Agomelatine: characteristics and side effects of this antidepressant

A review of the characteristics of agomelatine, an Antidepressant that affects melatonin.

Nowadays there are a multitude of pharmacological tools to treat people suffering from a depressive disorder. Among the antidepressant drugs, 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 the circadian rhythms of sleep.

In this article we explain what agomelatine isIn this article we explain what agomelatine is, its clinical uses and mechanism of action, its main side effects and its uses in disorders other than depression.

Agomelatine: description and clinical uses

Agomelatine is an atypical antidepressant drug used for the treatment of major depressive disorder. This drug 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 a melatonin analog.

Clinical studies conducted with agomelatine indicate that it is a valid drug for treating depressive episodes in adults. Its antidepressant effect is more potent in severe depression, and it has 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.

Moreover, a 2018 meta-analysis comparing 21 antidepressant drugs concluded that agomelatine was one of the most tolerable and effective drugs. Not surprisingly, and as we will see below, its particular mechanism of action, through which it is capable of modulating circadian rhythms, is is able to modulate circadian rhythms, makes it particularlymakes it particularly unique as far as its pharmacological profile is concerned.

Mechanism of action.

The mechanism of action of melatonin is quite peculiar within the group of antidepressants. This drug exerts its therapeutic effects by acting as an agonist of the melatonin receptors (MT1 and MT2) and (MT1 and MT2) and as an antagonist of serotonin receptors (5-HT2c and 5-HT2b).

Studies indicate that it has no effect on monoamine absorption and has no affinity for adrenergic, histaminic, cholinergic, dopaminergic and serotoninergic receptors, as is the case with other antidepressants.

A particular feature of agomelatine is its ability to modulate or resynchronize circadian rhythms. In studies with animal models, it has been shown to have positive effects in cases where there is a delayed sleep phase syndrome, a disorder that affects the quality and type of sleep, body temperature rhythm, hormonal rhythm, among other biological functions.

On the other hand, agomelatine increases the release of the neurotransmitters dopamine and noradrenalinespecially in regions of the cerebral frontal cortex, due to its action as an antagonist of serotoninergic receptors (specifically, 5-HT2c). This is why this drug is sometimes classified as a noradrenaline and dopamine disinhibiting antidepressant. In addition, the antagonistic effect on the 5-HT2b receptor is a property it shares with several atypical antipsychotic drugs (e.g., 5-HT2c, 5-HT2b, 5-HT2b, 5-HT2b, 5-HT2b). (e.g. aripiprazole), which are also used as antidepressants).

Currently, several investigations are focused on studying the usefulness of drugs that exert antagonism on the 5-HT2b receptor to reduce headache pain (in migraines and migraine headaches, for example). Therefore, it should be noted that this antagonistic effect of agomelatine has been shown to be useful for its depressant effectiveness, but also for its ability to reduce the adverse effects of the drug.

Side effects

One of the advantages of agomelatine is that it it produces fewer side and adverse effects than the vast majority of antidepressant drugs.. Agomelatine does not alter attentional capacity or memory. Furthermore, in depressive patients its use increases slow wave sleep without modifying the amount of REM (rapid eye movement) sleep 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 sleep onset time and sleep quality, without producing alterations in mobility (e.g. daytime clumsiness).

However, the use of agomelatine is not without possible side effects. More serious, but also infrequent, adverse reactions include migraine, restless legs syndrome, eczema, excessive sweating, agitation, irritability or even aggressive or self-injurious behavior. And among the most common, we can highlight the following:

• Headache.
• Dizziness and drowsiness.
• Difficulties in falling asleep.
• Diarrhea or constipation.
• Abdominal or back pain.
• anxiety
• Nightmares or strange dreams.
• vomiting
• Weight gain.

Effects of agomelatine in seasonal affective disorder.

Seasonal affective disorder is a subtype of major depressive or bipolar disorder characterized by recurrent affective episodes in the same season of the year. characterized by recurrent affective episodes in the same season of the year. Patients most often suffer from depressive episodes during autumn or winter, which are followed by remission or hypomanic episodes. These individuals show a delay in the onset of depression.

As mentioned above, research suggests that agomelatine may 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 swings, sleeping difficulties and others).

In that study, agomelatine showed excellent tolerability in doses of 25 mgThe results showed no significant side effects typical of other antidepressant drugs. About one-third of the patients noted mild drowsiness after ingestion of the drug; however, only one patient experienced subjective impairment (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 various studies that have been carried out in recent years. In several investigations, it has been proved that the anxiolytic efficacy of agomelatine is more potent in depressed patients suffering from severe anxiety symptoms..

In a meta-analysis of six multicenter studies involving almost 2000 patients with major depressive disorder, more than 900 of whom 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 noradrenaline reuptake inhibitor (venlafaxine), in addition to a placebo.

The results of the analysis concluded that agomelatine significantly reduced anxiety symptoms as early as the second week of treatment, and more effectively than the other antidepressants. Moreover, the positive effects were even more pronounced in people with depression who also suffered from a high degree of anxiety.

In short, agomelatine has not only been shown to be an effective drug against depressive symptoms, but also in cases where there is comorbid anxiety, and also in people with circadian rhythm disorders, as mentioned above. Por todo esto, el interés clínica por el fármaco ha aumentado con los años y todavía se sigue investigando cómo actúa y de qué forma ejerce esos efectos tan característicos.

Referencias bibliográficas:

• De Bodinat, C., Guardiola-Lemaitre, B., Mocaër, E., Renard, P., Muñoz, C., & Millan, M. J. (2010). Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nature reviews Drug discovery, 9(8), 628.
• Pjrek, E., Winkler, D., Konstantinidis, A., Willeit, M., Praschak-Rieder, N., & Kasper, S. (2007). Agomelatine in the treatment of seasonal affective disorder. Psychopharmacology, 190(4), 575-579.
• De Berardis, D., Marini, S., Fornaro, M., Srinivasan, V., Iasevoli, F., Tomasetti, C., Valchera, A., Perna, G., Quera-Salva, M.A., Martinotti, G. & Di Giannantonio, M. (2013). The melatonergic system in mood and anxiety disorders and the role of agomelatine: implications for clinical practice. International journal of molecular sciences, 14(6), 12458-12483.