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

Among 163 patients with treatment-resistant depression treated with esketamine nasal spray in real-world US settings, depressive symptoms improved significantly over six months. Average PHQ-9 scores dropped by 3.2 points within the first three months and by 4.4 points between three and six months after starting treatment. The proportion of patients with moderately severe or severe depression fell from 55.8% at baseline to 37.1% at three months and 25.0% at six months, while the share with minimal or mild depression increased. These findings suggest esketamine, approved in 2019 for treatment-resistant depression, is effective outside clinical trials.

Study at a glance

Abstract

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.