Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms

Ketamine is an open channel blocker of ionotropic glutamatergic N-Methyl-D-Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects in patients with depression and treatment-resistant depression fostered novel effective treatments for mood disorders. This discovery not only provided new insight into the neurobiology of mood disorders but also uncovered fundamental synaptic plasticity mechanisms that underlie its treatment. In this review, we discuss key clinical aspects of ketamine's effect as a rapidly acting antidepressant, synaptic and circuit mechanisms underlying its action, as well as how these novel perspectives in clinical practice and synapse biology form a road map for future…

• UD
  U.S. Department of Veterans Affairs
• A
  AstraZeneca
• YU
  Yale University
• B
  Biogen
• NP
  Novartis Pharmaceuticals Corporation
• OA
  Otsuka America Pharmaceutical
• S
  Sunovion
• JP
  Jazz Pharmaceuticals
• NB
  Neurocrine Biosciences
• OA
  Otsuka America
• E
  Eisai
• OO
  Office of Academic Affiliations, Department of Veterans Affairs
• NC
  National Center for PTSD, U.S. Department of Veterans Affairs
• NI
  National Institute on Alcohol Abuse and Alcoholism

  Award: 2P50AA012870
• NI
  National Institute of Mental Health

  Awards: MH081060, MH070727, MH066198
• YC
  Yale Center for Clinical Investigation, Yale School of Medicine

  Award: 2UL1TR001863