How to Add CBT After Esketamine for Major Depression With Suicidal Ideation
How should clinicians structure adjunctive CBT after an acute esketamine course for patients with major depression and suicidal ideation?
Patients with major depression and suicidal ideation remain at high risk after the standard 4-week esketamine course, especially around hospitalization and discharge transitions. This trial addresses a practical continuation strategy by showing that a structured CBT program can be delivered during and after esketamine treatment and was associated with better longer-term outcomes than esketamine with treatment as usual alone.
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Confirm that the patient fits the studied population
Apply this workflow to treatment-seeking adults aged 18 to 65 years with major depression and suicidal ideation. In the trial, key exclusions were active substance use disorder within 6 months except tobacco, bipolar disorder, schizophrenia spectrum disorders, and cognitive disorders or intellectual disability that would impair meaningful engagement in CBT.
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Deliver the index esketamine course first
All participants received intranasal esketamine for 4 weeks, given twice per week according to clinical protocol and the FDA label for major depression with suicidal ideation. The initial dose was 84 mg, with later adjustment to 56 mg or 28 mg permitted for tolerability.
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Start CBT in week 3 while esketamine is still underway
Begin the psychotherapy phase in week 3 so that CBT overlaps with the last 2 weeks of the acute esketamine course. In the trial, this overlap was built into the intervention design rather than waiting until esketamine was fully completed.
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Provide a structured 16-week CBT course
Use a 16-week program combining individual and computerized CBT. The studied intervention included 16 to 20 face-to-face sessions plus 9 computerized lessons integrated across the 16 weeks.
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Use Beck-model CBT components and homework
Center sessions on psychoeducation, cognitive restructuring, behavioral activation, and changing schemas. Include homework such as thought records and activity charts, as these were part of the intervention actually delivered in the trial.
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Build each session around suicide-focused CBT routines
Start sessions with a mood check-in, set an agenda, and bridge from the prior session by reviewing homework. Incorporate specific attention to risk assessment, safety planning, and adaptation of CBT to suicide prevention throughout treatment.
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Allow ongoing maintenance esketamine if clinically indicated
After the acute 4-week esketamine course, additional esketamine was permitted in both groups based on physician judgment. This means the studied CBT strategy was adjunctive to real-world continuation care rather than dependent on abrupt discontinuation of esketamine.
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Track engagement through the full CBT period
Assess whether the patient is staying engaged through the 16-week course, since feasibility was a primary outcome of the trial. Among those assigned to CBT, overall completion of CBT sessions was 80.7% and completion of the 9 computerized modules was 76.7%, showing that this level of participation is achievable even in a high-risk sample.
Clinical Considerations
- The trial was not fully powered to provide definitive evidence on suicide-related events or all continuous outcomes.
- Patients could not be blinded to receiving additional therapy, so expectation effects may have contributed to between-group differences.
- The study included both inpatients and outpatients, and differences in overall intensity of care between these settings may have confounded results despite stratified randomization.
- The findings apply to patients able to engage meaningfully in CBT and do not directly address those with excluded comorbidities such as recent active substance use disorder, bipolar disorder, or schizophrenia spectrum disorders.
Bottom Line
When using esketamine for major depression with suicidal ideation, do not stop at the 4-week index course; begin a structured 16-week CBT program in week 3 and continue it as a relapse-prevention strategy.
