Psychiatrist.comCognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention: The CBT-ENDURE Randomized Trial

⚠️ Small Study / Early Comparative Evidence
The CBT-ENDURE randomized trial enrolled 93 patients with major depression and suicidal ideation across inpatient and outpatient settings, comparing esketamine plus 16 weeks of CBT against esketamine plus treatment as usual. The trial met its primary feasibility endpoints and reported favorable secondary outcomes on select ideation and depression scales.

Clinical Considerations

• Feasibility benchmarks were met with 80% enrollment and 72% retention through week 18.
• CBT group showed greater reductions on BSSI, CGI-S, and MADRS scores versus TAU at week 18, with mean differences statistically significant but modest in magnitude.
• No between-group difference emerged on the Columbia-Suicide Severity Rating Scale, MADRS suicidal ideation item, or suicide-related events.
• Mixed scale-level results and the small sample limit confident inference about ideation-specific benefit beyond general depressive symptom improvement.

Practice Applications

• Recognize structured CBT as a reasonable adjunct following esketamine in patients with persistent depressive symptoms.
• Interpret ideation findings cautiously given divergent scale results and modest effect sizes.
• Monitor ideation using validated instruments regardless of acute-phase treatment response.
• Avoid generalizing feasibility-trial outcomes to broader effectiveness claims pending larger confirmatory trials.