RCT · 2026
Adding CBT to esketamine for depression with suicidal thoughts: a randomized trial
- Original title
- Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention: The CBT-ENDURE Randomized Trial.
- Authors
- Wilkinson ST, Kitay BM, Macaluso M, et al.
- Journal
- The Journal of clinical psychiatry, 2026
- Molecules
- Esketamine
- Conditions
- Depression, Suicidal ideation
- Participants
- 93
- Evidence grade
- Moderate
- Source
- Read the original paper
The question
Can adding a course of cognitive behavioural therapy (CBT) to esketamine treatment help people with major depression and suicidal thoughts, and is such a study practical to run?
What they did
Ninety-three treatment-seeking people with major depressive disorder and suicidal ideation (57 in hospital, 36 outpatients) were randomly assigned to one of two groups. Both groups received esketamine, a nasal-spray form of ketamine, starting at 84 mg. One group also received 16 weeks of CBT, a structured talking therapy, delivered in one-on-one sessions plus a computer-assisted skills program; the other group received usual care alone. Enrolment ran from March 2021 to May 2025, and people were followed to week 18.
What they found
The trial met its main goal of feasibility: 93 people were randomized, reaching the recruitment target, and 72% completed the study, above the 70% retention goal. From baseline through week 18, the CBT group did better on three measures: the Beck Scale for Suicidal Ideation (mean difference -1.91, 95% CI -3.57 to -0.24, P=.025), a clinician-rated suicide severity scale (-0.33, 95% CI -0.58 to -0.08, P=.011), and the Montgomery-Åsberg Depression Rating Scale (-3.77, 95% CI -6.62 to -0.93, P=.009). There was no difference between groups on the Columbia-Suicide Severity Rating Scale, the suicidal-thoughts item of the MADRS, or in suicide-related events.
The fine print
The study’s main goal was feasibility, not effectiveness, so the symptom findings are secondary and should be treated as preliminary. The sample was modest and just over a quarter of participants did not complete the study. Results were inconsistent: some suicide measures favoured CBT while others showed no difference, and the average differences were small. Participants and therapists would have known who received CBT, follow-up ended at week 18, and this summary is based on the abstract alone.
What it means
Running a trial in people with depression and active suicidal thoughts proved practical, and adding CBT to esketamine showed modest additional benefit on some, but not all, measures of suicidal thinking and depression.
Evidence grade: Moderate. A randomized controlled trial, but modest in size, designed mainly to test feasibility, with mixed results across suicide measures.
This summary is based on the study’s published abstract.