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).
Administration, Intranasal
Adolescent
Adult
Antidepressive Agents
/ administration & dosage
Depressive Disorder, Major
/ drug therapy
Double-Blind Method
Female
Humans
Ketamine
/ administration & dosage
Male
Middle Aged
Nasal Sprays
Outcome Assessment, Health Care
Patient Acuity
Suicidal Ideation
Young Adult
Esketamine
depression
suicidal ideation
suicide risk
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
20 01 2021
20 01 2021
Historique:
received:
07
04
2020
revised:
10
08
2020
accepted:
26
08
2020
pubmed:
30
8
2020
medline:
29
1
2022
entrez:
30
8
2020
Statut:
ppublish
Résumé
Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32861217
pii: 5899217
doi: 10.1093/ijnp/pyaa068
pmc: PMC7816667
doi:
Substances chimiques
Antidepressive Agents
0
Nasal Sprays
0
Esketamine
50LFG02TXD
Ketamine
690G0D6V8H
Banques de données
ClinicalTrials.gov
['NCT03097133']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22-31Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.
Références
J Clin Psychiatry. 2003 Sep;64(9):1094-100
pubmed: 14628986
J Trauma Stress. 1998 Jan;11(1):125-36
pubmed: 9479681
Br J Psychiatry. 2014 Dec;205(6):443-9
pubmed: 25213159
Depress Anxiety. 2016 Jun;33(6):483-94
pubmed: 26882201
Suicide Life Threat Behav. 2008 Oct;38(5):539-51
pubmed: 19014306
J Clin Psychopharmacol. 1990 Aug;10(4):244-51
pubmed: 2286697
Int J Neuropsychopharmacol. 2018 Jun 1;21(6):539-549
pubmed: 29860382
J Consult Clin Psychol. 2000 Jun;68(3):371-7
pubmed: 10883553
JAMA Psychiatry. 2018 Apr 1;75(4):336-346
pubmed: 29450462
BMJ Open. 2019 Mar 23;9(3):e023883
pubmed: 30904843
Science. 2012 Oct 5;338(6103):68-72
pubmed: 23042884
Psychiatry Res. 2020 Jan 28;285:112810
pubmed: 32062326
Am J Psychiatry. 2007 Jul;164(7):1029-34
pubmed: 17606654
N Engl J Med. 2019 Jul 4;381(1):1-4
pubmed: 31116916
J Affect Disord. 1999 Oct;55(2-3):171-8
pubmed: 10628886
J Clin Psychiatry. 2020 May 12;81(3):
pubmed: 32412700
Psychiatry Res. 2020 Dec;294:113495
pubmed: 33068913
Am J Psychiatry. 2013 Jul;170(7):723-33
pubmed: 23318413
Am J Psychiatry. 2003 Nov;160(11 Suppl):1-60
pubmed: 14649920
Br J Psychiatry. 2008 Jan;192(1):52-8
pubmed: 18174510
Front Psychiatry. 2016 Jun 20;7:109
pubmed: 27378957
Am J Psychiatry. 2018 Jul 1;175(7):620-630
pubmed: 29656663
J Affect Disord. 2019 Feb 15;245:180-187
pubmed: 30396056
Am J Psychiatry. 2010 Jul;167(7):801-8
pubmed: 20478879
Eur Psychiatry. 2012 Feb;27(2):129-41
pubmed: 22137775
Crisis. 2011;32(6):319-33
pubmed: 21945840