There is increased evidence for the mediation of glutamate in the pathophysiology of depression, as suggested by the potential antidepressant effect of drugs that modulate glutamate transmission. Open studies and recent case reports demonstrate a rapid antidepressant effect of intravenous ketamine - a non-competitive antagonist at the glutamate N-methyl-D-aspartate (NMDA) receptor. Ketamine is a general anesthetic used commonly for procedural sedation. Ketamine has no anticonvulsant properties. It is used as an alternative to methohexital - a barbiturate with anticonvulsant properties - in patients with high seizure threshold. A recent open non-randomized trial by Okamoto shows a faster response when ECT is given with ketamine anesthesia. In a recent review Gregory-Roberts et al suggest that available evidence in animals and humans supports the prediction that ketamine could effectively prevent ECT -induced persistent retrograde amnesia and improve or hasten therapeutic response.