(#19) Efficacy and Safety of Esketamine Nasal Spray as Monotherapy in Adult Patients with Treatment-Resistant Depression for up to 4-Months of Treatment: A Post Hoc Analysis

Abstract: Objective: To evaluate the efficacy and safety of esketamine nasal spray (ESK) monotherapy in adults with treatment-resistant depression (TRD) from a multicenter study (NCT04599855). Methods: During double-blind (DB) treatment, patients were randomly assigned to ESK 56mg, ESK 84mg, or placebo (PBO), twice weekly for 4 weeks. Open-label (OL) ESK treatment (12 weeks) consisted of flexible ESK dosing (56 or 84mg) and an oral antidepressant (OAD) if indicated. Assessments were based on Montgomery-≈sberg Depression Rating Scale (MADRS) total scores (change over time, clinically substantial improvement [12-point reduction], response [?50% reduction], and remission [total score ?12]) at DB and OL end points. Treatment-emergent adverse events (TEAEs) were monitored throughout. Results: The analysis included 227 ESK monotherapy patients without add-on OADs (PBO, 121; ESK 56mg, 48; ESK 84mg, 58). At DB end point, mean (SD) changes in MADRS total score from baseline were ?7.9 (10.9), ?15.3 (12.7), and ?16.7 (12.3) for PBO, ESK 56mg, and ESK 84mg, respectively. From DB end point to OL end point, mean (SD) changes were ?12.2 (12.9), ?22.0 (13.4) and ?20.5 (12.4) for PBO/ESK, ESK 56mg/ESK and ESK 84mg/ESK groups, respectively. At OL end point, clinically substantial improvement was attained in 68.9%, 70.8%, and 77.6%; response in 58.0%, 60.4%, and 65.5%; and remission in 41.2%, 47.9%, 39.7% of patients, respectively. Common TEAEs included nausea, dissociation, dizziness, and headache. Conclusion: ESK monotherapy treatment for up to 4 months in adults with TRD was associated with clinically substantial and sustained improvements in depressive symptoms. No new safety signals were identified.Short Description: This post hoc analysis examined adults (n=227) with treatment-resistant depression who received esketamine nasal spray (ESK) monotherapy without add-on oral antidepressants in a multicenter study (NCT04599855). Assessments were based on changes in Montgomery-≈sberg Depression Rating Scale total scores after double-blind (4-week, fixed dose) and open-label (12-week, flexible dose) ESK treatment. ESK monotherapy treatment for up to 4 months was associated with clinically substantial and sustained improvements in depressive symptoms. No new safety signals were identified.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC, a Johnson & Johnson company