Is there an independant anti-suicidal effect of esketamine in treatment resistant depression?
Michel Danon, Gabriela Ostronoff, Anne-cécile Petit, Pierre De Maricourt, Jakub M Kopeć, Lila Mekaoui, Lucie Berkovitch, Philip Gorwood
Journal of affective disorders May 1, 2026 Peer reviewed DOI: 10.1016/j.jad.2026.121181 via PubMed
Summary
Esketamine treatment for adults with moderate-to-severe treatment-resistant depression resulted in significant improvements in both depressive symptoms and suicidal ideation. However, the reduction in suicidal thoughts was not significant when accounting for overall mood improvement. In this study involving 261 participants over four weeks, both depressive and suicidal symptoms improved initially, but the anti-suicidal effect of esketamine appeared to depend on its antidepressant properties.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 261 |
| Population | adults with moderate-to-severe treatment-resistant depression |
| Key finding | The anti-suicidal effect of esketamine does not persist once its antidepressant effect is taken into account. |
Abstract
Regulatory approvals for intranasal esketamine in treatment-resistant depression (TRD) differ with respect to its indication for suicidal ideation. While rapid antidepressant effects are well documented, whether esketamine exerts an anti-suicidal effect independent of mood improvement remains unclear. In this two-center observational study, 261 adults with moderate-to-severe TRD at Sainte-Anne Hospital, Paris, France, received eight esketamine sessions over four weeks. MADRS-D (items 1-9) and MADRS-S (item 10) were rated before each session. Both MADRS-D (all p < .001) and MADRS-S (all p < .001) improved during esketamine treatment. In multivariate analysis, depressive improvement remained significant after adjusting for MADRS-S (all p < .001), whereas the reduction in suicidal ideation lost significance when adjusting for MADRS-D (all p > .949) in both samples. Our results suggest that the anti-suicidal effect of esketamine does not persist once its antidepressant effect is taken into account.