Agomelatine: characteristics and side effects of this antidepressant

Today there are many pharmacological tools to treat people suffering from a depressive disorder. Among the 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 the circadian rhythms of the dream.

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 disorders other than depression.

• Related article: "Types of antidepressants: characteristics and effects"

Agomelatine: description and clinical uses

Agomelatine is an atypical antidepressant drug used to treat 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. S considers this drug to be an analogue of melatonin.

Clinical studies conducted with agomelatine indicate that it is a valid drug for treating 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 surprisingly, and as we will see below, its particular mechanism of action, through which is able to modulate circadian rhythms, makes it especially unique as far as its pharmacological profile is concerned.

• You may be interested in: "Major Depression: Symptoms, Causes, and Treatment"

Mechanism of action

The mechanism of action of the melatonin it 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 has no affinity for adrenergic, histamine, cholinergic, dopaminergic, and serotonergic receptors, as occurs 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 sleep phase syndrome. delayed, a disorder that affects the quality and type of sleep, the rhythm of body temperature, the hormonal rhythm, among other functions biological.

On the other hand, agomelatine increases the release of the neurotransmitters dopamine and norepinephrine, especially in regions of the cerebral frontal 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-dopamine-disinhibiting antidepressant. In addition, the antagonistic effect on the 5-HT2b receptor is a property that it shares with various atypical antipsychotic drugs (eg. e.g. aripiprazole), which are also used as antidepressants).

At present, various investigations are focused on studying the usefulness of drugs that exert antagonism on the 5-HT2b receptor to reduce headache (in migraines and headaches, 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 it produces fewer side effects and adverse effects than the vast majority of antidepressant drugs. Agomelatine does not alter attention span or memory. In addition, in depressed 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. In addition, from the first week of treatment with agomelatine, patients report an increase in the onset time and in the quality of sleep, without causing changes in mobility (p. e.g. daytime clumsiness).

However, the use of agomelatine is not exempt from possible side effects. More serious, but also rare, adverse reactions include migraine, restless leg syndrome, eczema, excessive sweating, agitation, irritability or even aggressive or self-injurious behaviors. And among the most common, we can highlight the following:

• Headache.
• Dizziness and drowsiness.
• Difficulty 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. Patients most often experience episodes of depression 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 noted its effects after 2 weeks, with a notable reduction in the symptoms associated with the syndrome (mood changes, difficulties sleeping and others).

In said study, agomelatine showed excellent tolerability at a dose of 25 mg, without the significant side effects typical of other antidepressant drugs. About a third of the patients noted mild drowsiness after taking the drug; 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. Various investigations have shown 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 that included nearly 2,000 patients with major depressive disorder, more than 900 of whom had 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), in addition to a placebo.

The results of the analysis concluded that agomelatine significantly reduces the symptoms of anxiety, already from the second week of treatment, and in a more effective way than the rest of 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 where those with comorbid anxiety, and also in people with circadian rhythm disorders, as discussed above. For all these reasons, clinical interest in the drug has increased over the years, and how it works and how it exerts its characteristic effects is still being investigated.

Bibliographic references:

• 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.