In this week’s episode of PsyQ, we break down the American Journal of Psychiatry review “Ketamine for Depression, but at What Cost?” by Li and colleagues. Here we explore the balance between ketamine’s rapid antidepressant benefits and its potential neurotoxic risks. We’ll discuss what animal and human studies reveal about dose, frequency, and safety, why FDA-regulated esketamine appears cognitively safe while off-label ketamine use raises concern, and how clinicians can responsibly navigate this evolving treatment landscape.

Reference: Li SW, Kumpf KT, Urrutia J, Krystal JH, Sanacora G, Wilkinson ST. Ketamine for Depression, but at What Cost? A Review of Ketamine’s Neurotoxic Effects From Preclinical and Human Studies. Am J Psychiatry. 2025;182:903–912.

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