Suicidal Ideation Effectiveness and Safety Outcomes from the Ketamine for Adult Depression Study (KADS).
Gregory Carter, Maree Hackett, Stevan Nikolin, Vanessa Dong, Nick Glozier, Shanthi Sarma, Donel Martin, Michael Berk, Verònica Gálvez-Ortiz, Andrew A Somogyi, Natalie T Mills, Sean Hood, Paul Glue, Bernhard Baune, Philip B Mitchell, Anthony Rodgers, Colleen Loo
Archives of suicide research : official journal of the International Academy for Suicide Research May 9, 2026 Peer reviewed DOI: 10.1080/13811118.2026.2669779 via PubMed
Summary
Ketamine showed beneficial effects on suicidal ideation scores in a study of adults with treatment-resistant depression. In cohort 2, there was a significant reduction in suicidal ideation as measured by the C-SSRS, while cohort 1 showed no significant differences. Mean baseline ideation scores were low (1.93 for cohort 1 and 2.0 for cohort 2). The findings suggest that future research should focus on suicidal ideation as a primary outcome.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 174 |
| Population | adults with treatment-resistant depression |
| Key finding | Cohort 2 had a significant reduction in suicidal ideation scores as measured by the C-SSRS. |
Abstract
Ketamine has disputed effects on suicidal ideation scores in depressed populations. This study assessed effectiveness of ketamine in adults with treatment resistant depression, examining a secondary outcome of suicidal ideation. Phase III, double-blind, randomized, active-controlled, multicenter trial. Participants were randomized to twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks; cohort 1 (n = 68) fixed-dose and cohort 2 (n = 106) flexible-dose. Analyses were cumulative link mixed models for change scores (baseline to treatment end), comparing ketamine versus midazolam (active control) for suicidal ideation, using the MADRS item 10 (planned) and C-SSRS (post hoc). Mean baseline ideation scores were low (MADRS-10 cohort 1: 1.93 and cohort 2: 2.0). Cohort 1 had no significant difference between intervention and control: MADRS-10 β = 0.97, (95% CI=-0.95 to 2.90, p = 0.32), C-SSRS β = 0.64, (95% CI=-1.27 to 2.55, p = 0.51). Cohort 2 had a non-significant reduction for MADRS-10: β -0.61 (95% CI=-1.65 to 0.44, p = 0.25), but a significant reduction for C-SSRS: β-1.32 (95% CI=-2.51 to -0.12, p = 0.03). Participants had a higher C-SSRS score than the previous session, each of which triggered a clinical review, in 13.8% of all treatment sessions. Subcutaneous, flexible-dosed, racemic ketamine over four weeks showed beneficial effects on suicidal ideation scores. Future studies should use suicidal ideation powered as a primary outcome, sample the full range of ideation scores, use consensus instruments, and explore treatment discontinuation, in various depressed populations.