Given that ketamine and other NMDA receptor antagonists produce an activity-dependent release of brain-derived neurotrophic factor (BDNF), which acts as a pivotal mediator of synaptic plasticity [117], our findings illustrate a shift from the traditional monoamine hypothesis to a neuroplasticity hypothesis of depression, reflected in the landscape of pharmacotherapy for depression over the past fifteen years. This evidence concerns the gene BDNF and major depressive disorder.