Ketamine shows rapid antidepressant effects in major depressive disorder, including treatment-resistant depression, but many patients do not respond, and predicting who will benefit is difficult. This study will examine computational mechanisms behind changes in the auditory mismatch negativity response after intravenous ketamine, linking them to neural causes using a hierarchical Bayesian model and a neural mass model. Thirty patients with treatment-resistant depression will undergo EEG recordings during an auditory mismatch negativity task before three of four ketamine infusions, with depression, suicidality, and anxiety assessed throughout. The findings may improve understanding of treatment response and resistance, and model parameters could enable single-patient treatment predictions.
A pilot trial will test whether weekly inhaled nitrous oxide is feasible and preliminarily effective for treatment-resistant depression compared with the active placebo midazolam. Forty participants will receive either nitrous oxide (1 hour at 50% concentration) plus intravenous saline or oxygen (1 hour at 50% concentration) plus intravenous midazolam once per week for 4 weeks, with 6 weeks of follow-up. Feasibility will be assessed by recruitment and withdrawal rates, adherence, missing data, and adverse events. The main exploratory clinical outcome is change in depression scores at day 42. Results will guide a future definitive trial.