Real-world clinical effectiveness of esketamine nasal spray based on the Montgomery-Asberg Depression Rating Scale (MADRS) among patients with treatment-resistant depression in the United States

BACKGROUND: Clinical trials for esketamine nasal spray in treatment resistant depression (TRD) often assess efficacy using Montgomery-Asberg Depression Rating Scale (MADRS)-based primary endpoints. To benchmark esketamine's real-world effectiveness against trials, this study analyzed MADRS data from a multi-site psychiatric practice in the United States.
METHODS: Adults with TRD initiated on esketamine (first session=index date) were identified at Mindful Health Solutions clinics during 03/2019-01/2024. Baseline MADRS score was the most recent score before or on the index date. Mean change in MADRS score from baseline, reported at 4-week increments during the follow-up period (index date till end of patient clinical activity or data), was estimated with generalized estimating equations. Among patients with baseline MADRS score ≥28 (moderate-to-severe depression), time to response (≥50% decrease from baseline) and remission (score ≤12) was described using Kaplan-Meier survival analysis.
RESULTS: Among 853 patients identified (mean baseline MADRS score: 34.9), 727 (85.2%) had baseline MADRS score ≥28. During the mean follow-up of 12.9 months, patients completed 26.2 esketamine sessions on average. Mean change in MADRS score from baseline was -6.8, -12.9, -15.5, and -17.7, at 4, 8, 28, and 52 weeks after esketamine initiation, respectively (all p < 0.001). At 12 months, the probability of achieving response was 79.4% and remission was 52.7%.
CONCLUSIONS: Within a year of esketamine initiation, patients achieved clinically meaningful reduction in depressive symptoms (≥10 points), most achieved treatment response, and over half achieved remission. Results from this study are consistent with esketamine clinical trials supporting the real-world effectiveness of esketamine.