Skip to main content
SpringerLink
Log in

Intranasal esketamine in treatment-resistant depression: a profile of its use

  • Adis Drug Q&A
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

Intranasal esketamine (Spravato™), the S-enantiomer of ketamine, targets the glutamatergic system via non-competitive antagonism of the N-methyl-D-aspartate receptor, thereby providing a novel approach to traditional antidepressants that target modulation of the monoaminergic system. In conjunction with an oral antidepressant (OAD), intranasal esketamine is approved in the USA for use in adult patients with treatment-resistant depression (TRD). Given its novel mechanism and rapid onset of action, convenient weekly or once every 2 weeks maintenance regimen, and the current paucity of approved pharmacotherapy options for TRD, esketamine nasal spray in conjunction with an OAD provides an important treatment option for this difficult-to-treat high-risk patient population. In pivotal clinical trials in adult patients with TRD, flexible-dose intranasal esketamine in conjunction with a newly initiated OAD provided rapid and sustained improvements in depression symptoms, and had a manageable tolerability and safety profile. Further long-term clinical experience is required to fully define the potential benefits and risks of esketamine therapy in combination with an OAD in TRD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Cooper MD, Rosenblat JD, Cha DS, et al. Strategies to mitigate dissociative and psychotomimetic effects of ketamine in the treatment of major depressive episodes: a narrative review. World J Biol Psychiatry. 2017;18(6):410–23.

    Article  Google Scholar 

  2. Johnston KM, Powell LC, Anderson IA, et al. The burden of treatment-resistant depression: a systematic review of the economic and quality of life literature. J Affect Dis. 2019;24:195–210.

    Article  Google Scholar 

  3. Demyttenaere K, van Duppen Z. The impact of (the concept of) treatment-resistant depression: an opinion review. Int J Neuropsychopharm. 2019;22(2):85–92.

    Article  Google Scholar 

  4. Caraci F, Calabrese F, Molteni R, et al. International Union of Basic and Clinical Pharamcology CIV: the neurobiology of treatment-resistant depression—from antidepressant classifications to novel pharmacological targets. Pharmacol Rev. 2018;70:475–504.

    Article  CAS  Google Scholar 

  5. Amos TB, Tandon N, Lefebvre P, et al. Direct and indirect cost burden and change of employment status in treatment-resistant depression: a matched-cohort study using a US commercial claims database. J Clin Psychiatry. 2018;79(2):17m11725.

    Article  Google Scholar 

  6. Garay RP, Zarate CA Jr, Charpeaud T, et al. Investigational drugs in recent clinical trials for treatment-resistant depression. Expert Rev Neurother. 2017;17(6):593–609.

    Article  CAS  Google Scholar 

  7. Andrade C. Ketamine for depression, 3: does chirality matter? J Clin Psychiatry. 2017;78(6):e674–7.

    Article  Google Scholar 

  8. Spravato™ (esketamine) nasal spray, CIII: US prescribing information. Titusville (NJ): Janssen Pharmaceuticals, Inc.; 2019.

  9. Bahr R, Lopez A, Rey JA. Intranasal esketamine (Spravato™) for use in treatment-resistant depression in conjunction with an oral antidepressant. PT. 2019;44(6):340–75.

    Google Scholar 

  10. 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):411–20.

    Article  CAS  Google Scholar 

  11. 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 Neuropsychpharmacol. 2019. https://doi.org/10.1093/ijnp/pyz039.

    Article  Google Scholar 

  12. 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):428–38.

    Article  Google Scholar 

  13. Ochs-Ross R, Daly E, Zhang Y, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression [abstract no. P.533 + poster]. Eur Neuropyschopharmacol. 2019;29(Suppl 1):355–6.

    Article  Google Scholar 

  14. Shawi M, Alphs LD, Cooper K, et al. Clinical efficacy and safety of flexibly dosed intranasal esketamine in a U.S. population of patients with treatment-resistant depression [abstract no. 49]. In: 171st Annual Meeting of the American Psychiatric Association. 2018.

