open access

Vol 18, No 4 (2021)
Review paper
Published online: 2021-06-24
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The significance of esketamine in treatment of treatment-resistant depression. Will it be a breakthrough drug?

Alicja Cichocka1, Emil Bartosz Rozenek1, Karolina Michałowska1, Bogumiła Szewczak2, Napoleon Waszkiewicz3
DOI: 10.5603/PSYCH.a2021.0026
·
Psychiatria 2021;18(4):289-298.
Affiliations
  1. Samodzielny Publiczny Zespół Zakładów Opieki Zdrowotnej w Wyszkowie, ul. Komisji Edukacji Narodowej 1, 07-200 Wyszków, Poland
  2. Uniwersytecki Szpital Kliniczny w Białymstoku, Marii Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
  3. Klinika Psychiatrii, Uniwersytet Medyczny w Białymstoku, Pl. Brodowicza 1, 16-070 Choroszcz, Poland

open access

Vol 18, No 4 (2021)
Prace poglądowe - nadesłane
Published online: 2021-06-24

Abstract

Esketamine opens a new chapter in treatment-resistant depression. It is used more and more often, because the therapeutic methods used so far do not provide fully satisfactory results. This article is a review of the most important information regarding the efficacy of esketamine and according to fighting depression and its influence on the glutamate system. The review also contains a short description of the most common adverse events, including the research of different stages of therapy on which they can appear. It turns out that appropriate influence on the glutamate system reduces symptoms of depression. Intranasal administration of esketamine quickly improves the condition of patients with treatment-resistant depression and reduces the risk of suicide. Long-term studies are still going on and their results should provide necessary information for improvement of this therapeutic method for treatment-resistant depression.

Abstract

Esketamine opens a new chapter in treatment-resistant depression. It is used more and more often, because the therapeutic methods used so far do not provide fully satisfactory results. This article is a review of the most important information regarding the efficacy of esketamine and according to fighting depression and its influence on the glutamate system. The review also contains a short description of the most common adverse events, including the research of different stages of therapy on which they can appear. It turns out that appropriate influence on the glutamate system reduces symptoms of depression. Intranasal administration of esketamine quickly improves the condition of patients with treatment-resistant depression and reduces the risk of suicide. Long-term studies are still going on and their results should provide necessary information for improvement of this therapeutic method for treatment-resistant depression.
Get Citation

Keywords

Esketamine; Ketamine; Major Depressive Disorder; S-Ketamine; Treatment-Resistant Depression; efficacy; safety

About this article
Title

The significance of esketamine in treatment of treatment-resistant depression. Will it be a breakthrough drug?

Journal

Psychiatria (Psychiatry)

Issue

Vol 18, No 4 (2021)

Article type

Review paper

Pages

289-298

Published online

2021-06-24

DOI

10.5603/PSYCH.a2021.0026

Bibliographic record

Psychiatria 2021;18(4):289-298.

Keywords

Esketamine
Ketamine
Major Depressive Disorder
S-Ketamine
Treatment-Resistant Depression
efficacy
safety

Authors

Alicja Cichocka
Emil Bartosz Rozenek
Karolina Michałowska
Bogumiła Szewczak
Napoleon Waszkiewicz

