Adding a low dose of the drug ketamine to the anesthetic used during electroconvulsive therapy (ECT) does not improve memory or speed recovery in severely depressed patients. In a randomized trial of 79 patients, those who received ketamine scored no better on a test of delayed verbal recall after four ECT sessions than those who received a placebo (saline). The ketamine group actually scored slightly lower on average, and the results rule out any more than a small to moderate benefit. Patients receiving ketamine also reported more adverse events, including transient psychological effects. The findings do not support using ketamine as a routine addition to ECT.
Ketamine, which blocks N-methyl-D-aspartate receptors (NMDARs), robustly alters functional connectivity in the human brain, shifting patterns from cortex-centered to subcortex-centered connections. This effect was detected with 87.5% accuracy compared to saline. Pre-treatment with risperidone strongly modulated the connectivity changes (81.25% accuracy), whereas lamotrigine did not (43.75% accuracy). The differential modulation suggests the connectivity effects stem primarily from NMDAR blockade rather than downstream glutamate release. No such differential effect was seen in measures of brain response amplitude, underscoring the value of connectivity analysis for understanding how drugs affect the brain.