Novel rapid-acting antidepressants: molecular and cellular signaling mechanisms

Depression is a chronic, debilitating, and common illness. Currently available pharmacotherapies can be helpful but have several major drawbacks, including substantial rates of low or no response and a long therapeutic time lag. In pursuit of better treatment options, recent research has focussed on rapid-acting antidepressants, including the N-methyl-d-aspartate (NMDA) receptor (NMDAR) antagonist ketamine, which affects a range of signaling pathways in ways that are distinct from the mechanisms of typical antidepressants. Because ketamine and similar drugs hold the promise of dramatically improving treatment options for depressed patients, there has been considerable interest in developing new ways to understand how these compounds affect the brain. Here, we review the current understanding of how rapid-acting antidepressants function, including their effects on neuronal signaling pathways and neural circuits, and the research techniques being used to address these questions.