(#12) Change in Clinician-Rated and Patient-Reported Depression Severity After Esketamine Nasal Spray as Monotherapy in Adult Patients With Treatment-Resistant Depression: A Post Hoc Analysis of Item Scores

Abstract: Objective: To evaluate improvements in items of the Montgomery-≈sberg Depression Rating Scale (MADRS) and Patient Health Questionnaire-9 (PHQ-9) over 4 weeks of esketamine nasal spray (ESK) monotherapy. Methods: In this double-blind multicenter study (NCT04599855), patients were randomly assigned on day 1 to ESK 56 mg, ESK 84 mg, or placebo (PBO) twice weekly for 4 weeks. Mean change from baseline in MADRS and PHQ-9 items between treatment groups were evaluated using analysis of covariance models at day 2 (D2; MADRS), D15, and D28 (MADRS and PHQ-9). Treatment-emergent adverse events (TEAEs) were monitored throughout. Results: The analysis included 378 patients (PBO, n=197; ESK 56 mg, n=86; ESK 84 mg, n=95), with baseline MADRS and PHQ-9 total scores of 37.3 and 20.0, respectively. All MADRS and PHQ-9 items improved from baseline to D28 with ESK. MADRS ratings of reported sadness and apparent sadness were significantly decreased in both ESK groups on D2 and D28; inner tension, reduced appetite, concentration difficulties, lassitude, and inability to feel were significantly decreased on D28 (all P 0.05 vs PBO). PHQ-9 items of little interest/pleasure and feeling down/depressed/hopeless were significantly decreased in both ESK groups on D15 and D28; trouble falling/staying asleep, feeling tired/little energy, feeling bad about yourself, trouble concentrating, and moving slowly/fidgety/restless were significantly decreased on D28 (all P 0.05 vs PBO). Common TEAEs included nausea, dissociation, dizziness, and headache. Conclusion: ESK monotherapy improved depression severity as early as D2 in all items of MADRS and PHQ-9; improvements continued through D28. No new safety signals were identified.Short Description: This post hoc analysis of a randomized controlled study (NCT04599855) evaluated change from baseline in individual items of Montgomery-≈sberg Depression Rating Scale and Patient Health Questionnaire-9 items in adults (n=378) with treatment-resistant depression following 4 weeks of esketamine nasal spray (ESK) monotherapy. Results show severity of core depressive symptoms significantly improved as early as 24 hours post first dose of ESK monotherapy and continued through day 28. No new safety signals were identified.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC, a Johnson & Johnson company