Agomelatine, a novel intriguing antidepressant option enhancing neuroplasticity: A critical review

Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Venturini, Paola; Fusar‐Poli, Paolo; Sher, Leo; Amore, Mario; Girardi, Paolo

doi:10.3109/15622975.2013.765593

Cited by 70 publications

(63 citation statements)

References 95 publications

(107 reference statements)

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“…All patients completed the study, in line with the good tolerability profile of agomelatine [17]. This observation makes agomelatine a promising choice as a first-line agent for the treatment of apathy in people with bv-FTD.…”

Section: Discussionmentioning

confidence: 65%

“…Agomelatine has been shown to be effective in the treatment of a number of psychiatric disorders including major depression, chronic fatigue and sleep disorders [17,20]. Our data suggest that agomelatine could also be a useful treatment option for neuropsychiatric symptoms in subjects with other neurodegenerative conditions such as Parkinson's disease [19].…”

Section: Discussionmentioning

confidence: 86%

“…Excitatory 5-HT2C receptors keep GABA interneurons activated, enhancing tonic inhibitory control of monoaminergic neurons in these nuclei. Agomelatine thus indirectly increases the noradrenergic and dopaminergic tone in the prefrontal cortices, reducing the activity of GABA interneurons via 5-HT2C antagonism [17]. …”

Section: Discussionmentioning

confidence: 99%

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Agomelatine Improves Apathy in Frontotemporal Dementia

et al. 2016

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Background/Aims: Apathy is the most common initial symptom of frontotemporal dementia (FTD) and has been linked to frontal-subcortical dopaminergic system dysfunction. No pharmacological therapy has been approved for the treatment of apathy, but, on the basis of its physiopathological mechanism, we suspected that increasing prefrontal dopaminergic innervation could improve this disabling symptom. Methods: We evaluated a group of 24 nondepressed patients with a diagnosis of the behavioral variant of FTD, in order to determine the effectiveness on apathy of agomelatine, an antidepressant with MT1 and MT2 receptor agonism and 5-HT2C receptor antagonism; the latter leads to an increase in prefrontal dopaminergic and noradrenergic tone. To try to tease out the effects of 5-HT2C antagonism on apathy, patients were randomized, using a cross-over design, to receive either agomelatine 50 mg/day or sustained release melatonin 10 mg/day for 10 weeks in a double-blind procedure. At the end of the follow-up period, subjects receiving melatonin switched to agomelatine for the following 10 weeks. Results: Agomelatine, but not melatonin, was associated with a significant reduction of apathy in FTD subjects and of caregiver distress due to patients' apathy. The switch from melatonin to agomelatine was associated with a reduction in apathetic behavior. Agomelatine was well-tolerated by all enrolled subjects. Conclusions: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 86%

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Agomelatine Improves Apathy in Frontotemporal Dementia

et al. 2016

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“…The antidepressive effects of melatonin that have been previously described [38][39][40] are mediated by inhibition of Asm and a reduction of ceramide as revealed in genetic studies using Asm-deficient mice. These mice fail to respond to melatonin with changes of the stressed and depressive behavior.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System

Hoehn

Monse²,

Pohl³

et al. 2016

Neurosignals

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Background: Melatonin has been shown to have antidepressive effects. We tested whether melatonin inhibits the acid sphingomyelinase/ceramide system and mediates its antidepressive effects via inhibition of the acid sphingomyelinase and a reduction of ceramide in the hippocampus. Antidepressants such as amitriptyline and fluoxetine were previously shown to inhibit the acid sphingomyelinase/ceramide system, which mediates neurogenesis and behavioral changes induced by these drugs. Methods: The effect of melatonin on the activity of the acid sphingomyelinase prior to and after treatment with melatonin was determined in cultured neurons and in vivo in the hippocampus of mice by measuring the consumption of [¹⁴C] sphingomyelin. Ceramide was measured by DAG kinase assay and fluorescence microscopy of the hippocampus and of cultured neurons. Neurogenesis in the hippocampus was analyzed by in vivo labeling with bromodeoxyuridine. Behavior was assessed in standardized tests. Results: Melatonin treatment inhibited acid sphingomyelinase in vitro in cultured pheochromocytoma cells and in vivo in the hippocampus, which resulted in a reduction of ceramide in vitro and in vivo. The inhibition of the acid sphingomyelinase/ceramide system translated into increased neurogenesis in glucocorticosterone-stressed mice after treatment with melatonin, an effect that is abrogated in acid sphingomyelinase-deficient mice. Likewise, melatonin improved the depressive behavior of stressed mice, a therapeutic effect that was again absent in acid sphingomyelinase-deficient animals. Conclusion: These data indicate that the antidepressive effects of melatonin as well as the induction of neurogenesis triggered by this drug are mediated by an inhibition of the acid sphingomyelinase/ceramide system. This is the first study to identify melatonin as an inhibitor of the acid sphingomyelinase.

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“…Concerns about antidepressants' efficacy and tolerability in patients with major depressive disorder have led to investigating newer agents with alternative mechanism of action, such as agents that enhance neuroplasticity and neurogenesis 11. These concerns have also led to increased interest in non-pharmacological treatments for depression.…”

Section: Introductionmentioning

confidence: 99%

Non-pharmacological treatment of depression: a systematic review and evidence map

et al. 2016

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Agomelatine, a novel intriguing antidepressant option enhancing neuroplasticity: A critical review

Abstract: Agomelatine actually represents an intriguing option in the treatment of affective disorders.

Cited by 70 publications

References 95 publications

Agomelatine Improves Apathy in Frontotemporal Dementia

Agomelatine Improves Apathy in Frontotemporal Dementia

Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System

Non-pharmacological treatment of depression: a systematic review and evidence map

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