Depression improves faster with electroconvulsive treatment (ECT) than with antidepressant medications. Ketamine, an N-methyl-D-aspartate-receptor antagonist, has rapid antidepressant effects when given intravenously. In a randomized trial of 60 hospitalized patients aged 18–45 with major depressive disorder, those receiving ketamine as anesthesia during modified ECT required significantly fewer sessions to achieve remission and showed faster improvement on depression rating scales compared to those receiving thiopentone anesthesia. The ketamine group also needed lower stimulus intensity and had longer seizure duration. Ketamine anesthesia appears to be a better option when rapid response to ECT is desired.
Depression treatments that target monoamine neurotransmitters often fail to achieve full remission. This narrative review examines several emerging strategies that go beyond those conventional methods: glutamatergic modulation, brain stimulation techniques, anti-inflammatory agents, interventions on the gut-brain axis, GABA modulation, and psychedelic-assisted therapy. The article describes the mechanisms, clinical efficacy, and safety profiles of these innovative approaches, offering perspectives for improving depression management and addressing current therapeutic gaps.