Cited by 29Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorPsychological Treatments and Disorders

Rational site-directed pharmacotherapy for major depressive disorder

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Blier, Pierre·2014·The International Journal of Neuropsychopharmacology

Abstract

It is now accepted that major depressive disorder (MDD) is not a single pathophysiological entity. It is therefore not surprising that remission rates to a first antidepressant trial are low. In addition, antidepressants may target various neuronal elements for which there are gene polymorphisms, such as the serotonin (5-HT) reuptake transporter, which may modulate response. Acting on a single monoaminergic target, such as inhibiting the 5-HT transporter, may confer efficacy in MDD, but other targets may be used and/or combined in treatment-resistant patients. These include the blockade of norepinephrine transporters, monoamine oxidase, 5-HT(2A), 5-HT(1B) and 5-HT7 receptors, and the activation of 5-HT(1A) and dopamine 2 receptors. While antidepressants may have more than one of these properties, so do atypical antipsychotics. When using the latter medications, however, their regimens should be below those effective in treating psychosis to avoid dopamine 2 antagonism, which could be counter-productive in MDD. In some patients, combining medications from treatment initiation may also provide additional therapeutic benefits.

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Crossref · 10.1017/s1461145713000400

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  • By broadly enhancing serotoninergic transmission, SSRI drugs activate gamma-aminobutyric acid interneurons, thereby dampening noradrenergic and dopaminergic input.

    “By broadly enhancing serotoninergic transmission, SSRI drugs activate gamma-aminobutyric acid (GABA) interneurons, thereby dampening the noradrenergic as well as the dopaminergic input (Blier, 2014).”

    From Effectiveness of Vortioxetine on Emotional Blunting in Patients with Major Depressive Disorder with inadequate response to SSRI/SNRI treatment (2021) · cites this paper as Blier, 2014

    In “Possible reasons for low remission rates with a first antidepressant trials” (page unavailable), the paper describes serotonin activating GABA neurons that inhibit noradrenergic and dopaminergic neuron firing. It qualifies the SSRI effect on dopamine, however: decreased dopaminergic firing has not been reported with all SSRIs. The claim presents that effect as general to SSRI drugs. (LLM, conf=0.88)

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Research works printed but not linked: 1

  1. World Health Organization (2008) The global burden of disease: 2004 update, part 4, pp. 40-51. Geneva: WHO.

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Authors
Blier, P.
Affiliations
Institute of Mental Health Research (CA)
Corresponding author
Blier, Pierre
Venue
The International Journal of Neuropsychopharmacology
Published
2013-06-10
Volume
17
Issue
07
Pages
997-1008
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
OpenAlex
W2119211687
Cited by
29
References
87
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 2
FWCI
0.29
Type
journal article
Language
en
Open access
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Social Sciences › Psychology › Clinical Psychology › Psychological Treatments and Disorders
Keywords
major depressive disorder, pharmacotherapy, antidepressant response, treatment-resistant depression, genetic polymorphism, serotonin transporter, norepinephrine transporter, monoamine oxidase, serotonin receptors, dopamine D2 receptor, atypical antipsychotics, combination therapy
MeSH terms
Animals, Antidepressive Agents, Clinical Trials as Topic, Depressive Disorder, Major, Major Depressive Disorder, Drug Therapy, Combination, Humans, Polypharmacy

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