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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.

Cardiac magnetic resonance (CMR) imaging could enable major advantages when guiding in real-time cardiac electrophysiology procedures offering high-resolution anatomy, arrhythmia substrate, and ablation lesion visualization in the absence of ionizing radiation. Over the last decade, technologies and platforms for performing electrophysiology procedures in a CMR environment have been developed. However, performing procedures outside the conventional fluoroscopic laboratory posed technical, practical and safety concerns. The development of magnetic resonance imaging compatible ablation systems, the recording of high-quality electrograms despite significant electromagnetic interference and reliable methods for catheter visualization and lesion assessment are the main limiting factors. The first human reports, in order to establish a procedural workflow, have rationally focused on the relatively simple typical atrial flutter ablation and have shown that CMR-guided cavotricuspid isthmus ablation represents a valid alternative to conventional ablation. Potential expansion to other more complex arrhythmias, especially ventricular tachycardia and atrial fibrillation, would be of essential impact, taking into consideration the widespread use of substrate-based strategies. Importantly, all limitations need to be solved before application of CMR-guided ablation in a broad clinical setting., Competing Interests: Conflict-of-interest statement: All the authors have no conflicts to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)