Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I)
This placebo-controlled, double-blind study, phase 3 study (n=226) compared esketamine (84mg, nasal, 2xp/w for 4w) with a placebo spray and found esketamine to be effective in lowering depression scores (MADRS) for those suffering from depression (MDD) and suicidal ideation (SI). Scores on a measure of SI was, however, not significantly different between the two groups.
Authors
- Gerard Sanacora
- Daniel Fu
- William Drevets
Published
Abstract
Objective
To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation.
Methods
This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria, active suicidal ideation with intent, and need for psychiatric hospitalization. Patients were randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care treatment (initial psychiatric hospitalization and newly initiated or optimized oral antidepressant[s] therapy). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary endpoint) was analyzed using analysis of covariance (ANCOVA), and change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r; key secondary endpoint) score was analyzed using ANCOVA on ranks with treatment difference estimated using the Hodges-Lehmann estimate.
Results
Greater improvement in MADRS total score was observed with esketamine + standard-of-care versus placebo + standard-of-care at 24 hours (least-squares mean difference [SE]: −3.8 [1.39]; 95% CI, −6.56 to −1.09; 2-sided P = .006), as well as at earlier (4 hours) and later time points during 4-week double-blind treatment. The difference between groups in the severity of suicidality was not statistically significant (median of treatment difference [95% CI]: 0.0 [−1.00 to 0.00]; 2-sided P = .107). The most common adverse events among esketamine-treated patients were dizziness, dissociation, headache, nausea, and somnolence.
Conclusions
These findings demonstrate rapid and robust efficacy of esketamine nasal spray in reducing depressive symptoms in severely ill patients with major depressive disorder who have active suicidal ideation with intent.
Research Summary of 'Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I)'
Introduction
Depression is a common, disabling disorder that carries substantial suicide-related morbidity and mortality. Patients with major depressive disorder (MDD) who have active suicidal ideation with intent represent a particularly severe subgroup, with more pronounced depressive symptoms and poorer treatment response than those without suicidal ideation. Current standard management for such patients typically includes initiation or optimisation of oral antidepressants and inpatient care, but conventional antidepressants often take four or more weeks to reach full effect and there were, until recently, no approved pharmacological treatments specifically for rapid reduction of depressive symptoms in this high-risk population. Ionescu and colleagues describe a global clinical development programme comprising two identically designed Phase III trials (ASPIRE I and ASPIRE II) intended to test whether adding esketamine nasal spray to comprehensive standard of care produces a more rapid reduction in depressive symptoms than placebo plus standard of care. The study reported in this paper (identified in the text as ASPIRE II) set out to determine if esketamine plus standard of care would significantly reduce Montgomery–Åsberg Depression Rating Scale (MADRS) total score at 24 hours post first dose compared with placebo plus standard of care, and to characterise safety in this acutely suicidal population.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Fu, D., Ionescu, D. F., Li, X., Lane, R., Lim, P., Sanacora, G., Hough, D., Manji, H., Drevets, W. C., & Canuso, C. M. (2020). Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). The Journal of Clinical Psychiatry, 81(3). https://doi.org/10.4088/JCP.19m13191
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