Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention

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 clinical trial evaluates the feasibility and efficacy of adjunctive cognitive behavioral therapy (CBT) with esketamine in patients with major depression and suicidal ideation (MDSI). criteria) and suicidal ideation were randomized (1:1) to receive esketamine plus a 16-week course of CBT or esketamine plus treatment as usual (TAU) alone. The starting dose of esketamine was 84 mg in both groups. The primary outcome was feasibility, with a key secondary outcome being improvement in suicidal ideation. CBT consisted of traditional one-on-one therapy sessions and a computer-assisted program to facilitate psychoeducation and attainment of skills. Enrollment occurred between March 2021 and May 2025. =.009). No difference between groups was observed in the Columbia-Suicide Severity Rating Scale score, MADRS-SI score, or suicide-related events. This study demonstrates the feasibility and the effectiveness of combining CBT with esketamine to reduce SI and prevent relapse in patients with MDSI. ClinicalTrials.gov identifier: NCT04760652.