In treatment-resistant depression, esketamine nasal spray combined with an SSRI or SNRI led to remission in 27.1% of patients at week 8, compared to 17.6% for extended-release quetiapine plus an SSRI or SNRI. Over 32 weeks, 21.7% of patients on esketamine had no relapse after remission versus 14.1% on quetiapine. The open-label, single-blind, randomized trial included 676 patients. Adverse events matched known safety profiles. Esketamine was superior to quetiapine for achieving remission and preventing relapse.
In the ESCAPE-TRD trial, esketamine nasal spray caused treatment-emergent adverse events more often than quetiapine extended release (91.9% versus 78.0%), but these events were typically mild or moderate and transient: 92.0% resolved the same day, and only 4.2% of patients discontinued esketamine due to adverse events compared with 11.0% for quetiapine. The median proportion of days with adverse events was lower with esketamine (11.9% versus 21.3%). Along with greater efficacy, esketamine's tolerability profile supports its use for treatment-resistant depression.
Patients with treatment-resistant depression who received esketamine nasal spray experienced 43.2% more weeks with functional remission over 32 weeks compared to those taking quetiapine extended release, a difference of 2.0 weeks. Esketamine also led to an 11.9% reduction in productivity loss due to absenteeism and a 14.2% reduction in overall work productivity loss. Both treatments were taken alongside an ongoing SSRI or SNRI. The findings suggest that esketamine provides greater improvements in daily functioning and workplace productivity for this patient group.