Promising new pharmacological targets for depression: The search for efficacy

Pharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD path...

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Bibliographic Details
Published in:Drug discovery today 2023-12, Vol.28 (12), p.103804, Article 103804
Main Authors: Tsugiyama, Lucila Emiko, Macedo Moraes, Ruan Carlos, Cavalcante Moraes, Yaslle Andrade, Francis-Oliveira, Jose
Format: Article
Language:English
Subjects:
Antidepressive Agents - pharmacology
Antidepressive Agents - therapeutic use
Depression
Depressive Disorder, Major - drug therapy
Humans
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Summary:Pharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD, as well as the preclinical and clinical evidence for an antidepressant effect of molecules that target non-serotonergic systems. We offer some insights into the challenges facing the development of new antidepressant drugs, and the prospect of finding more effectiveness for each target discussed.
ISSN:1359-6446
1878-5832
1878-5832
DOI:10.1016/j.drudis.2023.103804