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)
ASPIRE II, a phase 3 double‑blind randomised trial, found that adjunctive esketamine 84 mg nasal spray produced a rapid and greater reduction in depressive symptoms than placebo plus standard care in adults with major depressive disorder and active suicidal ideation with intent, with significant differences at 4 and 24 hours (LS mean difference −3.9 at 24 h, P = .006). Both groups showed rapid improvement in clinician‑rated suicidality with no between‑group difference, and common esketamine adverse events included dizziness, dissociation, nausea and somnolence.
Authors
- Daniel Fu
- William Drevets
- Daniel Ionescu
Published
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.
Research Summary of '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)'
Introduction
Canuso and colleagues frame major depressive disorder (MDD) as a common, severe condition that frequently co-occurs with suicidal thoughts and behaviours, and they emphasise that people with active suicidal ideation with intent represent an especially ill subgroup with greater symptom severity, comorbidity, functional impairment and prior suicide attempts. Earlier research and clinical practice rely on hospitalisation and initiation or optimisation of oral antidepressants, but these traditional approaches have a delayed onset of full therapeutic effect (typically 4–6 weeks) and may be less effective in patients who present with suicidal intent. A small proof-of-concept trial suggested that esketamine nasal spray, an N-methyl-D-aspartate receptor antagonist, given with an oral antidepressant could produce rapid relief of depressive symptoms and suicidality, motivating larger confirmatory studies.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Ionescu, D. F., Fu, D., Qiu, X., Lane, R., Lim, P., Kasper, S., Hough, D., Drevets, W. C., Manji, H., & Canuso, C. M. (2021). 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). International Journal of Neuropsychopharmacology, 24(1), 22-31. https://doi.org/10.1093/ijnp/pyaa068
References (1)
Papers cited by this study that are also in Blossom
Ionescu, D. F., Lane, R., Lim, P. et al. · Journal of Clinical Psychiatry (2020)
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