Agomelatine is a melatonergic antidepressant for people who are diagnosed with clinical depression and need a strong drug to relieve them from their depression symptoms.

Many people these days are suffering from depression and are prescribed different medications. One of them in particular is Agomelatine, marketed under the trade name of Valdoxan, which is quite effective, has limited side effects, unlike other similar antidepressants, while providing similar therapeutic benefits. It can particularly be effective in sleep regulation.

People who suffer from depression can often experience disturbances of their ‘body clock’, which can be noticed by changes in daily sleep and appetite patterns, among other things.


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What is Agomelatine all about?

Agomelatine was developed by a French pharmaceutical company called Servier  and works on the receptors of the brain which release the hormones serotonin, responsible for inducing sleep, and melatonin, responsible for maintaining sleep/wake timings and schedules for the body. It has shown to change the circadian rhythms in the brain of individuals in order to reduce stress levels. The brain releases serotonin and melatonin which help regulate sleep and then get reabsorbed. Valdoxan interrupts the process by stopping these hormones from being reabsorbed causing the brain to release more of these resulting in a calmer and stress free person.

How does Agomelatine affect people?

Even though agomelatine was developed and introduced in the recent years, it has made a reputation for itself to be as effective as the other antidepressants in the market. There were medicinal trials conducted by the pharmaceutical company and the results on the participants were favorable. This was because their depression percentage was reduced to half by taking Valdoxan according to the reports.

Even though all antidepressant trials are conducted with the same kind of results and effectiveness on the participants, it is important to note that everybody’s response rate is different. Therefore, if one doesn’t find a drug working for them, then an alternative can be taken. Agomelatine takes about 10-15 days to show an effect on an individual, so a little patience is required to see the desired result.

What kind of disorders does Agomelatine treat?

Agomelatine is used to treat all major anxiety disorders that lead to clinical depression.

A little bit of anxiety is normal for a person but if that anxiety lingers on and develops and grows into something bigger and worse, then there is a problem. If there is an underlying problem, that would need to be addressed and diagnosed by a doctor. These anxiety disorders vary by type, intensity and individuals are treated accordingly. Anxiety disorders affect a person’s daily life in every way and can cause major issues in the long run if not treated correctly. People who suffer from depression can often experience disturbances of their ‘body clock’, which can be noticed by changes in daily sleep and appetite patterns, among other things.

Following are the 5 major types of anxiety disorders that Agomelatine can help with.

Major Depressive Disorder

This is the most commonly known disorder out there and is famously known as “depression”. Depression is if someone is suffering from extreme sadness for more than 2 weeks and has lost interest in everything they previously used to enjoy and do not enjoy life anymore. Agomelatine can relieve symptoms of depression in the first week of usage. Symptoms such as loss of appetite, bad mood and lack of sleep were improved significantly.

General Anxiety Disorder (GAD)

GAD is a mental disorder in which someone is excessively worried about something, in layman’s terms, “paranoid”. People who suffer from this get worried and always assume disastrous outcome for any given situation. Agomelatine works by affecting 2 of the neurotransmitters in the brain called serotonin and melatonin. This helps a person suffering from the disorder and make them relaxed.

Social Anxiety Disorder

This makes people extremely nervous in any social encounter or gathering where there are many people. It is hard for them to interact with people and usually get a fast heartbeat and start sweating or stuttering (in extreme cases). Agomelatine is a serotonin and melatonin inhibitor that helps people who get stressed out become calm and relieved.

Bipolar Disorder

This is also known as manic depression and as the name suggests, causes a person to have opposite feelings and behaviours. A person may be highly energetic and happy one day and can feel extremely depressed and have no energy or desire to do anything the other day. These periods can last from days to months. Agomelatine helps bipolar patients by affecting the hormone serotonin in the brain circuit. Serotonin helps in regulating the mood and so increasing the levels of it would help relieve the symptoms for the patient.

Obsessive Compulsive Disorder

Also known as OCD, it is a mental disorder that affects people that have strong and repetitive urges to activities that affect their daily lives. For e.g., people get obsessed with cleanliness and start washing their hands repetitively every 5 minutes. Or if they think the door isn’t shut correctly, they open and shut it over and over. Agomelatine works with melatonin and serotonin and blocks their reabsorption after being released and thus makes a person relaxed, less jittery and improve their compulsive urges to perform an activity repetitively.

