Key Takeaways
- The cohort was highly ill and clinically relevant to inpatient psychiatry: 61.9% were enrolled while hospitalized, 45% had a lifetime suicide attempt, the mean MADRS was 39.0 (SD, 7.7), and the mean number of previous antidepressant failures was 3.9 (SD, 3.0).
- Benefit with adjunctive CBT was more apparent on multi-item or clinician-rated measures than on single-item or C-SSRS ideation ratings, with significant between-group differences for BSSI, composite MADRS, CGI improvement, and CGI severity, but not for the MADRS SI item or C-SSRS.
- The post-esketamine acute response was modest despite severe baseline illness: from baseline to week 5, mean MADRS change was −14.1 points (SD = 11.1), with response and remission rates of 26.5% and 10.8%, supporting the need for a continuation strategy after the 4-week index course.
- CBT engagement was strong in this high-risk population, with an overall completion rate of all CBT sessions of 80.7% and completion of the 9 computer-assisted CBT modules of 76.7%, suggesting that structured psychotherapy can be delivered even during the transition from acute treatment to outpatient follow-up.
- Process measures confirmed that patients actually acquired CBT skills: CTAS scores were 2.24 points better at week 18 (95% CI, 0.63 to 3.84; P = .006) and 3.16 points at week 26 (95% CI, 1.31 to 5.01; P = .001), while SoCT scores were 2.59 points higher at week 18 (95% CI, 0.02 to 5.17; P = .048) and 5.48 points at week 26 (95% CI, 2.47 to 8.48; P = .001).
- Event-driven suicide outcomes were uncommon enough that this trial could not separate groups, but the event pattern was clinically informative: 14/19 suicide-related events occurred in patients hospitalized at enrollment, and the authors estimate that a trial powered for a moderate treatment effect would need 200–300 participants recruited from hospitals or similar settings.
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Do not stop treatment planning at the end of the 4-week esketamine index course; acute benefit was modest, with a mean MADRS change of −14.1 points (SD = 11.1), a response rate of 26.5%, and a remission rate of 10.8% at week 5.
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If you are tracking suicidal ideation after esketamine, use more than the C-SSRS ideation subscale; CBT separated from TAU on BSSI at week 18 (−6.01 vs −4.10; mean difference of −1.91, 95% CI, −3.57 to −0.24, P=.025) but not on the C-SSRS (−0.80 vs −0.93; group difference 0.13, 95% CI −0.39 to 0.65, P=.623).
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A structured 16-week CBT course is deliverable even in patients with MDSI during and after esketamine treatment; 72/93 (77.4%) were retained through week 18, CBT session completion was 80.7%, and completion of the 9 computer-assisted modules was 76.7%.
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When designing or interpreting suicide-focused trials, remember that risk clusters in hospitalized patients; 14/19 suicide-related events occurred in those hospitalized at enrollment, and the authors estimate that detecting a moderate treatment effect would require 200–300 participants from hospitals or similar settings.
