Ketamine's effect on depression may hinge on hope: trial masks ketamine during surgery but both groups improve, suggesting expectancy matters

Ketamine's antidepressant effects may depend heavily on patient expectations, based on a randomized trial where participants were kept blind to whether they received ketamine. In the study, 40 people with moderate to severe depression were scheduled for routine surgery and received ketamine or placebo while under general anesthesia, with clinicians and researchers blinded during treatment. Two weeks later, both groups showed large improvements in depression severity soon after dosing. Because participants could not directly perceive ketamine effects during anesthesia, the pattern suggests psychological factors like hope and expectancy can drive much of the observed benefit. The findings also caution that ketamine is not simply a placebo, and they point to possible physiological links between placebo mechanisms and ketamine's action, such as involvement of brain opioid receptors.