Importance Controlled studies have shown short-term efficacy of esketamine for treatment-
resistant depression (TRD), but long-term effects remain to be established. Objective To
assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an
oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in
patients with TRD in stable remission after an induction and optimization course of
esketamine nasal spray plus an oral antidepressant. Design, Setting, and Participants In this …