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

BackgroundPrior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.AimsTo assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD....

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Detalles Bibliográficos
Autores: Loo, C, Glozier, N, Barton, D, Baune, BT, Mills, NT, Fitzgerald, P, Glue, P, Sarma, S, Galvez-Ortiz, V, Hadzi-Pavlovic, D, Alonzo, A, Dong, V, Martin, D, Nikolin, S, Mitchell, PB, Berk, M, Carter, G, Hackett, M, Leyden, J, Hood, S, Somogyi, AA, Lapidus, K, Stratton, E, Gainsford, K, Garg, D, Thornton, NLR, Fourrier, C, Richardson, K, Rozakis, D, Scaria, A, Mihalopoulos, C, Chatterton, ML, Mcdonald, WM, Boyce, P, Holtzheimer, PE, Kozel, FA, Riva-Posse, P, Rodgers, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p4203
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/4203
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85166637623&doi=10.1192%2fbjp.2023.79&partnerID=40&md5=b682a7c65ba614fac3d7a8f996f918c7
Access Level:acceso abierto
Palabra clave:Ketamine/esketamine
major depressive disorder
clinical drug studies
neuroscience
affective disorders.
Descripción
Sumario:BackgroundPrior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.AimsTo 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.MethodThis 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-angstrom sberg Rating Scale for Depression score <= 10) at the end of week 4.ResultsThe 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.ConclusionsAdequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

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