A
Caroline Ashley, Aileen Dunleavy, John Cunningham in The Renal Drug Handbook, 2018
The effects of renal function on agomelatine pharmacokinetics were investigated in a study of healthy subjects and patients with severe impaired renal function. In the renal impairment patients, exposure to agomelatine increased more than 25% compared to healthy subjects. The available safety data from the clinical trials did not demonstrate any significant tolerability or safety issues with the use of agomelatine compared to placebo among patients with mildly to moderately impaired renal function. Although agomelatine can be used in patients with renal impairment, such patients should be monitored more closely. (Howland RH. Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults. Neuropsychiatr Dis Treat. 2009; 5: 563–76.)
Cycling
Ira Glick, Danielle Kamis, Todd Stull in The ISSP Manual of Sports Psychiatry, 2018
Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments in mainstream practice, but concerns about QTc prolongation are more significant at the extremes of physical exertion. This makes sertraline a good first choice for many cyclists. Agomelatine should also be considered as it has a favorable side-effect profile and a half-life that results in few, if any, “hangover” effects (McAllister-Williams & Johnston, 2016). Regular liver function monitoring is a requirement but, again, this can be delegated. Bupropion is an uncommonly prescribed antidepressant in practice. Potential improvements in aerobic performance in hot conditions have been reported that would have direct relevance in many cycling events (Watson, Hasegawa, Roelands, Piacentini, Looverie, & Meeusen, 2005) and, as a consequence, this drug is under review as a performance-enhancing agent (http://list.wada-ama.org/list/s6-stimulants/).
Generalized Anxiety Disorder
Stephen M. Stahl, Bret A. Moore in Anxiety Disorders: A Guide for Integrating Psychopharmacology and Psychotherapy, 2013
One new approach is the drug agomelatine, an agonist at melatonergic (MT1, MT2) receptors and an antagonist at 5HT2C serotonergic receptors. It has no effect on monoamine uptake and no affinity for adrenergic, histaminergic, cholinergic, dopaminergic, BZD receptors, or other serotonergic receptors. During clinical trials in which it was tested for antidepressant efficacy, it showed some anxiolytic action and was assessed for GAD (at 25–50 mg/day) in a randomized, placebo-controlled 12-week study (D. J. Stein, Ahokas, & de Bodinat, 2008). Agomelatine decreased the HAM-A total score significantly more than placebo. Although both psychic and somatic scores declined, only the latter decline reached statistical significance relative to placebo. Significantly more patients responded to the drug than to placebo (66.7& vs. 46.6&, respectively), and significantly more remitted under the drug (41.3& vs. 22.4&). Very few patients withdrew from the study (three out of 55 from placebo and five out of 63 from agomelatine), and adverse events were minimal (mainly dizziness, 7.9& vs. 3.4&, and nausea, 4.8& vs. 1.7&, for agomelatine compared to placebo). Considering the high baseline HAM-A score of ≥22, the outcome indicates that agomelatine may have anxiolytic benefit.
Prospects for circadian treatment of mood disorders
Published in Annals of Medicine, 2018
Anisja Hühne, David K. Welsh, Dominic Landgraf
Agomelatine is a recently developed antidepressant drug available for use in Europe. It acts as an agonist at melatonin receptors MT1 and MT2 and an antagonist at the serotonin 5-HT2C receptor. Antidepressant actions of agomelatine have been attributed to various mechanisms including adjustment of circadian rhythms. In diurnal and nocturnal rodents, agomelatine expedites resynchronization of behaviour after shifts in the light-dark cycle [142,143]. Furthermore, it is able to adjust the phase of sleep–wake cycles in rodents under entrained conditions [144], increases the amplitude of melatonin and body temperature rhythms [145], and can synchronize rats to a 24 h schedule when administered in daily doses under constant environmental conditions [146]. Thus, agomelatine has a strong impact on the circadian system.
Alopecia associated with agomelatine use: a case report
Published in Psychiatry and Clinical Psychopharmacology, 2018
Ibrahim Gundogmus, Mustafa Ispir, Abdulkadir Karagoz, Ayhan Algul, Servet Ebrinc
Antidepressant drugs may cause skin lesions such as urticaria, photosensitivity, alopecia, pruritus, eruptions, pruritus, acne, and dryskin. This type of dermatological side effects have been most frequently reported with escitalopram, sertraline, tricyclic antidepressants, and venlafaxine use [1]. Agomelatine, which is known with have fewer side effects from other antidepressants, is an antidepressant with a novel mechanism of action. Agomelatine that represents an innovative approach to treating depression is a selective melatonergic MT1/MT2 receptor agonist and serotonin 5-HT2c and 5-HT2b receptor antagonist [2]. It is thought that antidepressant activity of agomelatine is associated with the synergy between both types of receptors, which are parts of the circadian rhythm, while generally antidepressants act via the inhibition of the reuptake of serotonin and noradrenaline and result in increases in serotonin and noradrenaline in the central nervous system [3]. Agomelatine has shown to be as effective which is similar to that of standard antidepressants in patients with major depressive disorders [4]. It was reported to improve disturbed sleep-wake cycles throughout the night in patients with depressive disorders and low risk of sexual side effects, insomnia, and withdrawal symptoms on discontinuation make it an alternative for the management of depression [5,6].
The preclinical discovery and development of agomelatine for the treatment of depression
Published in Expert Opinion on Drug Discovery, 2020
George Konstantakopoulos, Stefanos Dimitrakopoulos, Panayiota G. Michalopoulou
There has been an ongoing debate on the role of agomelatine in the treatment of depression. Its unique mechanism of action offers an alternative to monoaminergic antidepressants, especially for patients that are non-responders or experience side-effects that cannot be tolerated. Moreover, recent meta-analytic studies including large sample sizes suggest that agomelatine is a justified first-line choice for managing depression. However, its long-term efficacy is not yet well established and more studies examining its effect on relapse prevention are needed. Although agomelatine has a favorable safety and tolerance profile, the issue of hepatotoxicity and regular blood monitoring still raises clinician concern. Moreover, further exploration of agomelatine’s potential for the treatment of anxiety disorders, depression co-morbid with physical illness, and other mental disorders is also justified by the initial findings.
Related Knowledge Centers
- Generalized Anxiety Disorder
- Liver Disease
- Major Depressive Disorder
- Major Depressive Episode
- Dementia
- Atypical Antidepressant
- Serotonin Receptor Antagonist
- Melatonin Receptor Agonist
- Placebo-Controlled Study
- Effect Size