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Cited by 334Treatment of Major DepressionCircadian rhythm and melatoninTryptophan and brain disorders

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Novel melatonin-based therapies: potential advances in the treatment of major depression

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Hickie, Ian B, Rogers, Naomi L·2011·The Lancet
DOI 10.1016/s0140-6736(11)60095-0
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Abstract

Major depression is one of the leading causes of premature death and disability. Although available drugs are effective, they also have substantial limitations. Recent advances in our understanding of the fundamental links between chronobiology and major mood disorders, as well as the development of new drugs that target the circadian system, have led to a renewed focus on this area. In this review, we summarise the associations between disrupted chronobiology and major depression and outline new antidepressant treatment strategies that target the circadian system. In particular, we highlight agomelatine, a melatonin-receptor agonist and selective serotonergic receptor subtype (ie, 5-HT(2C)) antagonist that has chronobiotic, antidepressant, and anxiolytic effects. In the short-term, agomelatine has similar antidepressant efficacy to venlafaxine, fluoxetine, and sertraline and, in the longer term, fewer patients on agomelatine relapse (23·9%) than do those receiving placebo (50·0%). Patients with depression treated with agomelatine report improved sleep quality and reduced waking after sleep onset. As agomelatine does not raise serotonin levels, it has less potential for the common gastrointestinal, sexual, or metabolic side-effects that characterise many other antidepressant compounds.

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  • Agomelatine is a non-sedative antidepressant that acts as an agonist at melatonergic M1 and M2 receptors and an antagonist at serotonergic 5-HT2C receptors.

    “Agomelatine is a non-sedative antidepressant drug exerting agonistic action at melatonergic M1 and M2 receptors, and antagonistic action at serotonergic 5HT2creceptors [24].”

    From Effects of Antidepressants on Sleep (2017) · cites this paper as [24]

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Metadata

Authors
Hickie, I. B., & Rogers, N. L.
Affiliations
The University of Sydney (AU)
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2011-08
Volume
378
Issue
9791
Pages
621-631
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(11)60095-0
OpenAlex
W2107278158
Cited by
334
References
18
Citations by year
2026: 5 · 2025: 18 · 2024: 22 · 2023: 16 · 2022: 9 · 2021: 20 · 2020: 12 · 2019: 15 · 2018: 12 · 2017: 26 · 2016: 15 · 2015: 31 · 2014: 39 · 2013: 38 · 2012: 45
FWCI
4.72
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
major depressive disorder, melatonin, agomelatine, chronobiology, circadian rhythm, antidepressants, 5-HT2C receptor antagonist, melatonin receptor agonists, sleep quality, relapse prevention, anxiolytic effects, venlafaxine, fluoxetine, sertraline
MeSH terms
Acetamides, Antidepressive Agents, Circadian Rhythm, Major Depressive Disorder, Humans, Melatonin, Naphthalenes, Sleep, Chronobiology Disorders

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