Sleep Better Than Melatonin? Agomelatine – A Melatonin Alternative (Research)
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Agomelatine is an antidepressant which was first approved in Europe in 2009 . Its main mechanism of action includes agonist at melatonergic (MT1 and MT2) receptors and antagonist at serotonergic 5-HT2C receptor. Animal studies including Vogel conflict procedure, elevated plus-maze procedure, conditioned footshock-induced ultrasonic vocalizations test, social defeat stress test, predator stress test, and the fear learning process suggested anxiolytic properties of agomelatine [12-14]. Studies further showed that agomelatine’s anxiolytic property is mainly attributed from its 5-HT2C antagonism, but melatonin receptor may also be involved in decreasing anxiety . In line with animal models, a study initially showed that agomelatine was effective in treating anxiety symptoms associated with depression . Therefore, numerous randomized, double-blinded, placebo-controlled clinical trials (RCTs) demonstrated that agomelatine could be an effective and safe treatment option for patients with GAD [17,18].
Antidepressants are widely used in the treatment of MDD. In addition, antidepressants have several effects on sleep: in short-term treatment, many activating antidepressant effects may disrupt sleep, while others with sedative properties rapidly improve sleep; however, all antidepressants should normalize sleep in the long-term treatment.13 Agomelatine, as a novel antidepressant for the treatment of MDD, could quickly improve the disturbed sleep-wake cycles,14 sleep efficiency, and correcting the circadian rhythm abnormalities,15 with a promising role for the treatment of sleep disorders associated with MDD.16 In addition, the melatonin (MT) receptor agonists are now appearing as the new promising treatment options for sleep and circadian-rhythm-related disorders, such as agomelatine and ramelteon.17 Being the MT1 and MT2 receptors agonists, agomelatine is also an antagonist that affects the 5-hydroxytryptamine-2C (5HT2c) receptors. Since agomelatine acts on the suprachiasmatic nucleus, hippocampus, frontal cortex, and the striatum, it could lead to the improvement of both the sleep and mood.18,19 There are distinctive differential binding affinities to MT1 versus MT2: Agomelatine binds to MT1 and MT2 receptors with approximately equal affinity and additional antagonist properties at the 5‐HT2c receptors, and ramelteon exhibits a 10‐fold greater affinity for MT1 than MT2.20,21 This might explain why there are differences in the effect of facilitations in sleep-onset between these two medications. However, problems of the sleep-wake cycle and circadian rhythm would be corrected by the usage of agomelatine.15,16 However, there has been little research done on the association between agomelatine and the usage of sedative-hypnotics. This study aimed to test the hypothesis as to whether being treated with agomelatine is less likely to be co-treated with sedative hypnotic agents. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384877/
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