  15. Shawi M, Alphs LD, Popova V, et al. Clinical response, remission, and safety of flexibly dosed intranasal esketamine in a U.S. population of patients with treatment-resistant depression [abstract no. 50]. In: 171st Annual Meeting of the American Psychiatric Association. 2018.

  16. Ochs-Ross R, Daly EJ, Zhang Y, et al. Post hoc analyses of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression [abstract no. NR-6 + poster]. Am J Geriatric Psychiatry. 2019;27(3 Suppl):S140–1.

    Article  Google Scholar 

  17. Starr HL, Alphs LD, Ochs-Ross R, et al. Clinical efficacy and safety of intranasal esketamine in a U.S. population of geriatric patients with treatment-resistant depression [abstract no. 52]. In: 171st Annual Meeting of the American Psychiatric Association. 2018.

  18. Starr HL, Alphs LD, Ochs-Ross R, et al. Clinical response, remission, and safety of intranasal esketamine in a U.S. population of geriatric patients with treatment-resistant depression [abstract no. 51]. In: 171st Annual Meeting of the American Psychiatric Association. 2018.

  19. 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. https://doi.org/10.1001/jamapsychiatry.2019.1189.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wajs E, Leah A, Morrision R, et al. Long-term safety of esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: SUSTAIN-2 phase 3 study [abstract no. P.012 + poster]. Eur Neuropsychopharmacol. 2019;29(Suppl 1):s44–5.

    Article  Google Scholar 

  21. Nijs M, Wajs E, Aluisio L, et al. Managing esketamine treatment frequency toward successful outcomes: analysis of phase 3 data [poster no. P8-030]. In: Annual Meeting of the American Psychiatric Association; 2019.

  22. Aluisio L, Wajs E, DiBernardo A, et al. Withdrawal symptom assessment - intranasal esketamine: open-label safety study in treatment-resistant depression [poster no. 132]. In: American Society of Clinical Pathology Meeting: 2019.

  23. Morrison RL, Fedgchin M, Singh J, et al. Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study. Psychopharmacology. 2018;235(4):1107–19.

    Article  CAS  Google Scholar 

  24. Fua S, Gogate J, Starr L, et al. The relationship between adverse event reporting and events identified by scales/vital sign measurement with esketamine nasal spray plus an oral antidepressant in treatment-resistant depression (SUSTAIN-2 Study) [abstract + poster]. In: International Society for CNS Clinical Trials and Methodology (ISCTM) 15th Annual Scientific Meeting; 2019.

  25. 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):139–48.

    Article  Google Scholar 

  26. Doherty T, Wajs E, Melkote R, et al. Cardiac safety of esketamine nasal spray in treatment-resistant depression: results from the clinical development program [poster no. P8-031]. In: 172nd Annual Meeting of the American Psychiatric Association: 2019.

  27. van de Loo A, Bervoets AC, Mooren L, et al. Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study. Psychopharmacology. 2017;234(21):3175–83.

    Article  Google Scholar 

  28. Hernandez LG, Li S, Toro-Diaz H, et al. Cost-effectiveness analysis of esketamine in treatment-resistant depression in the United States [abstract no. PMH19 + poster]. Value Health. 2019;22(Suppl 1).

  29. Le HH, Zhang Q, Sheehan J. Budget impact analysis of esketamine in treatment-resistant depression in the United States [abstract no. PMH23 + poster]. Value Health. 2019;22(Suppl 1).

Download references

Acknowledgements

The manuscript was reviewed by: S. Kasper, Department of General Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; A. Winkour. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA. During the peer review process, Janssen Pharmaceuticals Inc., the marketing-authorization holder of esketamine, was offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Lesley J. Scott

Authors
  1. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lesley J. Scott.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflicts of interest

Lesley Scott is an employee of Adis International Ltd./Springer Nature, is responsible for the article content and declares no conflicts of interest.

Additional information

Enhanced material for this Adis Drug Q&A can be found at https://doi.org/10.6084/m9.figshare.9866693.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scott, L.J. Intranasal esketamine in treatment-resistant depression: a profile of its use. Drugs Ther Perspect 35, 536–545 (2019). https://doi.org/10.1007/s40267-019-00675-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40267-019-00675-z

Search

Navigation