Electroconvulsive therapy (ECT) deliberately induces generalized seizures to treat severe psychiatric illness, offering a chance to study how consciousness, cognition, and brain activity recover after seizures. Fifteen patients with treatment-resistant major depressive disorder will receive right unilateral ECT under etomidate anesthesia. They will then undergo three treatments in randomized order: etomidate plus ECT, ketamine plus ECT, and ketamine plus sham ECT, repeated for six total sessions. Cognitive tests assess sensorimotor speed, working memory, and executive function before and after each treatment. The study will measure time to return of responsiveness, cognitive recovery trajectories, postictal delirium, and EEG changes. It aims to develop biomarkers for tailoring cognitive and emotional recovery in ECT patients.
A single 1-hour inhalation of 25% nitrous oxide improves depressive symptoms in patients with severe treatment-resistant major depression as effectively as 50% nitrous oxide, but with substantially fewer adverse effects. In a phase 2 crossover trial with 24 patients, both concentrations significantly reduced depression scores on the Hamilton Depression Rating Scale compared to placebo over two weeks. The 25% dose showed significant improvements at week 1 and week 2, while the 50% dose showed significant improvement at week 2. Adverse events declined substantially with the lower dose.
NMDAR antagonists like ketamine and nitrous oxide are being studied as rapid-acting antidepressants. Intravenous ketamine rapidly reduces depressive and suicidal symptoms in treatment-resistant depression (TRD), as shown by several trials. The FDA has approved intranasal esketamine for TRD, with a REMS program to minimize misuse. Nitrous oxide, a gas used for anesthesia and analgesia, also acts as an NMDAR inhibitor. A recent double-blind, prospective, cross-over study found that nitrous oxide reduced depressive symptoms in severely ill TRD patients, though further research is needed.