Montgomery-Åsberg Depression Rating Scale Anhedonia Factor Score Following Esketamine Nasal Spray Monotherapy in Adult Patients With Treatment-Resistant Depression: A Post Hoc Analysis

Objective: This post hoc analysis of a phase 4, double-blind, multicenter study (NCT04599855) evaluated changes in anhedonia symptoms through 4 weeks of esketamine nasal spray (ESK) monotherapy compared with placebo in patients with treatment-resistant depression.

Methods: Patients were randomly assigned to receive ESK 56 mg, ESK 84 mg, or placebo twice weekly for 4 weeks. The 5-item Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor score (composite of items apparent sadness, reported sadness, concentration difficulties, lassitude, inability to feel) was evaluated through day 28. Response rates (≥50% improvement in score) are summarized. Treatment-emergent adverse events (TEAEs) were monitored throughout.

Results: This analysis included 378 patients (ESK 56 mg, n=86; ESK 84 mg, n=95; placebo, n=197). Mean MADRS anhedonia factor score at baseline was 21.5 across groups. MADRS anhedonia factor score significantly improved in patients treated with ESK compared with placebo at day 28 (mean change from baseline, ESK 56 mg, −7.1; ESK 84 mg, −8.5; placebo, −3.7; P< 0.001) and as early as 24 hours after treatment (mean change from baseline, ESK 56 mg, −7.8; ESK 84 mg, −7.9; placebo, −5.1; P< 0.01). On day 28, response rates for ESK 56 mg and 84 mg were 31.7% and 33.7%, respectively, and for placebo, 16.2%. Most common TEAEs included nausea, dissociation, dizziness, and headache, consistent with the established safety profile for ESK.

Conclusion: ESK monotherapy significantly improved anhedonia symptoms measured by the 5-item MADRS anhedonia factor score at day 28 and as early as 24 hours post treatment. No new safety signals were identified.