# Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study

Article · Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, Sanacora G, Wilkinson ST, Popova V, Fu DJ

- Archive id: doi:10.1038/s41386-023-01577-5
- Published: 2023-05-12
- Venue: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- DOI: https://doi.org/10.1038/s41386-023-01577-5
- PMID: 37173512
- PMCID: PMC10267177
- Citations: 107
- Source URL: https://doi.org/10.1038/s41386-023-01577-5
- PDF: https://europepmc.org/articles/PMC10267177/pdf
- Provenance: europepmc

## Abstract

Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3 "parent" studies could continue esketamine treatment, combined with an oral antidepressant, by enrolling in phase 3, open-label, long-term extension study, SUSTAIN-3. Based on their status at parent-study end, eligible participants entered a 4-week induction phase followed by an optimization/maintenance phase, or directly entered the optimization/maintenance phase of SUSTAIN-3. Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance. At the interim data cutoff (01 December 2020), 1148 participants were enrolled, 458 at induction and 690 at optimization/maintenance. Mean (median) cumulative duration of maintenance esketamine treatment was 31.5 (37.7) months (totaling 2769 cumulative patient-years). Common treatment-emergent adverse events (≥20%) were headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. Mean Montgomery-Åsberg Depression Rating Scale (MADRS) total score decreased during induction, and this reduction persisted during optimization/maintenance (mean \[SD\] change from the baseline to the endpoint of each phase: induction -12.8 \[9.73\]; optimization/maintenance +1.1 \[9.93\]), with 35.6% and 46.1% of participants in remission (MADRS total score ≤12) at induction and optimization/maintenance endpoints, respectively. Improvement in depression ratings generally persisted among participants who remained in maintenance treatment, and no new safety signal was identified during long-term treatment (up to 4.5 years) using intermittent-dosed esketamine in conjunction with daily antidepressant.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Novel Psychiatric Therapeutics](https://space-kitty.com/topics/psychiatric-therapeutics)

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