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 and sustained improvements in depression symptoms.
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.
Synthesized
Comparable studies
Other non-randomized and open-label trials on esketamine for depression, most cited first.