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 DOI: 10.1016/j.jad.2026.121181 via PubMed
Summary
AI-generated from the abstractRegulatory approvals for intranasal esketamine in treatment-resistant depression differ on its indication for suicidal ideation. In a two-center observational study of 261 adults with moderate-to-severe treatment-resistant depression, eight esketamine sessions over four weeks improved both depressive symptoms and suicidal ideation. However, after statistically adjusting for the antidepressant effect, the reduction in suicidal ideation was no longer significant. The findings suggest that esketamine's anti-suicidal effect does not persist independently of its antidepressant effect.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Sample size | 261 |
| Population | Adults with moderate-to-severe treatment-resistant depression at Sainte-Anne Hospital, Paris, France |
| Intervention | Intranasal esketamine |
| Duration | Eight esketamine sessions over four weeks |
| Topics | Depression Esketamine |
| Keywords | Suicide |
| 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.