Inclusion Criteria:  DSM-5 diagnosis of Major Depressive Disorder (MDD) without psychotic features (296.22, 296.23, 296.32, 296.33) made through the Structured Clinical Interview for the DSM-V (SCID-V). MADRS score ≥ 25 Pharmacologically treatment-resistant depressive episode [Stage ≥ II, defined by Thase & Rush (1997): failure of at least 2 adequate trials of at least 2 distinctly different classes of antidepressants (≥ 4 weeks each)] (88). Age: 18 - 50 years Written informed consent  Exclusion Criteria:  Participation in another interventional clinical trial Relative contraindications to ECT treatment in accordance with the consensus paper of the Austrian Society of Psychiatry and Psychotherapy: Patients who meet any exclusion criteria for nasal esketamine treatment as described in the clinical guidelines Contraindications to the conduction of MRI  History of one or more of the following diagnoses (DSM-5):  MDD, single or recurrent episode with psychotic features (296.24; 296.34) past or current substance dependence (except caffeine, nicotine) (303.x, 304.x, 305.x) neurodevelopmental disorders (299.x, 307.x, 314.x, 315.x, 319.x) schizophrenia spectrum and other psychotic disorders (293.x, 295.x, 297.x, 298.x) neurocognitive disorders (290.x, 292.x, 294.x, 331.x). history of ECT (unsuccessful or successful) suicidal tendency requiring admission in a locked ward pregnancy or lactation period lack of anesthetic clearance for any other reason insufficient command of German language.