References (65)
  1. Gałecki P, Bliźniewska-Kowalska K. Treatment-resistant depression - recommendations of the National Consultant in the field of psychiatry. Psychiatria Polska. 2021; 55(1): 7–21.
  2. Eurostat. Household composition statistics. 2020; https://ec.europa.eu/eurostat/statistics-explained/index.php/Household_composition_statistics#More_and_more_households_consisting_of_adults_living_alone.
  3. Gałecki P, Szulc A. Psychiatria. Edra Uran & Partner, Wrocław 2016: 203.
  4. Pełka-Wysiecka J, Samochowiec J. Depresja – czy faktycznie zróżnicowana farmakoterapia? Psychiatria. 2014; 11(3): 141–147.
  5. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013; 34: 119–138.
  6. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012; 6: 369–388.
  7. Baethge C, Tondo L, Bratti IM, et al. Prophylaxis latency and outcome in bipolar disorders. Can J Psychiatry. 2003; 48(7): 449–457.
  8. Davis LL, Frazier E, Husain MM, et al. Substance use disorder comorbidity in major depressive disorder: a confirmatory analysis of the STAR*D cohort. Am J Addict. 2006; 15(4): 278–285.
  9. Peveler R, George C, Kinmonth AL, et al. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ. 1999; 319(7210): 612–615.
  10. 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.
  11. Lee PH, Perlis RH, Jung JY, et al. Multi-locus genome-wide association analysis supports the role of glutamatergic synaptic transmission in the etiology of major depressive disorder. Transl Psychiatry. 2012; 2: e184.
  12. Lener MS, Niciu MJ, Ballard ED, et al. Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine. Biol Psychiatry. 2017; 81(10): 886–897.
  13. Arnone D, Mumuni AN, Jauhar S, et al. Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol. 2015; 25(8): 1109–1117.
  14. Li CT, Chen MH, Lin WC, et al. The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study. Hum Brain Mapp. 2016; 37(3): 1080–1090.
  15. Moylan S, Maes M, Wray NR, et al. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry. 2013; 18(5): 595–606.
  16. Ignácio ZM, Réus GZ, Arent CO, et al. New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br J Clin Pharmacol. 2016; 82(5): 1280–1290.
  17. Newport DJ, Carpenter LL, McDonald WM, et al. APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015; 172(10): 950–966.
  18. Swainson J, Thomas RK, Archer S, et al. Esketamine for treatment resistant depression. Expert Rev Neurother. 2019; 19(10): 899–911.
  19. Himmelseher S, Pfenninger E. [The clinical use of S-(+)-ketamine--a determination of its place]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1998; 33(12): 764–770.
  20. Andrade C. Ketamine for Depression, 3: Does Chirality Matter? J Clin Psychiatry. 2017; 78(6): e674–e677.
  21. Domino EF, Warner DS. Anesthesiology. 2010; 113, 678–684. 2010.
  22. Singh JB, Fedgchin M, Daly EJ, et al. Relapse prevention in treatment-resistant major depressive disorder with rapid-acting antidepressants. Adv Pharmacol. 2020; 89: 237–259.
  23. 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.
  24. Palmer BA, Richardson EJ, Heesacker M, et al. Public Stigma and the Label of Gambling Disorder: Does it Make a Difference? J Gambl Stud. 2018; 34(4): 1281–1291.
  25. Ionescu DF, Fu DJ, Qiu 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): 22–31.
  26. 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.
  27. Khalifeh H, Hunt IM, Appleby L, et al. Suicide in perinatal and non-perinatal women in contact with psychiatric services: 15 year findings from a UK national inquiry. Lancet Psychiatry. 2016; 3(3): 233–242.
  28. Kanes S, Colquhoun H, Gunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017; 390(10093): 480–489.
  29. Machado C, Lacerda ALT, Bressan RA, et al. Esketamine for Postpartum Suicidality. Biol Psychiatry. 2021; 89(6): e35–e36.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 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).
  35. Murawiec S. Usłyszeć od pacjenta: „Darowała mi Pani kolejne życie” Wywiad z dr Jolantą Klemens. Psychiatria. 2021; 18(2): 159–162.
  36. Tiller J. Depression and anxiety. Medical Journal of Australia. 2013; 199(S6).
