Six 4 week efficacy trials have now been published, of which only one reports a statistically significant difference between placebo nasal spray (and antidepressant) and esketamine (and antidepressant) on depression score at 4 weeks. There is debate about whether the 4.0 point difference found constitutes a clinically significant effect, 1 especially considering the large effect in the placebo plus antidepressant arm (15.8 points), possibly due to the hours of human contact involved. It is also

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... less than the 6.5 point difference Janssen used in their sample size calculation (p. 91 and p. 157 in Ref. 2). More importantly, the time point of 4 weeks in all these studies means the data are rather uninformative, since treatment-resistant depression is usually treated for months or years.