The honest answer is that we don't know. Experimentally, it works. There are theories (google will give you a couple vaguely plausible mechanisms), but it's to

The honest answer is that we don't know. Experimentally, it works. There are theories (google will give you a couple vaguely plausible mechanisms), but it's too early to say. And it's likely that the antidepressive effect of ketamine has nothing to do with its NMDA antagonism, given that other NMDA receptor antagonists do not work as antidepressives. Neuroscience theory lags far behind applied psychiatry, so all know is people whose depression resists normal treatment now have another very promising option, with a very different mechanism from normal antidepression treatment.