We found that these changes in molecular neuroplasticity revolving glutamate, AMPA receptors (AMPAR), mTOR, BDNF/TrkB, VGF, eEF2K, p70S6K, GSK-3, IGF2, Erk, and microRNAs may likely be responsible in mediating and producing ketamine’s rapid antidepressant effects in MDD and bipolar disorder depression. This evidence concerns the gene RPS6KB1 and major depressive disorder.