Will We Have Rapid-Onset Antidepressants? How Might They Work?

Virtually all classes of current antidepressant medications must be taken for a frustratingly long time, usually several weeks, before the drugs even begin to offer symptom relief. This delay has been attributed to an “initiation and adaptation” paradigm, in which antidepressants are thought to simply initiate a complex cascade of events that ultimately lead to adaptations in neurotrophic signaling and in the glutamatergic system.

Recently, encouraging glimmers have appeared regarding potential faster-onset antidepressants that act more directly on these downstream processes, and researchers have started to elucidate the drugs' potential mechanisms of action. The N-methyl-d-aspartate (NMDA) receptor (particularly its NR2 subunit, the major g…