OBJECTIVE: Esketamine is an FDA-approved treatment for treatment-resistant depression (TRD) or major depression with acute suicidal ideation or behavior (MDSI). This analysis addressed the lack of data on real-world characteristics of patients with TRD and MDSI or prescribed esketamine. METHODS: Data were derived from the Adelphi Real World Depression Disease Specific Programme a cross-sectional survey of physicians and patients with TRD, MDSI, or those prescribed esketamine in the US (July 2022-February 2023). Physicians reported demographic and clinical characteristics, patients completed PHQ-9 and WPAI measures. RESULTS: Of 914 patients enrolled in the survey, 66.2% had TRD and 33.8% MDSI. Mean (± standard deviation) PHQ-9 scores were 8.3 ± 6.3 (TRD) and 9.3 ± 6.3 (MDSI), with moderate-to-very severe depression reported by 36.5% (TRD) and 48.3% (MDSI) of patients. Mean work impairment was 26.0 ± 28.1% and overall impairment 34.7 ± 27.3%. No-to-mild impairment was reported for most patients in ability to meet basic needs, social functioning, work, overall quality of life and general health. Patients and physicians showed low levels of agreement on disease severity and trajectory. Patients prescribed esketamine ( CONCLUSIONS: The substantial impact of TRD and MDSI on daily life and unmet treatment need was underestimated by physicians. Patients treated with esketamine reported favorable outcomes.