Participants will be randomised to receive either Spravato® or racemic ketamine treatment and asked to complete some questionnaires to assess the effects on mood, treatment acceptability, side effects, quality of life and function, and health economic outcomes. conditions: Treatment Resistant Depression studyType: INTERVENTIONAL phases: PHASE4 allocation: RANDOMIZED interventionModel: PARALLEL interventionModelDescription: Randomized, prospective, parallel group, comparative effectiveness trial. primaryPurpose: TREATMENT masking: SINGLE maskingDescription: Primary outcome raters will be blinded to treatment allocation. whoMasked: OUTCOMES_ASSESSOR count: 162 type: ESTIMATED name: Esketamine group name: Racemic ketamine measure: Montgomery-Asberg Depression Rating Scale (MADRS) measure: Montgomery-Asberg Depression Rating Scale (MADRS) score measure: Response - Montgomery-Asberg Depression Rating Scale (MADRS) measure: Remission - Montgomery-Asberg Depression Rating Scale (MADRS) measure: DASS-21 measure: Clinical Global Impression-Improvement (CGI-I) measure: Clinical Global Impression-Severity (CGI-S) measure: Columbia Suicide Severity Rating Scale (C-SSRS) measure: Speed of response - Clinical Global Impression-Improvement (CGI-I) measure: Psychotomimetic symptoms measure: Suicide attempts or gestures measure: Number of Participants with urinary symptoms, as assessed using the Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) measure: Cognitive Failure Questionnaire scores (CFQ) measure: Ketamine liking/craving score measure: Number of Participants with urinary symptoms, as assessed using the Ketamine Side Effect Tool (KSET) measure: Acceptability Questionnaire measure: All-cause dropouts measure: Recovering Quality of Life Questionnaire (REQOL-10) measure: WHO Disability Assessment Scale (WHODAS-12) measure: Patient Health Questionnaire-9 (PHQ-9) measure: Assessment of Quality of Life Questionnaire (AQoL-8D) measure: Resource Use Questionnaire (RUQ) sex: ALL minimumAge: 18 Years stdAges: ADULT stdAges: OLDER_ADULT facility: Royal Prince Alfred Hospital city: Camperdown state: New South Wales zip: 2050 country: Australia name: Hadley Lindsay role: CONTACT email: SLHD-RPA-KetamineClinic@health.nsw.gov.au name: Nicholas Glozier role: PRINCIPAL_INVESTIGATOR lat: -33.88965 lon: 151.17642 facility: Black Dog Institute city: Randwick state: New South Wales zip: 2031 country: Australia name: Stella Antoniou role: CONTACT email: depressionclinic@blackdog.org.au name: Adam Bayes role: PRINCIPAL_INVESTIGATOR lat: -33.91439 lon: 151.24895 facility: Ramsay Clinic Northside city: St Leonards state: New South Wales zip: 2065 country: Australia name: Mayra Ouriques role: CONTACT email: neuroinfo.nsc@ramsayhealth.com.au name: Colleen Loo role: PRINCIPAL_INVESTIGATOR lat: -33.82344 lon: 151.19836 facility: Ramsay Clinic Lakeside city: Warners Bay state: New South Wales zip: 2282 country: Australia name: Sally Sally Wilkinson role: CONTACT email: ClinicalTrialsUnit.WBP@ramsayhealth.com.au name: Natasha Cairns role: CONTACT email: ClinicalTrialsUnit.WBP@ramsayhealth.com.au name: Michael Bull role: PRINCIPAL_INVESTIGATOR lat: -32.97251 lon: 151.65268 facility: Gold Coast University Hospital city: Southport state: Queensland zip: 4215 country: Australia name: Catherine Donald role: CONTACT email: specialistmooddisorderclinic@health.qld.gov.au name: Shanthi Sarma role: PRINCIPAL_INVESTIGATOR lat: -27.96724 lon: 153.39796 facility: Ramsay Clinic Albert Road city: Melbourne state: Victoria zip: 3004 country: Australia name: Melanie Hurley role: CONTACT email: research.arc@ramsayhealth.com.au name: Malcolm Hopwood role: PRINCIPAL_INVESTIGATOR lat: -37.814 lon: 144.96332 hasResults: False