Agomelatine for depression: expanding the horizons?

Norman, Trevor R.; Olver, James S

doi:10.1080/14656566.2019.1574747

Cited by 48 publications

(28 citation statements)

References 71 publications

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“…In older persons, however, mirtazapine should be prescribed with caution: a large observational study found that mirtazapine use was associated with a higher adverse event rate than other antidepressants [6]. One of the newest antidepressants, agomelatine, is an antidepressant with unique pharmacological features; it is a melatonin agonist and a selective serotonin antagonist [38]. The first antidepressant with activity on melatonin and serotonin receptors.…”

Section: Sedation Sleep Disturbance Deliriummentioning

confidence: 99%

Depression, antidepressants and fall risk: therapeutic dilemmas—a clinical review

Poelgeest¹,

Pronk²,

Rhebergen

et al. 2021

Eur Geriatr Med

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Purpose The aim of this clinical review was to summarize the existing knowledge on fall risk associated with antidepressant use in older adults, describe underlying mechanisms, and assist clinicians in decision-making with regard to (de-) prescribing antidepressants in older persons. Methodology We comprehensively examined the literature based on a literature search in Pubmed and Google Scholar, and identified additional relevant articles from reference lists, with an emphasis on the most commonly prescribed drugs in depression in geriatric patients. We discuss use of antidepressants, potential fall-related side effects, and deprescribing of antidepressants in older persons. Results Untreated depression and antidepressant use both contribute to fall risk. Antidepressants are equally effective, but differ in fall-related side effect profile. They contribute to (or cause) falling through orthostatic hypotension, sedation/impaired attention, hyponatremia, movement disorder and cardiac toxicity. Falling is an important driver of morbidity and mortality and, therefore, requires prevention. If clinical condition allows, withdrawal of antidepressants is recommended in fall-prone elderly persons. An important barrier is reluctance of prescribers to deprescribe antidepressants resulting from fear of withdrawal symptoms or disease relapse/recurrence, and the level of complexity of deprescribing antidepressants in older persons with multiple comorbidities and medications. Practical resources and algorithms are available that guide and assist clinicians in deprescribing antidepressants. Conclusions (De-) prescribing antidepressants in fall-prone older adults is often challenging, but detailed insight in fall-related side effect profile of the different antidepressants and a recently developed expert-based decision aid STOPPFalls assists prescribers in clinical decision-making.

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Section: Sedation Sleep Disturbance Deliriummentioning

confidence: 99%

Depression, antidepressants and fall risk: therapeutic dilemmas—a clinical review

Poelgeest¹,

Pronk²,

Rhebergen

et al. 2021

Eur Geriatr Med

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“…In the eye, melatonin serves several functions; it exerts antiapoptotic and antioxidant activities and, in particular, decreases IOP, thus suggesting that melatonin or its analogues could be used to treat glaucoma [1]. In particular, topical application of saline formulations of melatonin or melatonin analogues such as methoxycarbonylamino-N-acetyltryptamine or agomelatine (commonly used as anti-depressant) [11] significantly reduces IOP [12][13][14]. Both melatonin and agomelatine have higher efficacy in reducing IOP in hypertensive than in normotensive eyes, suggesting that melatonin and its analogues can have a more effective hypotensive activity when hypertensive glaucoma is established [12,14].…”

Section: Introductionmentioning

confidence: 99%

Hypotensive Effect of Nanomicellar Formulation of Melatonin and Agomelatine in a Rat Model: Significance for Glaucoma Therapy

Monte

Cammalleri

Pezzino³

et al. 2020

Diagnostics

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Background: Melatoninergic agents are known to reduce intraocular pressure (IOP). The present study was performed to evaluate the effect of nanomicellar formulations of melatoninergic agents on IOP in the rat. Methods: Tonometry was used to measure IOP in eyes instilled with melatonin or agomelatine. Ocular hypertension was induced by the injection of methylcellulose in the anterior chamber. Results: Melatonin formulated in nanomicelles had a longer lasting hypotonizing effect on IOP with respect to melatonin in saline. Nanomicellar formulations of melatonin and agomelatine, either alone or in combination, had lowering effects that did not depend on their concentration or their combination, which, however, resulted in an increased duration of the hypotonizing effect. The duration of the lowering effect was further increased by the addition of lipoic acid. Conclusions: We demonstrated the effective hypotonizing activity of melatonin and agomelatine in combination with lipoic acid. Although results in animals cannot be directly translated to humans, the possibility of developing novel therapeutical approaches for patients suffering from hypertensive glaucoma should be considered.

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“…Agomelatine is a synthetic analog of MEL and acts as an agonist on the MT1 and MT2 receptors. Agomelatine also acts as an antagonist on the 5-HT2C receptors and has a low affinity for most other receptors, including adrenoceptors, dopamine, GABA, muscarinic, histamine, benzodiazepine, and sigma receptors, as well as ion channels (Norman and Olver, 2019). We selected a list of genes specific to agomelatine action that formed twelve significant downregulated pathways.…”

Section: Clinical Modelmentioning

confidence: 99%

Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression

Dmitrzak‐Węglarz

Banach²,

Bilska

et al. 2021

Front. Pharmacol.

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Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.

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Agomelatine for depression: expanding the horizons?

Cited by 48 publications

References 71 publications

Depression, antidepressants and fall risk: therapeutic dilemmas—a clinical review

Depression, antidepressants and fall risk: therapeutic dilemmas—a clinical review

Hypotensive Effect of Nanomicellar Formulation of Melatonin and Agomelatine in a Rat Model: Significance for Glaucoma Therapy

Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression

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