Predicting Relapse in Treatment-Resistant Depression: Findings From New Esketamine Analysis

Leighann Forbes, MD, discussed post hoc analyses from the SUSTAIN-1 trial examining predictors of relapse following discontinuation of intranasal esketamine in patients with treatment-resistant depression (TRD).

Forbes emphasized the scale of the problem: approximately 280 million individuals are living with major depressive disorder (MDD). She emphasized that roughly 1 in 3 patients with depression do not respond to standard treatments, and that for those individuals, the clinical course is often characterized by partial improvement followed by relapse—a cycle with significant consequences for quality of life, relationships, and daily functioning.¹

The clinical context for the data was established by findings from the original SUSTAIN-1 trial, which demonstrated that continuing esketamine treatment was associated with approximately a 50% reduction in relapse risk compared with placebo in patients with TRD who had achieved stable remission. Forbes described the new post hoc analysis as addressing a highly practical clinical question: among patients who discontinue esketamine after achieving stability, which baseline characteristics confer the greatest relapse risk?² The analysis identified 3 key predictors: having failed at least 3 prior antidepressant trials, having a baseline severity rating of markedly ill, and having a history of suicidal behavior.

Forbes argued that these findings carry important implications for both patients and providers. She noted that "in treatment-resistant depression, getting better is really only the first step—helping patients stay well is where I think we can all make the biggest difference." She emphasized that identifying these high-risk characteristics should inform individualized, risk-stratified treatment decisions, and framed the data as a step toward more personalized care: "studies like this help move us towards more personalized care where a treatment decision can be based on a patient's individual risk of relapse."

Forbes concluded that durability of response was a critical and often underappreciated treatment goal in TRD, and that these data equipped clinicians to support not only short-term improvement but longer-term remission.

Dr Forbes is the vice president of US Medical Affairs for Neuroscience at Johnson & Johnson.

References

1. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-88.

2. Shleton R, Turkoz I, Dong-Jing F, et al. Esketamine nasal spray for relapse prevention in patients with treatment-resistant depression: a post-hoc analysis of predictors of relapse in placebo-treated patients in SUSTAIN-1 digital PLS. Accessed June 4, 2026. https://www.jnjmedicalconnect.com/therapeutic-areas/neuroscience/congress/ascp-2026/pls-esketamine-sustain-1