SPRAVATO® for adults with treatment-resistant major depressive disorder

Findings presented at Royal College of Psychiatrists International Congress (RCPsych 2023) confirm the importance of SPRAVATO® as a therapeutic option for adults with treatment-resistant major depressive disorder in patients with 2 and >3 prior treatment failures.1

10 July 2023: The Janssen Pharmaceutical Companies of Johnson & Johnson announced further findings from the ESCAPE-TRD study. Data shows that treatment with esketamine nasal spray (NS) increased the likelihood of remission versus treatment with quetiapine extended release (XR) in sub-groups of treatment resistant depression (TRD) patients that had 2 and ≥3 prior treatment failures in the current episode.1 At Week 32, significantly more patients treated with esketamine NS vs quetiapine XR achieved remission in both sub-groups, 59.6% vs 41.3% in the group with 2 prior treatment failures (P≤0.001); 48.1% vs 29.8% in the group with ≥3 prior treatment failures (p<0.01). 1 Furthermore the time to remission was shortened with esketamine NS in both sub groups; patients with 2 and ≥3 prior treatment failures were respectively 1.5 ([1.21, 1.98]; p<0.001) and 2.0 times ([1.47, 2.91]; p<0.001) as likely to achieve remission at any timepoint versus quetiapine XR, when both were dosed as per their respective labels and used in combination with a continuing selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI). 1

The findings were presented at the Royal College of Psychiatrists International Congress (RCPsych 2023) 10 July to 13 July in Liverpool, United Kingdom, following earlier top line data from the study presented at the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) Congress last year, and further findings presented at the 31st European Congress of Psychiatry (EPA 2023) in March of this year.1,2,3 “We are excited that new treatments for depression are being developed, particularly for severe depression where patients have not responded to existing medications and other interventions,” says Marjorie Wallace, Chief Executive of SANE. “There has been a dearth of new ideas, which is why so many patients are given repeat prescriptions of drugs made available over 30 years ago. The only way forward is to encourage those in a position to do so to develop innovative treatments that may potentially transform the future of those whose suffering may drive them to debilitation and despair.” Approximately a third of people who experience major depressive disorder (MDD) do not respond to treatment and are considered to have TRD – a term for people living with MDD who have tried two or more antidepressant treatments without experiencing any relief.4,5 MDD and TRD can be serious and debilitating conditions and are much more common in the UK than people may think – MDD affects around one in five people in the UK at some point in their lives.6

“Patients who have experienced three or more prior treatment failures are typically less likely to respond to the current treatments available for TRD. These findings demonstrate the significant effect esketamine nasal spray has in patients living with the condition in both sub-groups, and an even greater relative effect in those with three or more prior treatment failures. This marks a major milestone in offering a potential treatment option that could improve quality of life for these individuals.

Professor Allan Young, Director, Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London

ESCAPE-TRD is a long-term, comparative, randomised, open-label, rater-blinded Phase IIIb clinical study designed to evaluate the short- and long-term efficacy, safety and tolerability of flexibly dosed esketamine NS compared with quetiapine XR, both in combination with a continuing SSRI or SNRI, in adults with TRD.2,7

“We are pleased to be presenting our latest data at RCPsych 2023 today. Our findings further inform us of the types of patients that may benefit the most from esketamine nasal spray and the potential positive effect it could have on their daily lives.” said Megan Walker, Therapeutic Area Medical Director, Neuroscience, Janssen-Cilag GmbH, part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Findings presented at RCPsych 2023 showed that the percentage of patients who achieved remission increased over time with either 2 or >3 prior treatment failures in both treatment options but was consistently higher in the esketamine NS treatment arm compared with quetiapine XR treatment arm.1 Esketamine NS was shown to demonstrate a superior remission rate in patients with >3 prior treatment failures, with patients 2.6 times as likely to achieve remission* at Week 8 versus quetiapine XR.1 At Week 8, 28.0% of patients treated with esketamine NS achieved remission compared to the 10.9% of patients being treated with quetiapine XR. 1

