In this episode, we tackle the complex challenge of co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). Traditional treatments often fall short, leaving many seeking new hope. This episode unpacks a groundbreaking study by Yoon, Crystal, and colleagues from VA Connecticut and Yale. They explored ketamine's efficacy in a rigorous, three-arm, double-blind trial with 65 adults struggling with both MDD and AUD. While initial depression relief was seen across all groups, ketamine's antidepressant effects proved significantly more durable. Surprisingly, naltrexone, an opioid blocker, didn't diminish ketamine's mood benefits, challenging existing theories about its mechanism. This points to other pathways, like the glutamate system, as crucial. Though ketamine didn't directly reduce alcohol use or craving more than the control , it showed remarkable improvements in anxiety and overall quality of life. Fascinatingly, adding naltrexone to ketamine led to even greater anxiety reduction, suggesting a targeted benefit for this combination. Join us as we reveal these nuanced findings, offering considerable hope for those battling both MDD and AUD. Discover how ketamine's lasting impact on mood, anxiety, and well-being could reshape personalized treatment approaches. Reference: Yoon, G., Pittman, B., Ralevski, E., Petrakis, I. L., & Krystal, J. H. (2025). Antidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: A randomized controlled trial. International Journal of Neuropsychopharmacology. https://doi.org/10.1093/ijnp/pyaf056