Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study.
Focus (American Psychiatric Publishing) April 1, 2026 Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
In an open-label extension study of adults with treatment-resistant depression, long-term intermittent intranasal esketamine combined with an oral antidepressant maintained improvements in depression ratings. Among 1,148 participants, mean Montgomery-Åsberg Depression Rating Scale scores decreased during the 4-week induction phase and remained stable during optimization/maintenance, with 35.6% and 46.1% of participants in remission at the respective endpoints. Common side effects included headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. No new safety signal emerged over up to 4.5 years of treatment, supporting sustained efficacy and tolerability for this population.