Randomized trial of ketamine masked by surgical anesthesia in patients with depression.
Level 2 - randomized trial
Single-center randomized triple-blind placebo-controlled trial
PubMed 38188539 · doi:10.1038/s44220-023-00140-x
What was done
In a single-center, parallel-arm, triple-masked, randomized controlled trial (NCT03861988), 40 adult patients with major depressive disorder scheduled for routine surgery received a single intravenous infusion of either ketamine (0.5 mg/kg) or saline placebo during standard surgical anesthesia. Participants, investigators, and clinical care staff were masked to allocation. Depression severity was evaluated via the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1, 2, and 3 days post-infusion. Masking success was assessed by asking participants to guess their assignment after all follow-up visits.
What was found
A mixed-effects model showed no statistically significant effect of treatment assignment on MADRS depression scores across days 1–3 (-5.82, 95% CI -13.3 to 1.64, p = 0.13). Masking was successful: 36.8% of participants guessed their assignment correctly, with guesses distributed in similar proportions in both groups.
Why it matters
When psychoactive cues and expectancy are eliminated by surgical anesthesia, ketamine does not show a statistically significant acute antidepressant effect over placebo, suggesting expectancy bias may drive substantial effect in standard unmasked or inadequately masked trials.
Limits
The sample size was small (n = 40) with wide confidence intervals that cross zero but do not exclude a potential effect. Follow-up was limited to 3 days, conducted at a single center, and confounded by surgical stress, recovery, and concurrent anesthetic agents.
Cited by
- supports A clinical trial administering ketamine versus placebo under surgical anesthesia to depressed patients showed that the antidepressant effect was predicted by the patients' belief that they received ketamine rather than actual drug administration.