Real-world evaluation of change in depressive symptoms among patients with treatment-resistant depression treated with esketamine

Abstract Background Treatment-resistant depression (TRD) is often characterized by inadequate response to ≥ 2 oral antidepressant treatments of adequate dose and duration during a major depressive episode (MDE). Esketamine nasal spray (ESK) was approved by the US Food and Drug Administration in 2019 for TRD in conjunction with an oral antidepressant under a Risk Evaluation and Mitigation Strategy ( https://www.spravatorems.com/ ). While there are extensive clinical trial data demonstrating the efficacy and safety of esketamine use in TRD, the real-world data are limited. This study evaluated the change in depressive symptoms following esketamine initiation among patients with TRD in real-world settings.

Methods: Patients with TRD treated with esketamine between 2019 and 2022 were identified from the PremiOM™ Major Depressive Disorder (MDD) Dataset, which includes > 440,000 patients in the US with linked claims and electronic medical record (EMR) data. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Baseline scores were within 6 months prior to the first esketamine prescription (“index date”) and were compared to the most recent scores at > 0-3-months and > 3–6 months after index.

Results: 163 patients were included (mean age 49.5 years, 58.3% female). Among patients with baseline and follow-up scores, statistically significant reductions in mean PHQ-9 scores were observed at > 0–3 months of -3.2 points, (95% CI: -4.5, -2.0; p < 0.001); and > 3–6 months of -4.4 points (95% CI: -5.7, -3.2; p < 0.001). The percentage of patients with moderately severe or severe depression at baseline was 55.8%. This decreased to 37.1% at > 0–3 months and 25.0% at > 3–6 months. Concomitantly, the percentages of patient with minimal depression and patients with mild to minimal depression increased.

Conclusions: Among patients with TRD treated with esketamine in real-world settings, significant improvements in depressive symptoms were observed over the six months following treatment initiation.