- Title
- 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
- Creator
- Loo, Colleen; Glozier, Nick; Alonzo, Angelo; Dong, Vanessa; Martin, Donel; Nikolin, Stevan; Mitchell, Philip B.; Berk, Michael; Carter, Gregory; Hackett, Maree; Leyden, John; Hood, Sean; Barton, David; Somogyi, Andrew A.; Lapidus, K; Stratton, E; Gainsford, K; Garg, D; Thornton, NLR; Fourrier, C; Richardson, K; Rozakis, D; Scaria, A; Baune, Bernhard T.; Mihalopoulos, C; Chatterton, ML; McDonald, WM; Boyce, P; Holtzheimer, PE; Kozel, FA; Riva-Posse, P; Rodgers, A; Mills, Natalie T.; Fitzgerald, Paul; Glue, Paul; Sarma, Shanthi; Galvez-Ortiz, Veronica; Hadzi-Pavlovic, Dusan
- Relation
- British Journal of Psychiatry Vol. 223, Issue 6, p. 533-541
- Publisher Link
- http://dx.doi.org/10.1192/bjp.2023.79
- Publisher
- Cambridge University Press
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- ketamine/esketamine; major depressive disorder; clinical drug studies; neuroscience; affective disorders
- Identifier
- http://hdl.handle.net/1959.13/1494355
- Identifier
- uon:53779
- Identifier
- ISSN:0007-1250
- Rights
- x
- Language
- eng
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