(esketamine)
This information is intended for US healthcare professionals to access current scientific information about Janssen products. It is prepared by Janssen Medical Information and is not intended for promotional purposes, nor to provide medical advice.
Last Updated: 06/21/2023
SPRAVATO nasal spray is available only through a restricted program under a REMS (Risk Evaluation and Mitigation Strategy) called the SPRAVATO REMS because of the risks of serious adverse outcomes from sedation, dissociation, and abuse and misuse.24
Singh et al (2023)11 conducted a comparative observational study in a real-world setting in patients with TRD (N=62) who had received either up to 6 IV ketamine infusions (0.5 mg/kg; n=47, 76%) or 8 SPRAVATO doses (56 mg/84 mg; n=15, 24%).
Nikayin et al (2022)12 conducted a comparative retrospective study for all Yale Interventional Psychiatric Service (IPS) patients (n=210) receiving 0.5 mg/kg IV ketamine over 40 min (n=129, 61.4%) or 56 mg or 84 mg SPRAVATO (n=81, 38.6%) between September 2016 and April 2021. Baseline demographics were balanced between groups. Adults with a major depressive episode receiving acute treatment (multiple treatments each ≤7 days apart for up to 8 total treatments) were included in the study.
Bahji et al (2022)12 conducted a meta-analysis of 36 randomized controlled trials (RCTs, parallel and crossover designs), spanning from 2000 through 2021, in adults with unipolar or bipolar depression with the primary objective of analyzing the efficacy and safety of racemic ketamine and esketamine.
The 36 RCTs included different routes of administration for both ketamine and esketamine, of which nine involved esketamine while the rest involved racemic ketamine. All studies used DSM criteria and most involved patients with MDD (n=33); 3 studies involved patients with bipolar depression. Most of these studies were focused on TRD (n=28). Subgroup analyses were also performed, which included an analysis by route of administration (IV vs. IN).
A literature search of MEDLINE®
1 | Daly EJ, Trivedi MH, Janik A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893-903. |
2 | Fedgchin M, Trivedi M, Daly E, 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. |
3 | 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. |
4 | 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. |
5 | Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891. |
6 | 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. |
7 | 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. |
8 | U.S. Food and Drug Administration. Center for Drug Evaluation and Research. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed June 14, 2023. |
9 | Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399-405. |
10 | Food and Drug Administration. FDA alerts health care professionals of potential risks associated with compounded ketamine nasal spray. https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-professionals-potential-risks-associated-compounded-ketamine-nasal-spray. Accessed June 14, 2023. |
11 | Singh B, Kung S, Pazdernik V, et al. Comparative effectiveness of intravenous ketamine and intranasal esketamine in clinical practice among patients with treatment-refractory depression: an observational study. J Clin Psychiatry. 2023;84(2):22m14548. |
12 | Nikayin S, Rhee TG, Cunninham ME, et al. Evaluation of the trajectory of depression severity with ketamine and esketamine treatment in a clinical setting. JAMA Psychiatry. 2022;79(7):736-738. |
13 | Bahji A, Zarate CA, Vazques GH. Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. Expert Opin Drug Saf. 2022;21(6):853-866. |
14 | Drug Enforcement Administration Diversion Control Division. Available at: https://www.deadiversion.usdoj.gov/schedules/index.html. Accessed June 14, 2023. |
15 | Center for Drug Evaluation and Research. Other Review. NDA 211243 - SPRAVATO (esketamine) - Reference ID: 4398871. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000OtherR.pdf. Published July 5, 2019. Accessed June 14, 2023. |
16 | Sanacora G, Zarate CA, Krystal JH, et al. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7(5):426-437. |
17 | Duman RS, Lin N, Liu RJ, et al. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 2012;62(1):35-41. |
18 | Duman RS, Aghajanian GK, Sanacora G, et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22(3):238-249. |
19 | Kim J, Farchione T, Potter A, et al. Esketamine for treatment-resistant depression - first FDA-approved antidepressant in a new class. N Eng J Med. 2019;381(1):1-4. |
20 | Zanos P Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23:801-811. |
21 | Kapur S, Seeman P. NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors - implications for models of schizophrenia. Mol Psychiatry. 2002;7:837-844. |
22 | Moaddel R, Abdrakhmanova G, Kozak J, et al. Sub-anesthetic concentrations of (R, S)-ketamine metabolites inhibit acetylcholine-evoked currents in alpha-7 nicotinic acetylcholine receptors. Eur J Pharmacol. 2013;698(1-3):228-234. |
23 | Ebert B, Mikkelsen S, Thorkildsen C, et al. Norketamine, the main metabolite of ketamine, is a non-competitive NMDA receptor antagonist in the rat cortex and spinal cord. Eur J Pharmacol. 1997;333:99-104. |
24 | SPRAVATO (esketamine nasal spray) [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf. |