Important notes:

  • It is highly important to know that agomelatine is not available without a doctor’s prescription so will not find this drug over the counter. Ask your doctor if agomelatine is right for you.
  • This drug does not have any effect on the sexual activities of an individual.
  • Should not be used if someone has liver problems. If it is prescribed, then a liver check up is a must before proceeding to take If the dosage of the drug is increased, then there should be a liver check up test performed again.
  • The general dosage is 25mg taken at bedtime every night. If there is no sign of improvement or change of behavior or moods in the next 2 weeks, then the dosage can be increased to 50mg (if the doctor deems it to be).

Melatonergic Antidepressant

This is a drug which was created to control the melatonin functions in the brain. Melatonin controls the sleep cycles known as the circadian rhythm. Since sleep affects the energy levels and mood of the people, by having optimum levels of melatonin in the body, patients of depression have known to reduce their symptoms and get treated effectively. Agomelatine is known to be the first meltonergic drug.

History

It was first introduced as agomelatine by the Pharmaceutical Company Servier in 2006 and was sold under the names Thymanax and Valdoxan in the European market to treat people suffering from depression and other anxiety disorders. In Australia, it was approved for marketing in late 2010.

 Mechanism of Action

A synthesized melatonin analog, agomelatine was originally under testing for its chronobiotic tendencies. During initial testing, researchers observed that it was also having a certain effect on the serotonergic receptors. That was when research began in earnest into exploring its effects as an antidepressant. Further research showed that agomelatine acted as antagonist at serotonin receptor 5HT2C and an agonist at the melatonergic receptors (MT1, MT2).

When it comes to major depression and its pathophysiology, a number of hypotheses have been put forth, prime among which is Phase-shift. This particular hypothesis proposes that depression may be caused by a phase delay in the body’s internal clock (circadian rhythm). When the melatonergic receptors are stimulated as a result of use of agomelatine in the suprachiasmatic nucleus, the circadian rhythm is restored to optimal state. That’s why this synthetic analog is sometimes referred to as a “rhythm stabilizing antidepressant”.

Next we have the analog’s secondary function: boosting dopamine and norepinephrine levels by binding selectively to the serotonin receptor (5HT2C). This function serves to suppress and treat depression as well. Note that a melatonerergic drug such as Agomelatine does not affect the histamine, adrenergic, and cholinergic receptors.

Contraindications

It is known to be contraindicated with the people who have kidney and liver problems. Doctors have to first run tests for people who have any liver or kidney diseases prior to prescribing this drug.

It is advisable to be having blood tests prior to and periodically during the use of this drug to check liver and kidney function is adequate.

How to Take

It should be taken only as the doctor has prescribed (not exceeding or changing the dosage without consultation) and only one tablet taken in the evening at bedtime with a glass of water. If there are not any results during the first week, then consult your doctor to increase the dosage, the recommended maximum dosage is 50 mg daily.

Side Effects

Common side effects associated with the use of agomelatine are generally limited as it is usually well tolerated, and seem less severe than SSRIs and SNRIs. It also appears to avoid sexual dysfunction and gaining of body weight. However, if they last long or become severe, immediately consult your doctor, as they may be related to general health or any other treatments.

Common side effects in people who take this drug are:

  • Hyperhidrosis (excess sweating)
  • Abdominal pain
  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Back pain
  • Fatigue
  • Headache
  • Dizziness
  • Somnolence (sleepiness)
  • Insomnia
  • Migraine
  • Anxiety
  • Liver failure (in rare cases when liver problems are not documented or tested)

Seek immediate advice from your medical practioner should you notice things such as dark urine, yellow skin or eyes (jaundice), light coloured faeces, pain in your upper right abdomen or new-onset and unexplained fatigue, as these could be symptoms of potential liver problems .

Overdose, Tolerance and Withdrawal Effects

Agomelatine is fairly safe when it comes to over dosage. It does not seem to cause direct fatalities by overdose but can increase the side effects and related symptoms. In case of any overdose, go to the emergency department of a hospital along with the medicine container. No known withdrawal symptoms have been reported for this drug.

Women and Children

It is not recommended for pregnant or breastfeeding women to take Valdoxan. Children below the age of 18 are not prescribed nor recommended any melatonergic drug such as Agomelatine.

Dependency

There are no cases of dependency and abuse cases for this drug, therefore, it does not cause any serious problems if tapered.

Conclusion

A melatonergic drug such as Agomelatine has shown the efficacy in relieving the symptoms of depression in people and is the only antidepressant that acts on melatonin.
The potential for liver reaction exists and should be dealt with immediately you notice any signs this may be occurring, as explained above.
If you are starting on Valdoxan, it is recommended to consult a reliable doctor before starting the medicine, to discuss your health and other medicines, supplements or herbal products that you may be using throughout the treatment period.