Comparison of Real-world Response and Remission among Patients with Treatment-Resistant Depression Treated with Esketamine Nasal Spray or Antipsychotic Augmentation

BACKGROUND: Esketamine nasal spray and second-generation antipsychotic augmentation (SGA) are approved therapies for treatment-resistant depression (TRD). Prospective randomized ESCAPE-TRD clinical trial demonstrated significantly greater likelihood of response and remission with esketamine versus SGA; however, real-world evidence regarding their relative effectiveness remains limited.
METHODS: Patients with TRD initiated on esketamine or SGA (index date) with ≥12 months of activity pre-index date (baseline) and ≥6 months post-index were identified using Komodo Research Database open claims (01/2016-06/2023). Esketamine patients were matched 1:1 to SGA patients based on exact matching (baseline PHQ-9 scores) and propensity scores (baseline demographic and clinical characteristics). Time to response (≥50% decrease in PHQ-9 score from baseline) and remission (PHQ-9 score < 5) were evaluated while on treatment and were described using Kaplan-Meier survival analysis and compared between matched cohorts with Cox proportional hazard models.
RESULTS: Each cohort included 254 patients after matching. In esketamine and SGA cohorts, respectively, mean baseline PHQ-9 score was 14.9 and 14.6, mean age was 44.2 and 44.3 years, 63.4% and 61.0% were female. At 12 months post-index, 49.6% versus 41.7% achieved response and 37.7% versus 28.3% achieved remission among esketamine and SGA cohorts, respectively. Esketamine was associated with significantly higher chances of response (hazard ratio [HR]: 1.45, p=0.012) and remission (HR: 1.49, p=0.041) compared to SGA at 12 months post-index.
CONCLUSION: Patients with TRD treated with esketamine were significantly more likely to reach response and remission relative to SGA, aligning with the ESCAPE-TRD clinical trial evidence that demonstrated higher efficacy of esketamine over SGA.