Journal
CURRENT PSYCHIATRY REPORTS
Volume 14, Issue 6, Pages 643-649Publisher
SPRINGER
DOI: 10.1007/s11920-012-0321-8
Keywords
Major depressive disorder; Treatment-resistant depression; Antidepressant; Drug discovery; Psychopharmacology; Glutamate; Ketamine; N-methyl-d-aspartate receptor; Mood disorders; Psychiatry
Categories
Funding
- National Institute of Mental Health [K23MH094707]
- Brain and Behavior Research Foundation (NARSAD)
- American Foundation for Suicide Prevention
- Evotec Neurosciences
- Janssen Research Development
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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 similar to 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.
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