Benefit–Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment‐Resistant Depression

Adding esketamine nasal spray to an oral antidepressant improves outcomes for people with treatment-resistant depression. During the initial treatment phase, for every 100 patients, 5 to 21 more achieve remission and 14 to 17 more show a response compared to those receiving a placebo plus an antidepressant. In maintenance therapy, 19 to 32 fewer relapses occur with esketamine. Serious or severe side effects—mainly dissociation, vertigo, and dizziness—differ little between the groups. The findings indicate a favorable balance of benefits and risks for esketamine combined with an antidepressant.

Study at a glance

Abstract

This post hoc analysis assessed the benefit-risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment-resistant depression (TRD). The Benefit-Risk Action Team framework was utilized to assess the benefit-risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or responders in induction studies and proportion of stable remitters or stable responders who remained relapse-free in the maintenance study. Risks were death, suicidal ideation, most common adverse events (AEs), and potential long-term risks. Per 100 patients on esketamine + AD vs. AD + placebo in induction therapy, 5-21 additional patients would remit and 14-17 additional patients would respond. In maintenance therapy, 19-32 fewer relapses would occur with esketamine. In both cases, there was little difference in serious or severe common AEs (primarily dissociation, vertigo, and dizziness). These findings support a positive benefit-risk balance for esketamine + AD as induction and maintenance treatment in patients with TRD.