Is Ketamine Nasal Spray a Breakthrough in Treating Treatment-Resistant Depression?
Recent clinical trials have shed light on the potential of esketamine, a derivative of ketamine, in the treatment of treatment-resistant major depression. Presented at the 36th ECNP Congress and published in the esteemed New England Journal of Medicine, these trials indicate that when combined with antidepressants, esketamine outperforms quetiapine in terms of remission rates. This development holds promise for individuals struggling with treatment-resistant depression, potentially expanding the pool of patients who can respond positively to treatment.
The Scope of Depression and Its Resistance
Clinical depression, often referred to as major depressive disorder (MDD), exerts a significant burden on society, both in terms of personal suffering and healthcare costs. Eurostat’s data from 2019 reveals that 7% of the European Union’s adult population experienced depression-related issues. Alarmingly, 20% to 30% of these individuals do not respond to conventional treatments. When patients fail to improve after two consecutive treatment regimens, they are classified as having treatment-resistant depression, a condition commonly seen among MDD patients receiving hospital care.
Exploring Treatment Options and Gaining New Insights
Quetiapine, an antipsychotic medication, is a frequently prescribed treatment for individuals with treatment-resistant depression, typically in combination with an antidepressant. However, esketamine nasal spray (NS) stands as the sole therapy specifically approved for treatment-resistant depression in Europe, often used in conjunction with other antidepressants. It received European approval in 2019.
The groundbreaking ESCAPE-TRD study marks the first large-scale investigation comparing the efficacy of esketamine and quetiapine. This research, sponsored by Janssen EMEA, the manufacturer of esketamine NS, represents a pivotal moment in the field.
Lead researcher Andreas Reif, hailing from Goethe University Frankfurt and the study’s first author, explains, “The ESCAPE-TRD trial was an open-label, single-blind, randomized, controlled trial, conducted across 171 sites comprising hospitals, inpatient and outpatient clinics, and research centers in 24 countries. This is the first trial to compare this new treatment with a standard existing treatment for treatment-resistant depression, and so it’s a really necessary study. The results are very positive.”
The study enrolled patients aged 18 to 74, all grappling with treatment-resistant depression, some of whom had seen no improvement after six prior treatment attempts. These individuals had been taking antidepressants, including selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs). Of the participants, 336 received esketamine nasal spray alongside an SSRI or SNRI, while another 340 were administered quetiapine in conjunction with an SSRI or SNRI. The treatment duration spanned eight weeks, followed by 24 weeks of maintenance therapy.
Professor Reif elaborates, “We were testing patients at two endpoints (goals). The first major endpoint was to understand the proportion of patients who achieved remission after eight weeks. The second was determining the proportion of patients who met the first endpoint and who were relapse-free at the end of the trial period (i.e., after 32 weeks). We measured the effects of treatment using a standard depression scale, the Montgomery‑Åsberg Depression Rating Scale.”
Results and Insights Revealed
At the eight-week mark, 28% of patients receiving esketamine plus antidepressants achieved remission, surpassing the 18% remission rate in the quetiapine group (primary endpoint). At the crucial 32-week juncture (key secondary endpoint), 22% of esketamine recipients remained in remission, in contrast to 14% of those who had taken quetiapine alongside antidepressants.
Lead researcher Professor Allan Young, from King’s College London, notes additional differences over time, stating, “For example, the patients receiving the esketamine treatment had fewer depressive symptoms than those taking quetiapine. We found that patients receiving esketamine NS were around 1.5 times as likely to experience remission at Week 8 than those receiving quetiapine XR.”
Moreover, patients treated with esketamine NS were 1.5 times more likely to achieve the key secondary endpoint, remaining relapse-free through Week 32. By Week 32, approximately half of patients receiving esketamine NS had achieved remission, with two-thirds demonstrating positive responses. This highlights the significance of continued treatment for those who do not initially attain remission.
Dr. Josep Antoni Ramos-Quiroga from Vall Hebron University Hospital (CIBERSAM) and Autonomous University of Barcelona, in an independent commentary, emphasized the superior response and safety profile of esketamine nasal spray compared to quetiapine. This revelation offers individuals with treatment-resistant depression a safer and more effective treatment option.
Concluding Thoughts
This research, presented during the ECNP New Medications symposium at the 36th ECNP Congress, has the potential to reshape the landscape of treatment-resistant depression. With over 5,300 participants, the ECNP Congress serves as Europe’s foremost platform for disseminating the latest advancements in disease-related neuroscience. Moreover, this groundbreaking work has been published in the prestigious New England Journal of Medicine.
In summary, esketamine nasal spray emerges as a promising avenue for individuals grappling with treatment-resistant depression, offering hope for a brighter future in mental health treatment.
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, 3 October 2023, New England Journal of Medicine. DOI: 10.1056/NEJMoa2304145. Funding: This study was funded by Janssen EMEA, manufacturers of esketamine NS.
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Frequently Asked Questions (FAQs) about Ketamine Nasal Spray
What is the main finding of the study on Esketamine Nasal Spray?
The main finding of the study is that Esketamine Nasal Spray, when combined with antidepressants, demonstrated better remission rates in patients with treatment-resistant major depression compared to quetiapine, a standard treatment.
How was the study conducted?
The study, known as the ESCAPE-TRD trial, was an open-label, single-blind, randomized, controlled trial conducted across 171 sites in 24 countries. It involved patients aged 18 to 74 with treatment-resistant depression who had previously tried multiple treatments, including antidepressants.
What were the key endpoints in the study?
The study assessed two main endpoints. The primary endpoint was to determine the proportion of patients achieving remission after eight weeks of treatment. The key secondary endpoint measured the proportion of patients who achieved remission at eight weeks and remained relapse-free at the end of the 32-week trial period.
What were the results of the study?
After eight weeks, 28% of patients receiving Esketamine Nasal Spray achieved remission, compared to 18% in the quetiapine group (primary endpoint). At 32 weeks, 22% of Esketamine Nasal Spray recipients were still in remission, as opposed to 14% in the quetiapine group (key secondary endpoint).
How does Esketamine Nasal Spray compare to other treatments for treatment-resistant depression?
Esketamine Nasal Spray is the only therapy specifically approved for treatment-resistant depression in Europe. This study demonstrated its superior efficacy when compared to quetiapine, a commonly used antipsychotic drug in treating this condition.
Who funded the study?
The study was funded by Janssen EMEA, the manufacturer of Esketamine Nasal Spray.
What are the implications of these findings for the treatment of treatment-resistant depression?
These findings offer hope to individuals with treatment-resistant depression, as Esketamine Nasal Spray shows promise as an effective and safe treatment option. It may expand treatment choices and improve outcomes for those who have struggled to respond to conventional therapies.
More about Ketamine Nasal Spray
- New England Journal of Medicine: “Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression”
- 36th ECNP Congress
- Eurostat: Share of people in EU reporting chronic depression, 2019
4 comments
i like dat they did dis study across so many countries. shows it’s a big deal.
i read the study in new england journal of medicine. the results r very interesting. esketamine seems promisin.
this is gr8 news 4 ppl who r suffering. quetiapine was gud but esketamine looks even better!
wow! dis study on Esketamine nasal spray is realy cool. it looks like it cud help lots of ppl with bad depression.