Suicidality during intranasal (es)ketamine treatment: A retrospective cohort study.
Yamina Ehrt-Schäfer, Georgios Schoretsanitis, Erich Seifritz, Sebastian Olbrich, Stefano Ferrea
Journal of Affective Disorders October 21, 2026 DOI: 10.1016/j.jad.2026.122647 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective longitudinal cohort study Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Patients with treatment-resistant depression treated with intranasal (es)ketamine in routine care |
| Intervention | Intranasal (es)ketamine |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS) item 10, Beck-Depression-Inventory-II (BDI-II) item 9 |
| Topics | Depression Esketamine Ketamine |
| Keywords | Suicidality |
| Key findings | Mean suicidality ratings decreased modestly during intranasal (es)ketamine treatment, and upward and downward category transitions occurred at similar frequencies, with no evidence of treatment-phase-specific worsening. A minority of patients showed transient (38.8% MADRS, 21.3% BDI-II) or sustained (15.0% MADRS, 7.5% BDI-II) increases, and higher baseline suicidality was most consistently associated with later worsening. Two serious adverse events occurred, including one suicide. |
Abstract
Intranasal (es)ketamine has shown efficacy in therapy of treatment-resistant depression (TRD). However, its effects on suicidality have not been fully elucidated. We conducted a retrospective longitudinal cohort study of 80 patients affected by TRD, treated with intranasal (es)ketamine. Suicidality was assessed using item 10 of the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and item 9 of the Beck-Depression-Inventory-II (BDI-II). We measured patient- and transition-level fluctuations of suicidality, tested temporal clustering using mixed-effects logistic regression, examined associations between non-suicidal depressive symptom change and suicidality worsening, and explored baseline predictors. Mean suicidality ratings decreased modestly. Upward and downward category transitions occurred at similar frequencies across treatment (MADRS: 57 increases and 50 decreases across 767 valid transitions, 7.4% vs. 6.5%; BDI-II: 22 and 23 across 741 transitions, 3.0% vs. 3.1%). At least one upward transition occurred in 38.8% on MADRS and 21.3% on BDI-II. Transient elevations were more frequent than sustained elevations. Sustained elevation occurred at 15.0% on MADRS and 7.5% on BDI-II. Increases did not cluster by treatment phase. MADRS, but not BDI-II, upward transitions were associated with concurrent and lagged worsening in non-suicidal depressive symptoms. Higher baseline suicidality showed the most consistent association with later worsening across both measures. Two serious adverse events occurred, including one suicide. In this routine-care cohort, suicidality decreased on average, with no evidence of treatment-phase-specific worsening. Nonetheless a minority of patients showed transient or, less often, sustained increases in suicidality, supporting necessity of continuous suicidality monitoring throughout (es)ketamine treatment.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cites 27
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Journal of Psychiatric Research December 11, 2020
and 22 more in the library