Esketamine Nasal Spray Shows Promise in Treating Stubborn Depression

In a breakthrough for those battling treatment-resistant depression, a study has indicated that esketamine nasal spray outperforms quetiapine extended-release. This finding offers new avenues for managing a condition notoriously difficult to treat.

Treatment-resistant depression (TRD) is a widespread issue, with approximately one-third of patients not responding to standard treatments such as SSRIs and SNRIs. TRD often leads to an increased risk of other health problems, higher suicide rates, and more frequent hospitalizations.

The high relapse rate in TRD patients underscores the urgent need for more effective treatments. In this context, Janssen Pharmaceutical Companies of Johnson & Johnson, in collaboration with University Hospital Frankfurt, conducted a Phase IIIb international randomized study. This study compared the effectiveness of two treatment regimens: one combining SSRI/SNRIs with esketamine nasal spray, and the other combining SSRI/SNRIs with quetiapine extended-release, as advised by the National Disease Management Guideline for Unipolar Depression.

The study revealed that esketamine nasal spray, when combined with SSRI/SNRIs, was more effective in achieving and maintaining remission in TRD patients.

Advantages of Esketamine

Professor Andreas Reif, the study’s principal investigator, explains that adding a non-antidepressant drug to existing SSRI or SNRI therapy can enhance their effectiveness. This approach was applied in the study, with quetiapine XR used alongside ongoing SSRI/SNRI treatment.

Esketamine, typically known for its analgesic properties in anesthesiology, exhibits significant antidepressant effects when administered via nasal spray. This impact is believed to counter reduced neuronal plasticity in the brain, a common trait in TRD patients.

The study found that 27.1% of patients treated with esketamine nasal spray, who had been suffering for over a year, achieved remission by Week 8. In contrast, only 17.6% of those treated with quetiapine extended-release reached remission in the same timeframe. Both groups were on concurrent SSRI/SNRI therapy.

Esketamine’s Continued Superiority

Esketamine nasal spray is already recognized as a potent antidepressant. Previous studies compared it with newly initiated SSRI/SNRI therapy against a placebo. These studies also noted esketamine’s significantly higher efficacy compared to the placebo.

In the New England Journal of Medicine-published study, esketamine nasal spray demonstrated 54% more effectiveness in inducing remission at Week 8 compared to quetiapine extended-release. This superiority was maintained in the six-month relapse rate evaluation.

ESCAPE-TRD Ph 3b Study Overview

The study, orchestrated by Janssen Pharmaceutical Companies of Johnson & Johnson and its Belgium affiliate, Janssen Pharmaceutica NV, involved extensive international collaboration. A total of 171 facilities across 24 countries, including hospitals, outpatient departments, and research centers, enrolled nearly 700 patients. The collaboration included the Department of Psychiatry, Psychosomatics and Psychotherapy at University Hospital Frankfurt and the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP in Frankfurt. The study’s goal was to compare the efficacy, safety, and tolerability of esketamine nasal spray against quetiapine extended-release in TRD patients, with esketamine showing more favorable results across all study endpoints.

Reference: “Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression” by Andreas Reif et al., 3 October 2023, New England Journal of Medicine. DOI: 10.1056/NEJMoa2304145.

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More about Esketamine Nasal Spray Depression Study

• Esketamine Nasal Spray Efficacy
• Treatment-Resistant Depression and Esketamine
• Janssen Pharmaceutical’s Role in Esketamine Study
• New England Journal of Medicine: Esketamine Study Results