Objective: ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch. Methods: Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient's care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program 'Temporary Authorisation for Use' (ATU), post-ATU, and post-launch cohorts. Results: The overall ESKALE cohort (N = 160 included; n = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts. Conclusion: These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.