In people with treatment-resistant depression, esketamine nasal spray outperformed quetiapine extended release across multiple measures. Sensitivity analyses using different definitions of remission and relapse consistently favored esketamine, with relative risks for the primary endpoint ranging from 1.462 to 1.737 and for the key secondary endpoint from 1.417 to 1.838. Esketamine also shortened time to first remission by 71% and confirmed remission by 66%. The robustness of the original ESCAPE-TRD trial findings was confirmed.
About 10-30% of people with major depressive disorder have treatment-resistant depression (TRD), and most do not respond to real-world treatments. An indirect comparison of two studies found that after six months, patients with TRD who received esketamine nasal spray plus an antidepressant had a 25.6% probability of achieving functional remission, measured by a Sheehan Disability Scale score of 6 or less, compared to an adjusted 11.5% probability for those receiving real-world treatments. This represents a relative risk of 2.226. Across both groups, patients who did not achieve clinical response or remission had low probabilities of functional remission (5.84% and 8.76%, respectively), while those who did had higher probabilities (43.