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Review
. 2017 May;4(5):409-418.
doi: 10.1016/S2215-0366(17)30015-9. Epub 2017 Jan 31.

How do antidepressants work? New perspectives for refining future treatment approaches

Catherine J Harmer  1 , Ronald S Duman  2 , Philip J Cowen  3
Affiliations
Review

How do antidepressants work? New perspectives for refining future treatment approaches

Catherine J Harmer et al. Lancet Psychiatry. 2017 May.

Abstract

Most currently available antidepressants target monoamine neurotransmitter function. However, a purely neurotransmitter-based explanation for antidepressant drug action is challenged by the delayed clinical onset of most agents and the need to explain how neurochemical changes reverse the many different symptoms of depression. Novel approaches to understanding of antidepressant drug action include a focus on early changes in emotional and social processing and the role of neural plasticity. In this Review, we discuss the ways in which these two different theories reflect different or complementary approaches, and how they might be integrated to offer novel solutions for people with depression. We consider the predictions made by these mechanistic approaches for the stratification and development of new therapeutics for depression, and the next steps that need to be made to facilitate this translation of science to the clinic.

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Figures

Figure 1
Figure 1. The neurotrophic theory of antidepressant drug action
NMDA=N-methyl-D-aspartate receptor. GABAA=γ-aminobutyric acid receptor. Ach-M=acetylcholine muscarinic receptor. AMPA=α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. VDCC=voltage dependent calcium channel. SSRI=selective serotonin reuptake inhibitor. SNRI=serotonin-norepinephrine reuptake inhibitor. SERT=serotonin transporter. NET=norepinephrine transporter. BDNF=brain-derived neurotrophic factor. HPA=hypothalamic-pituitary-adrenal.
Figure 2
Figure 2. The cognitive neuropsychological theory of antidepressant drug action
Possible interactions with plasticity changes and induced with antidepressant drug treatments are shown.
See this image and copyright information in PMC

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