title: Is there anything really novel on the antidepressant horizon?
abstract: Major depression represents one of the most disabling illnesses worldwide and current treatments are only partially effective. All antidepressant agents modulate the monoamine system, which likely accounts for the similar efficacy profile of available treatments. Herein we summarize the current state of depression therapeutics and assess the antidepressant development pipeline. Antidepressant response rates in controlled trials are estimated at ~54 % and real-world effectiveness data suggests a somewhat lower rate. Response rates are lower still in patients who have not responded to previous treatment attempts and meaningful advancements will likely come only from identification of mechanistically novel agents. Monoaminergic agents largely dominate the antidepressant development pipeline, however the glutamate neurotransmitter system represents a bright spot on the antidepressant horizon. We review in detail findings regarding the antidepressant effects of the glutamate N-methyl-d-aspartate receptor antagonist ketamine in order to highlight the promise of novel agents as future treatments for major depression.
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1230, New York, NY 10029, USA. james.murrough@mssm.edu
authors.forename: James W
authors.initials: JW
authors.lastname: Murrough
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D055808:Drug Discovery / Q000639:trends; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine