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Loo, C K, Glozier, N, Barton, D, Baune, B T, Mills, N, Fitzgerald, P B, Glue, P, Sarma, S, Galvez-Ortiz, V, Hadzi-Pavlovic, D, Alonzo, A, Dong, V, Martin, D M, Nikolin, S, Mitchell, P B, Berk, M, Carter, G, Hackett, M, Leyden, J, Hood, S, Somogyi, A, Lapidus, K, Stratton, E, Gainsford, K, Garg, D, Thornton, N, Fourrier, C, Richardson, K, Rozakis, D, Scaria, A, Mihalopoulos, C, Chatterton, M L, McDonald, W, Boyce, P, Holtzheimer, P, Kozel, F A, Riva-Posse, P & Rodgers, A 2023, 'Efficacy and Safety of Repeated Subcutaneous Ketamine Injections for Treatment Resistant Depression - The .... |
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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. |