Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data
Michel Nijs, Ewa Wajs, Leah Aluisio, Ibrahim Turkoz, Ella Daly, Adam Janik, Stephane Borentain, Jaskaran Singh, Allitia DiBernardo, Frank Wiegand
The International Journal of Neuropsychopharmacology April 7, 2020 DOI: 10.1093/ijnp/pyaa027 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post-hoc analysis of an open-label, long-term study Peer reviewed |
|---|---|
| Sample size | 778 |
| Population | Patients with treatment-resistant depression |
| Interventions | Esketamine nasal spray oral antidepressant |
| Duration | Up to 1 year |
| Topics | Esketamine |
| Keywords | Phase matter |
| Citations | 21 |
| Registration | NCT02497287 |
| Key points | Adjusting esketamine treatment frequency based on symptom response can help maintain or improve clinical outcomes in patients with treatment-resistant depression. |
Abstract
Background: Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes.
Methods: This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During a 4-week induction phase, 778 patients self-administered esketamine twice weekly plus a new oral antidepressant daily. In responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale total score from baseline), esketamine treatment frequency was thereafter decreased during an optimization/maintenance phase to weekly for 4 weeks and then adjusted to the lowest frequency (weekly or every other week) that maintained remission (Montgomery-Åsberg Depression Rating Scale ≤ 12) based on a study-defined algorithm. The relationship between treatment frequency and symptom response, based on clinically meaningful change in Clinical Global Impression-Severity score, was subsequently evaluated 4 weeks after treatment frequency adjustments in the optimization/maintenance phase.
Results: Among 580 responders treated with weekly esketamine for the first 4 weeks in the optimization/maintenance phase (per protocol), 26% continued to improve, 50% maintained clinical benefit, and 24% worsened. Thereafter, when treatment frequency could be reduced from weekly to every other week, 19% further improved, 49% maintained benefit, and 32% worsened. For patients no longer in remission after treatment frequency reduction, an increase (every other week to weekly) resulted in 47% improved, 43% remained unchanged, and 10% worsened.
Conclusions: These findings support individualization of esketamine nasal spray treatment frequency to optimize treatment response in real-world clinical practice.
Trial Registration: ClinicalTrials.gov identifier: NCT02497287.
Comparable studies
Other non-randomized and open-label trials on esketamine, most cited first.
Citations in the library
Cited by 11
- Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance The World Journal of Biological Psychiatry November 3, 2020
- The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review Pharmaceutics December 22, 2023
- Esketamine in depression: putative biomarkers from clinical research. European Archives of Psychiatry and Clinical Neuroscience July 13, 2024
- A systematic review of ketamine and esketamine-induced long-term potentiation and synaptic scaling: Do the molecular and synaptic plasticity effects inform dosing intervals? Journal of Affective Disorders April 15, 2026
- Learning how to make use of dissociative therapies. International Review of Psychiatry December 1, 2024
and 6 more in the library
Cites 5
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020