Review: esketamine improved day-to-day and work functioning in depression; no ketamine trials found

The question

Beyond lifting mood, do ketamine and esketamine help people with depression function better at work and in everyday social and family life?

What they did

Researchers searched three research databases up to February 1, 2025 for randomized controlled trials, and re-analyses of those trials, in adults with major depressive disorder or treatment-resistant depression (depression that has not responded to previous treatments). Eligible studies tested intravenous ketamine or nasal spray esketamine against placebo, usual care, antidepressants or other active drugs. The main outcomes of interest were functional impairment, workplace performance and related areas of daily life.

What they found

No controlled studies of intravenous ketamine measuring functional outcomes were found at all, which the authors call a notable gap. Nine studies looked at esketamine. On the Sheehan Disability Scale, a self-report measure of how much symptoms disrupt work, social life and home life, scores dropped by an average of 13.6 points (standard deviation 8.31) with esketamine versus 9.4 points (8.43) with placebo. Work-related measures also improved compared with controls: less overall productivity loss (p = 0.0045), less presenteeism, meaning being at work but working below par (p = 0.0098), and less impairment in regular daily activities (p = 0.0172).

The fine print

The review found no eligible ketamine trials, so nothing can be said about ketamine and functioning. Results were not combined in a formal meta-analysis, and the abstract does not report how many people were included overall, how long the studies lasted, or whether functioning was a main or secondary outcome in each trial. Functioning was measured by self-report, and this summary is based on the abstract alone.

What it means

In randomized trials, nasal esketamine appears to improve not just mood scores but also self-reported ability to work and manage daily life, though the size and durability of that benefit remain unclear and equivalent evidence for intravenous ketamine is missing.

Evidence grade: Moderate. A systematic review limited to randomized trials and their post-hoc analyses, but it pooled no data statistically and included only nine esketamine studies with no total sample size reported.

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