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Cited by 605

The DOI matches its Crossref record; 171 of the 171 references it cites were found in a registry or an index.

A brief history of the development of antidepressant drugs: From monoamines to glutamate.

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Hillhouse, Todd M., Porter, Joseph H.·2015·Experimental and Clinical Psychopharmacology

Abstract

Major depressive disorder (MDD) is a chronic, recurring, and debilitating mental illness that is the most common mood disorder in the United States. It has been almost 50 years since the monoamine hypothesis of depression was articulated, and just over 50 years since the first pharmacological treatment for MDD was discovered. Several monoamine-based pharmacological drug classes have been developed and approved for the treatment of MDD; however, remission rates are low (often less than 60%) and there is a delayed onset before remission of depressive symptoms is achieved. As a result of a "proof-of-concept" study in 2000 with the noncompetitive NMDA antagonist ketamine, a number of studies have examined the glutamatergic systems as viable targets for the treatment of MDD. This review will provide a brief history on the development of clinically available antidepressant drugs, and then review the possible role of glutamatergic systems in the pathophysiology of MDD. Specifically, the glutamatergic review will focus on the N-methyl-D-aspartate (NMDA) receptor and the efficacy of drugs that target the NMDA receptor for the treatment of MDD. The noncompetitive NMDA receptor antagonist ketamine, which has consistently produced rapid and sustained antidepressant effects in MDD patients in a number of clinical studies, has shown the most promise as a novel glutamatergic-based treatment for MDD. However, compounds that target other glutamatergic mechanisms, such as GLYX-13 (a glycine-site partial agonist at NMDA receptors) appear promising in early clinical trials. Thus, the clinical findings to date are encouraging and support the continued search for and the development of novel compounds that target glutamatergic mechanisms.

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Metadata

Authors
Hillhouse, T. M., & Porter, J. H.
Venue
Experimental and Clinical Psychopharmacology
Published
2015-02
Volume
23
Issue
1
Pages
1-21
ISSN
  • 1064-1297 (ISSN-L)
  • 1936-2293
OpenAlex
W2048175288
Cited by
605
References
171
FWCI
12.06
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: A brief history of the development of antidepressant drugs: From monoamines to glutamate. https://app.cochat.ai/papers/10.1037/a0038550
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Hillhouse, T. M., & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: From monoamines to glutamate. Experimental and Clinical Psychopharmacology. https://doi.org/10.1037/a0038550

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