In addition, a significantly† greater proportion of patients with >3 prior treatment failures were relapse-free through Week 32 after remission at Week 8.1 Notably at Week 32, 18.2% of patients treated with esketamine NS were relapse-free after remission at Week 8 compared with 7.8% of patients treated with quetiapine XR. 1

Participants in the esketamine NS study arm with 2 prior treatment failures demonstrated a higher rate of remission at Week 8, compared with patients in the quetiapine XR study arm, 26.5% versus 21.8% respectively. 1 After remission at Week 8, 24.0% of patients in the esketamine NS study arm were relapse-free through Week 32 compared with the 18.0% of patients in the quetiapine XR treatment arm. 1

*Remission was defined as Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤10. MADRS is a clinician‐rated measure of depression severity.1

† Tested at a two-sided 0.05 significance level without adjustment for multiple testing. 1


1 Young AH. et al., Esketamine nasal spray improves rate and time to remission versus quetiapine extended release in subgroups of patients with treatment resistant depression and two or three plus prior treatment failures: Results from ESCAPE-TRD, a randomised phase IIIb trial. Presented at RCPsych 2023, July 10-13. Poster PO-424.
2 Reif A. et al., Esketamine nasal spray improves short‐ and long‐term outcomes compared with quetiapine extended release in patients with treatment resistant depression: First results from ESCAPE‐TRD, a randomised, multi‐centre phase IIIb clinical trial. Presented at DGPPN 2022, November 23-26. Poster P-01- 04.
3 Reif A. et al., Esketamine nasal spray shows higher remission and response rates over 32 weeks of treatment compared with quetiapine extended-release in patients with treatment resistant depression: Results from EXCAPE-TRD, a randomized, phase IIIb clinical trial. Presented at EPA 2023, March 25-28. Poster PO0067.
4 Ionescu DF, et al., Dialogues Clin Neurosci 2015;17(2):111–126. European Medicines Agency, 2013. Guideline on clinical investigation of medicinal products in the treatment of depression. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-depression_en.pdf. Last accessed: July 2023.
CP- 399452 July 2023
5 National Institute for Health and Care Excellence. Implanted vagus nerve stimulation for treatment-resistant depression. Available at: https://www.nice.org.uk/guidance/ipg679/resources/implanted-vagus-nerve-stimulation-for-treatmentresistant-depression-pdf-1899874293371845. Last accessed: July 2023.
6 Smith, D., et al., Prevalence and Characteristics of Probable Major Depression and Bipolar Disorder within UK Biobank: Cross-Sectional Study of 172,751 Participants. 2013. Plos ONE, 8(11), e75362. doi: 10.1371/journal.pone.0075362.
7 Clinicaltrials.gov. A long-term comparison of esketamine nasal spray versus quetiapine extended release, both in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor, in participants with treatment resistant major depressive disorder (ESCAPE-TRD). NCT 04338321.Available at: https://clinicaltrials.gov/ct2/show/NCT04338321?term=escape-trd&draw=2&rank=1. Last accessed: July 2023.
8 Mrazek DA, et al., A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014 Aug 1;65(8):977-87. doi: 10.1176/appi.ps.201300059.
9 Amos TB, 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 Mar/Apr;79(2):17m11725. doi: 10.4088/JCP.17m11725.
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11 Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp Clin Psychopharmacol. 2015 Feb;23(1):1-21. doi: 10.1037/a0038550.
12 Electronic Medicines Compendium. Spravato 28 mg nasal spray, solution. Available at: https://www.medicines.org.uk/emc/product/10977/smpc#gref. Last accessed: July 2023
13 Paul R, et al., Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. World J Biol Psychiatry. 2009;10(3):241-4. doi: 10.1080/15622970701714370.
14 European Medicines Agency. Summary of Product Characteristics. Spravato 28 mg nasal spray. Janssen Cilag International