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Esketamine linked to remission across six TRD clinical trials

Valerie A. Canady

Mental Health Weekly June 12, 2026 DOI: 10.1002/mhw.34908 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Clinical trial Peer reviewed
Population Patients with major depressive disorder, including those with treatment-resistant depression
Topics Depression Esketamine
Keywords Clinical trial Depression economics Depressive symptoms First line Pediatrics
Key findings By the third line of treatment, fewer than one in six patients with treatment-resistant depression achieved remission.

Abstract

For many patients with major depressive disorder, reaching remission — not just partial response — can significantly alter the course of illness, lowering the risk of relapse and improving day‐to‐day functioning. Yet that goal remains elusive for those with treatment‐resistant depression (TRD), where repeated medication failures, comorbid conditions, and lingering symptoms complicate care. Data from the STAR*D trial highlights the challenge that by the third line of treatment, fewer than one in six patients achieved remission.

Comparable studies

Other non-randomized and open-label trials on esketamine for depression, most cited first.

Study Year Design Participants
Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression 2020 Phase 3, open-label, multicenter, long-term study n = 802
Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Adults with treatment-resistant depression 2023 Open-label, long-term extension study n = 1,148
Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Adults with treatment-resistant depression who participated in ≥1 of 6 phase 3 parent... 2025 Open-label, single-arm long-term extension study n = 1,148
Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Patients with treatment-resistant major depressive disorder and comorbid post-traumatic... 2022 Open-label, single-arm, retrospective pilot study n = 11
Rapid and long-lasting effects of subcutaneous esketamine on suicidality: An open-label study in patients with treatment-resistant depression. Treatment-resistant depressive patients 2024 Open-label clinical trial n = 18

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