Esketamine Nasal Spray: A Revolutionary Approach for Treating Resistant Depression

by Amir Hussein
Esketamine Nasal Spray for Treatment-Resistant Depression

Esketamine Nasal Spray demonstrated superior efficacy to standard treatments in a significant clinical study, achieving a 28% remission rate in treatment-resistant depression (TRD) patients over an eight-week period, compared to 18% for those treated with quetiapine. The study was sponsored by Janssen Pharmaceutica NV.

Treatment-resistant depression represents an especially difficult subtype of major depressive disorder. As articulated by Albino Oliveira-Maia, the head of the Champalimaud Foundation’s Neuropsychiatry Unit and the Portuguese national coordinator of the study, “TRD is characterized by the continued presence of depressive symptoms despite adequate administration of at least two distinct antidepressants.” For these patients, traditional therapies have proven ineffective.

The challenge posed by TRD is considerable. Research from the National Institute of Mental Health (NIMH) has shown that while one-third of depression patients achieve remission with their first course of treatment, successive treatments have increasingly less effectiveness—only 10-15% of patients find remission after their third round of therapy. This makes the quest for more effective treatment methods all the more urgent.

A Potential Breakthrough: Esketamine for TRD

Janssen’s esketamine nasal spray is a ketamine derivative that has consistently outperformed placebo in various clinical studies. The medication has received approval from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Oliveira-Maia emphasizes, “There is a shortage of medications specifically targeted at TRD. Moreover, in order to be considered for inclusion in healthcare policies and insurance plans, pharmaceutical companies must prove that their drug offers a unique benefit over existing therapies. This forms the basis for the current study.”

Comparative Analysis: Esketamine and Quetiapine

The investigation compared the effectiveness of esketamine nasal spray with oral quetiapine XR, an atypical antipsychotic initially designed for conditions like schizophrenia but also approved as an adjunctive therapy for certain depressive disorders. Designed to simulate real-world conditions, the study was not double-blinded due to the acute dissociative effects associated with esketamine. However, independent raters blinded to treatment allocations performed efficacy assessments. Over 800 patients were screened for the study, and more than 600, who met stringent TRD criteria, participated.

Patients were divided into two groups: one group self-administered quetiapine XR at home, while the other was treated with esketamine nasal spray in a hospital setting. Both groups maintained their previous antidepressant regimen, whether it was a selective serotonin reuptake inhibitor (SSRI, such as fluoxetine) or a serotonin and norepinephrine reuptake inhibitor (SNRI, such as venlafaxine). “The duration of the study, at 32 weeks, was longer than most similar trials, allowing us to evaluate both short- and long-term outcomes,” Oliveira-Maia noted.

The objective was to assess whether esketamine-treated patients were more likely to achieve remission within eight weeks compared to those on quetiapine. The study also aimed to evaluate the maintenance of remission rates throughout the 32-week period.

Key Findings Unveiled

The study revealed that after eight weeks, 27.1% of patients treated with esketamine reached remission, compared to 17.6% treated with quetiapine. For patients who maintained remission through 32 weeks, the numbers stood at 21.7% for the esketamine group and 14.1% for the quetiapine group.

“What is particularly noteworthy is the increase in remission rates beyond the initial eight-week period,” stated Oliveira-Maia. He explained that if the study had concluded at that point, the findings would be intriguing but not necessarily groundbreaking.

Safety and Future Considerations

Both medications were associated with a low incidence of severe adverse events. However, esketamine exhibited a higher frequency of less serious side effects, which was expected given its dissociative properties. Importantly, fewer patients discontinued esketamine due to adverse effects compared to quetiapine, suggesting better overall tolerability.

Moving Forward: Implications and Next Steps

The outcomes offer hope for TRD patients, but as Oliveira-Maia emphasizes, “Translating this research into policy is the real challenge. Accessibility to evidence-based therapies like esketamine remains limited in many countries, including Portugal.” Future research aims to identify predictive markers for treatment response, examine long-term remission rates, and consider the possible role of psychotherapy and other treatments like transcranial magnetic stimulation. According to Oliveira-Maia, both scientific advances and proactive policy initiatives are required to improve patient access to effective treatments.

