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COGNITIVE BEHAVIORAL THERAPY FOLLOWING ESKETAMINE FOR MAJOR DEPRESSION AND SUICIDAL IDEATION FOR RELAPSE PREVENTION: THE CBT-ENDURE STUDY

Samuel Wilkinson — Yale School of Medicine

2026 ASCP Annual Meeting

Objective

Suicide is a public health crisis in the US, with limited evidence demonstrating efficacy of treatments for high-risk patients due in part to their exclusion from most clinical trials. This study evaluates the feasibility of the adjunctive use of cognitive behavioral therapy (CBT) to esketamine in patients with major depression and suicidal ideation (MDSI).

Methods

Treatment-seeking patients (57 inpatients; 36 outpatients) with MDSI were randomized to receive esketamine plus a 16-week course of CBT or esketamine plus treatment as usual alone (TAU). The primary outcome was feasibility, with a key secondary outcome being improvement in suicidal ideation.

Results

93 subjects were randomized with a 72% study completion rate, demonstrating feasibility (primary outcome) by meeting recruitment goals of 80% of targeted enrollment and 70% of retention through study endpoint. Change in suicidal ideation from baseline through week 26 (a key secondary outcome), based on the Beck Scale for Suicidal Ideation (BSSI), Clinician Global Improvement Scale for Suicide Severity (CGI-S), MontgomeryAsberg Depression Rating Scale, Suicidal Ideation item (MADRS) favored the CBT group over the TAU group (BSSI mean difference of -1.91, 95% CI -3.57 to -0.24, p=0.025; CGI-S mean difference of -0.33, 95% CI -0.58 to -0.08, p=0.011; MADRS mean difference of -3.77, 95% CI -6.62 to -0.93, p=0.009). No difference between groups was observed in the CSSRS score, MADRS-SI score, or suicide-related events.

Conclusions

This study demonstrates the feasibility and potential effectiveness of combining CBT with esketamine to reduce suicidal ideation and prevent relapse in patients with MDSI.

References

  1. Cognitive behavioral therapy following esketamine for major depression and suicidal ideation for relapse prevention: The CBT-ENDURE randomized clinical trial study protocol. Kitay BM, Murphy E, Macaluso M, Corlett PR, Hershenberg R, Joormann J, Martinez -Kaigi V, Nikayin S, Rhee TG, Sanacora G, Shelton RC, Thase ME, Wilkinson ST. Psychiatry Res. 2023 Dec;330:115585.
  2. Beyond magic bullets: true innovation in health care. Narayan VA, Mohwinckel M, Pisano G, Yang M, Manji HK. Nat Rev Drug Discov. 2013 Feb;12(2):85-6.