Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

Autor:	Loo C; Black Dog Institute, University of New South Wales, Randwick, New South Wales, Australia; and George Institute for Global Health, Newtown, New South Wales, Australia., Glozier N; Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; and Australian Research Council Centre of Excellence for Children and Families over the Life Course, University of Sydney, Sydney, New South Wales, Australia., Barton D; Australian Centre for Heart Health, Royal Melbourne Hospital, North Melbourne, Victoria, Australia; and NeuroCentrix, South Carlton, Victoria, Australia., Baune BT; Department of Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia; and Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia., Mills NT; Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia., Fitzgerald P; Australian National University School of Medicine and Psychology, Canberra, Australian Capital Territory, Australia., Glue P; Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Sarma S; Mental Health and Specialist Services, Gold Coast Health, Bond University, Robina, Queensland, Australia., Galvez-Ortiz V; Department of Psychiatry and Mental Health, Hospital Universitari Parc Tauli, Sabadell, Spain; and Institut Investigacio I Innovacio Parc Tauli, Sabadell, Spain., Hadzi-Pavlovic D; Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia., Alonzo A; Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia; University of New South Wales, Randwick, New South Wales, Australia; and George Institute for Global Health, Newtown, New South Wales, Australia., Dong V; Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia; University of New South Wales, Randwick, New South Wales, Australia; and George Institute for Global Health, Newtown, New South Wales, Australia., Martin D; Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia; University of New South Wales, Randwick, New South Wales, Australia; and George Institute for Global Health, Newtown, New South Wales, Australia., Nikolin S; Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia; University of New South Wales, Randwick, New South Wales, Australia; and George Institute for Global Health, Newtown, New South Wales, Australia., Mitchell PB; Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia., Berk M; Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Barwon Health, Deakin University, Geelong, Australia., Carter G; College of Health, Medicine and Wellbeing, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia., Hackett M; George Institute for Global Health, Newtown, New South Wales, Australia., Leyden J; Royal North Shore Hospital, St Leonards, New South Wales, Australia; and Northern Sydney Anaesthetic Research Institute, St Leonards, New South Wales, Australia., Hood S; Division of Psychiatry, University of Western Australia, Perth, Western Australia, Australia., Somogyi AA; Discipline of Pharmacology, School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia., Lapidus K; Affective Care, Northwell Health, New York, New York, USA., Stratton E; Faculty of Medicine and Health, Central Clinical School, University of Sydney, Sydney, New South Wales, Australia., Gainsford K; Epworth Centre for Innovation in Mental Health, Epworth Healthcare and Monash University, Camberwell, Victoria, Australia., Garg D; Mental Health and Specialist Services, Gold Coast Health, Bond University, Robina, Queensland, Australia., Thornton NLR; Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; and Australian Research Council Centre of Excellence for Children and Families over the Life Course, University of Sydney, Sydney, New South Wales, Australia., Fourrier C; Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia; and Lysosomal Health in Ageing, Hopwood Centre for Neurobiology, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., Richardson K; BrainPark, Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia; and Epworth Centre for Innovation in Mental Health, Epworth Healthcare and Monash University, Camberwell, Victoria, Australia., Rozakis D; NeuroCentrix, Noble Park, Victoria, Australia., Scaria A; George Institute for Global Health, Newtown, New South Wales, Australia., Mihalopoulos C; School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; and School of Health and Social Development, Deakin University, Geelong, Australia., Chatterton ML; School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia., McDonald WM; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA., Boyce P; Specialty of Psychiatry, Westmead Institute of Medical Research, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia., Holtzheimer PE; Department of Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA; and Department of Surgery, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA., Kozel FA; Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, Florida, USA., Riva-Posse P; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA., Rodgers A; George Institute for Global Health, Newtown, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	The British journal of psychiatry : the journal of mental science [Br J Psychiatry] 2023 Dec; Vol. 223 (6), pp. 533-541.
DOI:	10.1192/bjp.2023.79
Abstrakt:	Background: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. Aims: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. Method: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. Results: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v . 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v . 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. Conclusions: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Databáze:	MEDLINE
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