults aged 18 to 80 with treatment-resistant depression who received esketamine either as a nasal spray or by intravenous infusion. To be included, a study had to measure cognition at least one month after treatment started. Six studies met the criteria. Results were grouped into three areas: attention and processing speed, memory, and executive function (planning and mental flexibility).

What they found

Across all six studies, esketamine was not associated with worsening in any area of thinking that was measured. Gains in attention and processing speed were the most common and most consistent finding, appearing in both randomized trial data and real-world follow-up studies. Memory stayed stable in shorter studies and improved in those with longer follow-up. Executive function improved mainly in people who already had difficulties at the start and in longer-term assessments; everything else stayed stable.

The fine print

Only six studies were included, and the abstract does not report how many people they covered in total. The studies used different cognitive tests and mixed randomized trials with observational follow-up, so results cannot be combined into a single reliable estimate. Improvements in thinking may simply reflect improvement in depression itself rather than a direct drug effect. This summary is based on the abstract alone.

What it means

The available evidence, though limited, does not suggest that esketamine damages thinking skills in people with hard-to-treat depression, and attention and processing speed may improve. Larger studies using consistent tests and longer follow-up are needed before firmer conclusions can be drawn.

Evidence grade: Low. A systematic review of only six studies that mixed randomized trials with naturalistic follow-up data, with no pooled analysis and no total participant count reported.

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