Results from a major clinical trial have shown that esketamine outperforms one of the standard treatments for treatment-resistant major depression disorder (MDD).
Across the EU, 7% of the adult population was living with depression in 2019, with around 20 to 30% not responding to treatments. If a person does not respond to two treatments, they are classed as having treatment-resistant depression.
The antipsychotic drug quetiapine is commonly used in treatment-resistant depression, normally used together with an antidepressant. However, esketamine nasal spray is the only specifically approved therapy for treatment-resistant depression in Europe.
This new study – the ESCAPE-TRD study – describes the first large trial comparing esketamine with quetiapine and has been funded by Janssen EMEA, the manufacturers of esketamine nasal spray.
The industry-funded work is presented for the first time at the 36th ECNP Congress in Barcelona, with publication in the peer-reviewed journal the New England Journal of Medicine.
Study results
During the trial, patients who participated were between 18 and 74, all had treatment-resistant depression and all had been taking antidepressants, such as SSRI or SNRI.
A total of 336 patients received esketamine nasal spray plus an SSRI or SNRI, while another 340 patients received quetiapine plus an SSRI or SNRI. Both groups were treated for eight weeks, followed by 24 weeks of maintenance treatment.
After eight weeks, 28% of patients taking esketamine plus antidepressants achieved remission, compared to 18% remission in the group taking quetiapine. At the 32-week mark, 22% of patients taking it were still in remission, as opposed to 14% of patients who had taken quetiapine plus antidepressants.
Researcher Andreas Reif of Goethe University Frankfurt, first author of the study, stated: “The ESCAPE-TRD trial was an open-label, single-blind, randomised, controlled trial, conducted across 171 sites comprising hospitals, inpatient and outpatient clinics, and research centres 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.
“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.”
“There were other differences we saw over time,” added researcher Professor Allan Young of Kings College London who collaborated with the study.
“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.
“In addition, esketamine NS‑treated patients were 1.5 times as likely to achieve the key secondary endpoint, remaining relapse free through Week 32. Indeed, by Week 32, approximately half of patients receiving esketamine NS were in remission, while two thirds were responders, emphasising the importance of continuing treatment in those who do not achieve remission in the acute phase.”
Commenting, Dr Josep Antoni Ramos-Quiroga from Vall Hebron University Hospital (CIBERSAM) and Autonomous University of Barcelona, who was not involved in the study, said: “The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine. This gives people with treatment-resistant depression more safe treatment options.”
