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Esketamine Nasal Spray Combination Therapy Outperforms Quetiapine in TRD Treatment
The combination of esketamine nasal spray plus a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) has emerged as a superior treatment option for treatment-resistant depression (TRD), a type of major depressive disorder, compared to extended-release quetiapine plus an SSRI or SNRI. Researchers published the study results of the open-label, single-blind, multicenter, phase 3b, randomized, active-controlled trial in The New England Journal of Medicine.
“Although remission is the primary goal of initial treatment of depression, remission occurs in a markedly low percentage of patients who have required 3 or more consecutive treatments,” authors said in the study. “Thus, an unmet need exists for effective treatment options specifically for [TRD].”
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Patients with depression were given either flexible doses of esketamine nasal spray or extended-release quetiapine, along with an SSRI or SNRI, according to the summary of product characteristics. The primary endpoint was to achieve remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), by week 8. The MADRS scale ranges from 0 to 60, where higher scores indicate more severe depression. The key secondary endpoint was to prevent relapse through week 32 after achieving remission at week 8. All patients, including those who stopped treatment, were analyzed, and the primary and key secondary endpoints were compared, adjusting for age and the number of treatment failures.
Of the 336 patients in the ketamine group, 91 (27.1%) had remission at week 8 compared to 60 of the 340 patients (17.6%) in the quetiapine group. At week 32 after remission at week 8, 7 of the 336 patients (21.7%) in the ketamine group had no relapse compared to 48 of 340 patients (14.1%). In short, the percentage of patients with remission and treatment response and a change in the MADRS score from baseline favored esketamine nasal spray as a treatment option. The established safety profiles of the trial treatments were also consistent with adverse events.
“Extended-release quetiapine was chosen as an active comparator because it is approved for and frequently used as an augmentation treatment in patients with previous failed treatments,” researchers said of the study's limitations in clinical practice. “However, because real-world treatment is heterogeneous and lacks consensus, with patients receiving multiple antidepressant treatments during a major depressive episode, the generalizability of our findings is limited.”
With this study, researchers set out to discover data that could impact the existing guidelines for treatment with TRD—guidelines they said “lack uniformity.”
“Collectively, these data provide support for the use of esketamine nasal spray in [TRD] and may be of value for informing future guidelines,” authors concluded.
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