Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression
Ewa Wajs, Leah Aluisio, Richard Holder, Ella Daly, Rosanne Lane, Pilar Lim, Joyce E. George, Randall L. Morrison, Gerard Sanacora, Allan H. Young, Siegfried Kasper, Ahmad Hatim Sulaiman, Cheng-Ta Li, Jong-Woo Paik, Husseini Manji, David Hough, Jennifer Grunfeld, Hong Jin Jeon, Samuel T. Wilkinson, Wayne C. Drevets, Jaskaran Singh
The Journal of Clinical Psychiatry April 20, 2020 DOI: 10.4088/jcp.19m12891 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase 3, open-label, multicenter, long-term study Peer reviewed |
|---|---|
| Sample size | 802 |
| Population | Adults (≥ 18 years) with treatment-resistant depression |
| Interventions | Esketamine nasal spray new oral antidepressant |
| Dose | 28-mg, 56-mg, or 84-mg |
| Duration | Up to 1 year (4-week induction phase and 48-week optimization/maintenance phase) |
| Topics | Depression Esketamine |
| Citations | 288 |
| Registration | NCT02497287 |
| Key points | Long-term esketamine nasal spray plus a new oral antidepressant had a manageable safety profile and sustained improvements in depression symptoms. |
Abstract
Objective: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD).
Methods: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.
Results: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).
Conclusions: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.
Trial Registration: ClinicalTrials.gov identifier: NCT02497287.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Long-term esketamine plus a new oral antidepressant had a manageable safety profile with sustained symptom improvements, though only about a quarter of those entering maintenance completed it.
Synthesized
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State of the evidence: Esketamine Supports
Long-term esketamine nasal spray plus a new oral antidepressant had a manageable safety profile and sustained improvements in depression symptoms, though only about a quarter of those entering the maintenance phase completed it.
Synthesized
Comparable studies
Other non-randomized and open-label trials on esketamine for depression, most cited first.
Citations in the library
Cited by 185
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Ketamine: A tale of two enantiomers Journal of Psychopharmacology November 6, 2020
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research May 1, 2022
- Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. The Lancet Psychiatry November 1, 2022
and 180 more in the library
Cites 3
- 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