Electroconvulsive therapy combined with esketamine improved depression through PI3K/AKT/GLT-1 pathway.
Journal of affective disorders January 1, 2025 Xiangyang Zang, Jingting Zhang, Jingping Hu et al. 16 citations
Combining esketamine with electroconvulsive therapy (ECT) improves depression symptoms more than ECT alone. In a small human trial, patients receiving propofol plus esketamine before ECT had lower depression scores on the 24-item Hamilton Depression Rating Scale after the fifth and sixth treatments than those receiving propofol alone. In a rat model of depression, the combination reduced depression-like behaviors and lowered brain glutamate levels. Both esketamine and ECT activated the PI3K/Akt/GLT-1 pathway, which helps clear excess glutamate. Blocking this pathway with inhibitors eliminated the antidepressant effects, suggesting that activation of PI3K/Akt/GLT-1 is a key mechanism.