Agomelatine: Characteristics And Side Effects Of This Antidepressant
Today there are many pharmacological tools to treat people who suffer from a depressive disorder. Among antidepressant drugs, the presence of agomelatine stands out, a special compound due to its particular mechanism of action and its chemical profile, very similar to that of melatonin, a hormone related to circadian rhythms of sleep.
In this article we explain what is agomelatine what are its clinical uses and its mechanism of action, its main side effects and its uses in other disorders apart from depression.
Agomelatine is an atypical antidepressant drug used to treat major depressive disorder This medication was developed by the French pharmaceutical company Servier and was approved for use in Europe in 2009, and in Australia in 2010. This drug is considered to be an analogue of melatonin.
Clinical studies carried out with agomelatine indicate that it is a valid drug to treat depressive episodes in adults. Its antidepressant effect is more powerful in severe depression, and it has also been shown to be at least as effective as some selective serotonin reuptake inhibitors (paroxetine, sertraline, escitalopram or fluoxetine) in the treatment of major depression.
On the other hand, in a meta-analysis carried out in 2018 in which 21 antidepressant drugs were compared, it was concluded that agomelatine was one of the most tolerable and effective drugs. Not in vain and as we will see below, its particular mechanism of action, through which is capable of modulating circadian rhythms makes it especially unique in terms of its pharmacological profile.
The mechanism of action of melatonin is quite peculiar within the group of antidepressants. This medicine exerts its therapeutic effects by acting as an agonist of melatonin receptors (MT1 and MT2) and as an antagonist of serotonin receptors (5-HT2c and 5-HT2b).
The studies carried out indicate that it has no effect on the absorption of monoamines and does not have affinity for adrenergic, histamine, cholinergic, dopaminergic and serotonergic receptors, as occurs with other antidepressants.
A particular characteristic of agomelatine is its ability to modulate or resynchronize circadian rhythms. In studies with animal models, it has been proven to have positive effects in cases where there is delayed sleep phase syndrome, a disorder that affects the quality and type of sleep, the rhythm of body temperature, the hormonal rhythm, among other biological functions.
On the other hand, agomelatine increases the release of the neurotransmitters dopamine and norepinephrine, especially in regions of the frontal cerebral cortex, due to its action as an antagonist of serotonergic receptors (specifically, 5-HT2c). This is why this drug is sometimes classified as a norepinephrine and dopamine deinhibitor antidepressant. Furthermore, the antagonistic effect on the 5-HT2b receptor is a property that it shares with various atypical antipsychotic drugs (e.g. aripiprazole), which are also used as antidepressants).
Currently, various research focuses on studying the usefulness of drugs that antagonize the 5-HT2b receptor to reduce headaches (in migraines and migraines, for example). Therefore, it should be noted that this antagonistic effect of agomelatine has been shown to be useful for its depressive effectiveness, but also for its ability to reduce the adverse effects of the drug.
Side effects
One of the advantages of agomelatine is that produces fewer side and adverse effects than the vast majority of antidepressant drugs Agomelatine does not alter attention span or memory. Furthermore, in depressed patients its use increases slow-wave sleep without modifying the amount of REM sleep (rapid eye movements) or REM latency.
Due to its characteristic pharmacological profile, agomelatine induces an advance in sleep onset time and minimum heart rate Furthermore, from the first week of treatment with agomelatine, patients report an increase in the onset time and quality of sleep, without causing alterations in mobility (e.g. daytime clumsiness).
However, the use of agomelatine is not free of possible side effects. More serious, but also rare, adverse reactions include migraine, restless legs syndrome, eczema, excessive sweating, agitation, irritability or even aggressive or self-harming behaviors. And among the most common, we can highlight the following:
Effects of agomelatine on seasonal affective disorder
Seasonal affective disorder is a subtype of major depressive or bipolar disorder which is characterized by recurrent affective episodes in the same season of the year. Patients most often suffer from depressive episodes during the fall or winter, which are followed by remission or hypomanic episodes. These people show a delay
As we have mentioned, research suggests that agomelatine could have beneficial effects on sleep disturbances and circadian rhythms. In a study published in 2007 in the journal Psychopharmacology, people treated with this drug noticed its effects after 2 weeks, with a notable reduction in the symptoms associated with the syndrome (mood changes, sleeping difficulties, and others).
In this study, agomelatine showed excellent tolerability at a dose of 25 mg, without significant side effects typical of other antidepressant drugs. About a third of patients noted slight drowsiness after taking the medication; however, only one patient experienced subjective deterioration (due to fatigue) during the first 5 days.
Uses of this drug for anxiety
The clinical uses of agomelatine go beyond depressive symptoms, as has been observed in the different studies that have been carried out in recent years. In various investigations it has been proven that the anxiolytic efficacy of agomelatine It is more powerful in depressed patients who suffer from severe anxiety symptoms
In a meta-analysis of six multicenter studies that included almost 2,000 patients with major depressive disorder, more than 900 of them suffered from severe anxiety symptoms. The clinical efficacy of agomelatine was compared with selective serotonin reuptake inhibitors (sertraline and fluoxetine), and with a serotonin and norepinephrine reuptake inhibitor (venlafaxine), as well as placebo.
The results of the analysis concluded that agomelatine significantly reduces anxiety symptoms, starting from the second week of treatment, and more effectively than the rest of the antidepressants. Furthermore, the positive effects were even more pronounced in people with depression who also suffered from high anxiety.
In short, agomelatine has not only been shown to be an effective drug against depressive symptoms, but also in cases in which there is comorbid anxiety, and also in people with circadian rhythm disorders, as we mentioned previously. For all this, clinical interest in the drug has increased over the years and research is still ongoing into how it acts and how it exerts its characteristic effects.
