Study Finds Esketamine Nasal Spray More Likely to Induce Remission in Treatment-Resistant MDD Than Quetiapine Extended Release

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A long-term clinical trial comparing esketamine CIII nasal spray with quetiapine extended release found that esketamine had greater success with inducing remission in participants with treatment-resistant major depressive disorder (MDD).

The clinical trial—a randomized, open-label, active-controlled, rater-blinded, phase 3b study called ESCAPE-TRD—aimed to evaluate the efficacy of flexibly dosed esketamine nasal spray (Johnson & Johnson’s Spravato) in comparison with the efficacy of quetiapine extended release, both when combined with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant MDD.¹

The primary end point of the study was remission, which the investigators defined as a score of 10 or lower on the Montgomery-Åsberg Depression Rating Scale (MADRS) at week 8, and the key secondary end point of the study was for participants not to relapse through week 32 after achieving remission at week 8.²

The investigators assigned 336 participants to the esketamine group and 340 participants to the quetiapine group. Upon analysis at week 8, they noted that more participants in the esketamine group had achieved remission when compared with participants in the quetiapine group (91 of 336 participants [27.1%] vs 60 of 340 participants [17.6%]; P=0.003).²

They also noted that 73 of the 336 (21.7%) participants in the esketamine group experienced no relapse through week 32 after remission at week 8, compared with 48 of 340 (14.1%) participants in the quetiapine group.² Overall, the participants treated with esketamine nasal spray were 1.54 times as likely to reach remission at week 8 than the participants treated with quetiapine extended release.³

“Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray,” the investigators wrote. “The adverse events were consistent with the established safety profiles of the trial treatments.”²

Treatment-emergent adverse events were observed in 92% of participants treated with esketamine nasal spray and in 78% of participants treated with quetiapine extended release, and 4.2% of participants treated with esketamine nasal spray and 11% of patients treated with quetiapine extended release discontinued medication due to 1 or more adverse event(s).³

The results from ESCAPE-TRD were announced by Spravato (esketamine) developer Johnson & Johnson and published in The New England Journal of Medicine.⁴ The study published in The New England Journal of Medicine describes the full data gathered in ESCAPE-TRD for the first time.³

“This large head-to-head trial gives physicians important data to consider in the management of treatment-resistant depression by comparing the short- and long-term effectiveness of Spravato to an oral antipsychotic,” said Reina Benabou, MD, PhD, vice president of medical affairs, neuroscience, at Janssen Scientific Affairs, LLC, in a press release. “Spravato offers patients an additional important option. It is critical that those living with this difficult-to-treat condition have choices to consider for their personal treatment plans, in discussion with their health care providers.”³

Stay up-to-date on news related to research on promising new treatments for treatment-resistant major depressive disorder and a wide variety of other psychiatric disorders at psychiatrictimes.com.

References

1. 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). ClinicalTrials.gov. Updated February 15, 2023. Accessed October 5, 2023. https://www.clinicaltrials.gov/study/NCT04338321

2. Reif A, Bitter I, Buyze J, et al. Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med. 2023;389:1298-1309.

3. Large head-to-head study shows patients with treatment-resistant depression receiving Spravato (esketamine) CIII nasal spray were 1.54 times as likely to reach remission at 8 weeks than patients treated with quetiapine XR. Johnson & Johnson. News release. October 4, 2023. Accessed October 5, 2023. https://www.jnj.com/large-head-to-head-study-shows-patients-with-treatment-resistant-depression-receiving-spravato-esketamine-ciii-nasal-spray-were-1-54-times-as-likely-to-reach-remission-at-8-weeks-than-patients-treated-with-quetiapine-xr

4. Manalac T. J&J’s Spravato bests quetiapine in phase III head-to-head depression study. BioSpace. October 5, 2023. Accessed October 5, 2023. https://www.biospace.com/article/j-and-j-s-spravato-bests-quetiapine-in-phase-iii-head-to-head-depression-study-/