Nasal ketamine vs esketamine for hard-to-treat depression: similar scores, fewer remissions

The question

For adults with depression that has not responded to other treatments, does off-label intranasal racemic ketamine work about as well as the approved intranasal esketamine?

What they did

Researchers reviewed records from a single centre for 76 adults with treatment-resistant depression. Thirty-one had received intranasal esketamine and 45 had received off-label intranasal racemic ketamine, both over an eight-session, four-week starting phase. They analysed the data using a “target trial” approach, which tries to mimic a randomized trial using existing records. The main outcome was change on the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated depression score; remission was defined as a MADRS score of 12 or less.

What they found

Both groups improved by a similar amount on the depression scale: an average drop of 9.3 points with esketamine and 10.0 points with ketamine (p = 0.41), which met the study’s pre-set bar for ketamine being no worse (a difference of less than 3 points). Remission was more common with esketamine (38.7%) than with racemic ketamine (15.6%; odds ratio 0.29, 95% confidence interval 0.10 to 0.86), so ketamine did not meet the bar for remission. A Bayesian analysis put the probability that esketamine was better on remission at 98.6%. Side effect profiles were similar, though ketamine was linked to slightly more short-lived rises in blood pressure.

The fine print

This was a retrospective chart review, not a randomized trial, so patients were not assigned by chance and hidden differences between the two groups could explain the remission gap. The sample was small (31 versus 45 people) and came from one centre, and follow-up covered only the four-week starting phase. The abstract does not report doses or longer-term outcomes. This summary is based on the abstract alone.

What it means

In this real-world record review, both nasal ketamine and esketamine were followed by similar average drops in depression scores, but full remission was more common with esketamine. Randomized studies would be needed to know whether that difference is real.

Evidence grade: Low. Retrospective observational study at a single centre with 76 patients, no randomization and no placebo group, so treatment choice and unmeasured differences between groups could affect the results.

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