Core Viewpoint - The article discusses a significant breakthrough in understanding the treatment mechanisms of resistant depression, revealing a common neurobiological mechanism behind ketamine and electroconvulsive therapy (ECT) that could lead to safer and more effective treatments [3][5]. Group 1: Research Findings - A recent study published in Nature identified that both ketamine and ECT treatments for resistant depression significantly increase adenosine levels in key brain areas [4][5]. - The research indicates that adenosine signaling is the core pathway driving the rapid antidepressant effects of both therapies, challenging the traditional focus on NMDA receptor inhibition [5][6]. - Approximately one-third of depression patients are classified as having resistant depression, which does not respond well to conventional treatments [5][6]. Group 2: Implications for Treatment - The study's findings suggest that understanding the adenosine pathway could help decouple the efficacy of treatments from their side effects, which include potential addiction and cognitive impairments [5][6]. - The research team has developed a new ketamine derivative that shows superior antidepressant effects at lower doses with reduced side effects, indicating strong clinical translation potential [7]. - A novel non-drug therapy called acute intermittent hypoxia (aIH) has been identified, which effectively activates the brain's adenosine signaling and demonstrates promising antidepressant effects [8]. Group 3: Future Directions - The research team is collaborating with clinical teams to advance clinical trials for the aIH therapy, aiming to explore its potential as a core component of combined treatment strategies [8]. - The ongoing development of drug screening platforms based on the adenosine pathway is expected to deepen the understanding and application of new therapeutic options for resistant depression [8].