Rapidity of Symptom Improvement With Intranasal Esketamine for Major Depressive Disorder: A Systematic Review and Meta-Analysis

Rebecca S. Hock, PhD; Anna Feeney, MD; Nadia Iovieno, MD; James W. Murrough, MD, PhD; Sanjay J. Mathew, MD; Dan V. Iosifescu, MD; Maurizio Fava, MD; Manish K. Jha, MD; George I. Papakostas, MD

J Clin Psychiatry 2023;84(1):21r14086

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Author Affiliations

Clinical Trials Network and Institute, Department of Psychiatry, Massachusetts General Hospital; and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Equal contribution.
Corresponding author: Rebecca S. Hock, PhD, 1 Bowdoin Sq, 9th Floor, Boston, MA 02114 ([email protected]).
Clinical Trials Network and Institute, Department of Psychiatry, Massachusetts General Hospital; and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Equal contribution.
Clinical Trials Network and Institute, Department of Psychiatry, Massachusetts General Hospital; and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry; and Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, and Michael E. Debakey VA Medical Center Mental Health Care Line, Houston, Texas
Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg; and Department of Psychiatry, New York University School of Medicine, New York, New York
Clinical Trials Network and Institute, Department of Psychiatry, Massachusetts General Hospital; and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas
Clinical Trials Network and Institute, Department of Psychiatry, Massachusetts General Hospital; and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts

References (25)

GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211–1259. PubMed CrossRef
Papakostas GI, Jackson WC, Rafeyan R, et al. Inadequate response to antidepressant treatment in major depressive disorder. J Clin Psychiatry. 2020;81(3):OT19037COM5. PubMed CrossRef
Papakostas GI, Jackson WC, Rafeyan R, et al. Overcoming challenges to treat inadequate response in major depressive disorder. J Clin Psychiatry. 2020;81(3):OT19037BR4. PubMed CrossRef
Rafeyan R, Papakostas GI, Jackson WC, et al. Inadequate response to treatment in major depressive disorder: augmentation and adjunctive strategies. J Clin Psychiatry. 2020;81(3):OT19037BR3. PubMed CrossRef
Jackson WC, Papakostas GI, Rafeyan R, et al. Recognizing inadequate response in patients with major depressive disorder. J Clin Psychiatry. 2020;81(3):OT19037BR2. PubMed CrossRef
Trivedi MH, Papakostas GI, Jackson WC, et al. Implementing measurement-based care to determine and treat inadequate response. J Clin Psychiatry. 2020;81(3):OT19037BR1. PubMed CrossRef
Ionescu DF, Papakostas GI. Current trends in identifying rapidly acting treatments for depression. Curr Behav Neurosci Rep. 2016;3(2):185–191. PubMed CrossRef
Fava M, Freeman MP, Flynn M, et al. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020;25(7):1592–1603. PubMed CrossRef
Singh JB, Fedgchin M, Daly E, et al. Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol Psychiatry. 2016;80(6):424–431. PubMed CrossRef
Singh JB, Daly EJ, Mathews M, et al. Approval of esketamine for treatment-resistant depression. Lancet Psychiatry. 2020;7(3):232–235. PubMed CrossRef
Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616–630. PubMed CrossRef
Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428–438. PubMed CrossRef
Papakostas GI, Salloum NC, Hock RS, et al. Efficacy of esketamine augmentation in major depressive disorder: a meta-analysis. J Clin Psychiatry. 2020;81(4):19r12889. PubMed CrossRef
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. PubMed CrossRef
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134(4):382–389. PubMed CrossRef
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. PubMed CrossRef
StataCorp. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC; 2017.
Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018;75(2):139–148. PubMed CrossRef
Ochs-Ross R, Daly EJ, Zhang Y, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28(2):121–141. PubMed CrossRef
Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Focus Am Psychiatr Publ. 2019;17(1):55–65. PubMed CrossRef
Fu DJ, Ionescu DF, Li X, et al. 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). J Clin Psychiatry. 2020;81(3):19m13191. PubMed CrossRef
Ionescu DF, Fu DJ, Qiu X, et al. 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). Int J Neuropsychopharmacol. 2021;24(1):22–31. PubMed
A Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Participants with Treatment Resistant Depression. ClinicalTrials.gov. Accessed November 9, 2020. https://clinicaltrials.gov/ct2/show/NCT02918318
Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357–1366. PubMed CrossRef
Milak MS, Rashid R, Dong Z, et al. Assessment of relationship of ketamine dose with magnetic resonance spectroscopy of Glx and GABA responses in adults with major depression: a randomized clinical trial. JAMA Netw Open. 2020;3(8):e2013211. PubMed CrossRef