Reference: “Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression” by Andreas Reif, Istvan Bitter, Jozefien Buyze, Kerstin Cebulla, Richard Frey, Dong-Jing Fu, Tetsuro Ito, Yerkebulan Kambarov, Pierre-Michel Llorca, Albino J. Oliveira-Maia, Thomas Messer, Siobhán Mulhern-Haughey, Benoît Rive, Christian von Holt, Allan H. Young and Yordan Godinov, published on October 3, 2023, in the New England Journal of Medicine.
DOI: 10.1056/NEJMoa2304145

Frequently Asked Questions (FAQs) about Esketamine Nasal Spray for Treatment-Resistant Depression

What is the main focus of the article?

The article primarily focuses on the effectiveness of esketamine nasal spray as a treatment for treatment-resistant depression (TRD). It presents findings from a pivotal clinical trial that compares esketamine with a standard treatment, quetiapine.

What is treatment-resistant depression (TRD)?

Treatment-resistant depression is a form of major depressive disorder characterized by the persistence of depressive symptoms despite multiple courses of standard antidepressant treatments.

Who conducted the clinical trial on esketamine nasal spray?

The clinical trial was conducted by Janssen Pharmaceutica NV and was coordinated in Portugal by Albino Oliveira-Maia, head of the Champalimaud Foundation’s Neuropsychiatry Unit.

What were the remission rates for patients using esketamine and quetiapine?

After eight weeks, 27.1% of patients using esketamine nasal spray achieved remission, compared to 17.6% using quetiapine. Long-term data showed 21.7% sustained remission in the esketamine group compared to 14.1% in the quetiapine group.

How long did the study last?

The study spanned 32 weeks, which allowed for both short-term and long-term assessment of treatment outcomes.

Were there any side effects noted for esketamine?

Yes, while both treatments recorded low rates of severe adverse events, patients in the esketamine group experienced a higher frequency of less serious side effects. Despite this, the rate of discontinuation due to side effects was lower for esketamine than for quetiapine.

What are the future directions for research in this area?

Future research aims to identify predictive markers for treatment responsiveness and to investigate ways to improve and sustain remission rates. The potential role of other treatments like psychotherapy and transcranial magnetic stimulation (TMS) is also being considered.

How does the study impact policy and access to treatment for TRD?

The study underscores the need for proactive policy measures to ensure that effective treatments like esketamine are accessible to patients suffering from TRD.

More about Esketamine Nasal Spray for Treatment-Resistant Depression

  • Clinical Trials on Treatment-Resistant Depression
  • National Institute of Mental Health Study on Depression Remission Rates
  • US Food and Drug Administration Approval for Esketamine
  • European Medicines Agency Approval for Esketamine
  • New England Journal of Medicine Publication on Esketamine vs. Quetiapine
  • Champalimaud Foundation’s Neuropsychiatry Unit
  • Overview of Quetiapine as an Antidepressant
  • Transcranial Magnetic Stimulation in Depression Treatment
  • Electroconvulsive Therapy in Depression Treatment

You may also like


Mike L. October 7, 2023 - 5:51 pm

gotta say, i’m impressed by the study’s thoroughness. 32 weeks is a long time to follow patients, gives the results more weight for sure. Great read.

Sarah K. October 7, 2023 - 10:37 pm

Really in-depth article, covers everything u need to know. it’s about time we got more effective treatments for depression. And the policy part, so important.

Daniel F. October 8, 2023 - 12:57 am

Very informative! But, man, shifting from research to policy is where the rubber meets the road. Hope governments take note.

Emily R. October 8, 2023 - 10:26 am

The part about future research really caught my eye. It’s not just about finding a treatment that works, but understanding why it works for some and not others.

James D. October 8, 2023 - 12:09 pm

Wow, this esketamine stuff seems like a game changer for people with TRD. I mean, the remission rates are way higher. But side effects though, hope they’re manageable.


Leave a Comment

* By using this form you agree with the storage and handling of your data by this website.

SciTechPost is a web resource dedicated to providing up-to-date information on the fast-paced world of science and technology. Our mission is to make science and technology accessible to everyone through our platform, by bringing together experts, innovators, and academics to share their knowledge and experience.


Subscribe my Newsletter for new blog posts, tips & new photos. Let's stay updated!

© 2023 SciTechPost