Antidepressants in the post-ketamine Era: Pharmacological approaches targeting the glutamatergic system.
Neuropharmacology February 1, 2023 Shigeyuki Chaki, Mai Watanabe
The limited efficacy of current antidepressants has driven research into the glutamatergic system as a drug target for depression, validated by ketamine's antidepressant effects and leading to the approval of esketamine (Spravato®). However, ketamine and esketamine have adverse effects that limit routine use. Understanding ketamine's mechanisms has spurred drug discovery for agents with similar efficacy but fewer side effects. Efforts include identifying active circulating substances after ketamine administration and agents targeting its mechanisms. Clinical trials are ongoing, and in 2022, AUVELITY™ (dextromethorphan with bupropion) was FDA-approved. Future development aims for safer, rapidly acting antidepressants as potent as ketamine.