  37. Lara DR, Bisol LW, Munari LR. Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine in refractory unipolar and bipolar depression. Int J Neuropsychopharmacol. 2013; 16(9): 2111–2117.
  38. Esketamina - Charakterystyka Produktu Leczniczego.
  39. Wilkinson ST, Howard DH, Busch SH. Psychiatric Practice Patterns and Barriers to the Adoption of Esketamine. JAMA. 2019; 322(11): 1039–1040.
  40. Yanagihara Y, Ohtani M, Kariya S, et al. Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos. 2003; 24(1): 37–43.
  41. Li L, Vlisides PE. Ketamine: 50 Years of Modulating the Mind. Front Hum Neurosci. 2016; 10: 612.
  42. Chong C, Schug SA, Page-Sharp M, et al. Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009; 29(5): 317–324.
  43. Fanta S, Kinnunen M, Backman JT, et al. Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing. Eur J Clin Pharmacol. 2015; 71(4): 441–447.
  44. Lapidus KAB, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014; 76(12): 970–976.
  45. Janssen Pharmaceuticals. (2019). Spravato, ulotka dołączona do opakowania . https://www.janssenlabels.com/package-insert/productmonograph/prescribing-information/SPRAVATO-pi.pdf (2019).
  46. Bahr R, Lopez A, Rey JA. Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant. PT 2019; 44(6): 340-375.
  47. Pereira S, Brennan E, Patel A, et al. Managing dissociative symptoms following the use of esketamine nasal spray: a case report. Int Clin Psychopharmacol. 2021; 36(1): 54–57.
  48. FDA report on esketamine for treatment resistant depression. 2019. https://www.fda.gov/media/121376/download.
  49. Shahani R, Streutker C, Dickson B, et al. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007; 69(5): 810–812.
  50. Tsai JH, Tsai KB, Jang MY. Ulcerative cystitis associated with ketamine. Am J Addict. 2008; 17(5): 453.
  51. van de Loo AJ, Bervoets AC, Mooren L, et al. The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2017; 234(21): 3175–3183.
  52. Folkerts HW, Michael N, Tölle R i wsp. Acta. Psychiatr. Scand. 1997; 96(5): 334-342.
  53. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet. 2003; 361(9360): 799–808.
  54. Berlim MT, McGirr A, Van den Eynde F, et al. Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual cingulate cortex for treatment-resistant depression: a systematic review and exploratory meta-analysis. J Affect Disord. 2014; 159: 31–38.
  55. Bajbouj M, Merkl A, Schlaepfer TE, et al. Two-year outcome of vagus nerve stimulation in treatment-resistant depression. J Clin Psychopharmacol. 2010; 30(3): 273–281.
  56. Martin JLR, Martín-Sánchez E. Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. Eur Psychiatry. 2012; 27(3): 147–155.
  57. Cao Xu, Deng C, Su X, et al. Response and Remission Rates Following High-Frequency vs. Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Over Right DLPFC for Treating Major Depressive Disorder (MDD): A Meta-Analysis of Randomized, Double-Blind Trials. Front Psychiatry. 2018; 9: 413.
  58. Senova S, Cotovio G, Pascual-Leone A, et al. Durability of antidepressant response to repetitive transcranial magnetic stimulation: Systematic review and meta-analysis. Brain Stimul. 2019; 12(1): 119–128.
  59. Schatzberg AF. A Word to the Wise About Intranasal Esketamine. Am J Psychiatry. 2019; 176(6): 422–424.
  60. Molero P, Ramos-Quiroga JA, Martin-Santos R, et al. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs. 2018; 32(5): 411–420.
  61. Muller J, Pentyala S, Dilger J, et al. Ketamine enantiomers in the rapid and sustained antidepressant effects. Ther Adv Psychopharmacol. 2016; 6(3): 185–192.
  62. Mynors-Wallis L, Gath D. Predictors of treatment outcome for major depression in primary care. Psychol Med. 1997; 27(3): 731–736.
  63. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012; 27(4): 215–223.
  64. Lenze EJ, Mulsant BH, Blumberger DM, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015; 386(10011): 2404–2412.
  65. Sackeim HA, Haskett RF, Mulsant BH, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA. 2001; 285(10): 1299–1307.

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