Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II)
Dawn F. Ionescu, Dong-Jing Fu, Xin Qiu, Rosanne Lane, Pilar Lim, Siegfried Kasper, David Hough, Wayne C. Drevets, Husseini Manji, Carla M. Canuso
The International Journal of Neuropsychopharmacology August 26, 2020 DOI: 10.1093/ijnp/pyaa068 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 227 |
| Population | Adults aged 18-64 years with major depressive disorder and active suicidal ideation with intent |
| Interventions | Esketamine nasal spray Placebo nasal spray |
| Dose | 84 mg |
| Duration | 4-week double-blind treatment, with assessments at 4 hours and 24 hours post-first dose |
| Topics | Depression Esketamine |
| Keywords | Clinical global impression Placebo Randomized controlled trial Suicidal ideation Somnolence Adverse effect Poison control Injury prevention Cognition |
| Citations | 411 |
| Post-publication review | 1 comment on PubPeer (opens in new tab) · last active August 2023 |
| Registration | NCT03097133 |
| Key findings | Esketamine plus standard of care reduced depressive symptoms more than placebo plus standard of care at 24 hours in severely ill patients with MDD and active suicidal ideation. |
Abstract
Background: Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment.
Methods: This double-blind study (ASPIRE II) randomized adults (aged 18-64 years) with MDD having active suicidal ideation with intent to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks, given with comprehensive standard of care (hospitalization ≥5 days and newly initiated or optimized oral antidepressant[s]). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale total score (primary efficacy endpoint) was analyzed using ANCOVA. Clinical Global Impression-Severity of Suicidality-revised (key secondary endpoint) was analyzed using ANCOVA on ranks of change.
Results: Of 230 patients who were randomized (115 per arm), 227 received study drug and were included in efficacy/safety analyses; 184 (80.0%) completed double-blind treatment. Greater improvement in Montgomery-Asberg Depression Rating Scale total score was observed with esketamine (mean [SD]: -15.7 [11.56]) vs placebo (-12.4 [10.43]), each with standard of care, at 24 hours (least-squares mean difference [SE]: -3.9 [1.39], 95% CI: -6.60, -1.11; 2-sided P = .006). This was also noted at the earlier (4-hour) timepoint (least-squares mean difference -4.2, 95% CI: -6.38, -1.94). Patients in both treatment groups experienced rapid reduction in Clinical Global Impression-Severity of Suicidality-revised score; the between-group difference was not statistically significant. The most common adverse events among esketamine-treated patients were dizziness, dissociation, nausea, dysgeusia, somnolence, headache, and paresthesia.
Conclusion: This study confirmed rapid and robust reduction of depressive symptoms with esketamine nasal spray in severely ill patients with MDD who have active suicidal ideation with intent.
Trial Registration: Clinical Trials.gov identifier: NCT03097133.
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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Esketamine plus standard of care reduced depressive symptoms more than placebo plus standard of care at 24 hours, but the between-group difference in severity of suicidality was not significant.
Synthesized
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State of the evidence: Esketamine Supports
Esketamine plus standard of care reduced depressive symptoms more than placebo plus standard of care at 24 hours in severely ill patients with MDD and active suicidal ideation.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.