Last updated on July 20th, 2021 at 11:36 pm

What is Agomelatine?

Agomelatine or Valdoxan is an antidepressant with a very unique working mechanism. Most of the antidepressant drugs are selective serotonin reuptake inhibitors (SSRI). In other words, they prevent the reabsorption of serotonin into the neurons. This means more of the neurotransmitter remains available to promote the transmission of signals between nerve cells. In the process, the neurotransmitter enhances mood and emotions. The product, on the other hand, activates MT1 and MT2. Some scientists also believe that it blocks 5-HT2C serotonin receptors. The uniqueness of its mechanism of action suggests that it may be a good alternative for people who are not responding to SSRIs. There isn’t enough evidence to support its efficacy, though.

Agomelatine is approved in Europe for treating major depression. It is also used as a prescription drug in Australia. In the United States, Agomelatine is not approved by the Food and Drug Administration, but you can buy it as a dietary supplement.

Mechanism of Action

Agomelatine’s working mechanism is not fully understood, but studies suggest that it relieves depression by blocking 5-HT2C receptors on the noradrenergic and dopaminergic pathways. In doing so, it boosts the levels of norepinephrine and dopamine in the brain. This improves mood and emotions. It may also have some cognitive boosting effects.

It also acts on melatonergic M1 and M2 in a similar manner as melatonin. However, it is more powerful than melatonin and has a longer half-life, so it should theoretically have a bigger and better impact.

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Additional research is necessary to comprehensively understand how the supplement affects the brain.


Agomelatine may be beneficial in treating the following conditions:

  • Mood Disorders

Agomelatine is used in Europe to treat major depressive episodes. It is also believed to be effective for acute bipolar depression, unipolar and bipolar depression, and even alcohol dependence, as seen in this study.

Today, SSRIs are the commonly used antidepressants because they produce results without too many risks. Agomelatine may be helpful, but without sufficient clinical evidence, it’s hard to tell whether they are better than SSRIs. We also don’t know how safe they are, especially in the long-term.

  • Anxiety Disorder

Agomelatine can be useful in treating depression-related anxiety as well as generalized anxiety disorder. For depression-related anxiety, Agomelatine is more effective as an adjunctive treatment. As seen in this trial, the nootropic isn’t just showing great anti-anxiety effects, but it actually performs better than some antidepressant drugs!

In this randomized, double-blind study, patients with Generalized Anxiety Disorder were given 25 to 50mg per day for 12 weeks. The research produced some very interesting results. Scientists observed that the nootropic was very well tolerated. The adverse events experienced were no different from the placebo. They also compared the results to an antidepressant drug Escitalopram and realized the patients taking Escitalopram experienced more adverse events than the people on Agomelatine. In terms of the desired outcomes, it was concluded that Agomelatine was, at the very least, as efficacious as Escitalopram.

These studies are really promising, but they are not of the highest quality. Agomelatine may be as beneficial and safe as reported here, but it may be wiser to hold on from using it until we have bigger and more reliable clinical trials.

  • Inflammation
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Animal trials report the product can reduce inflammation by deactivating NF-kB and decreasing inflammatory cytokines IL-1beta and IL-6, which are stimulated by Lipopolysaccharides. This makes it a potential treatment for inflammation. It may also aid with metabolic conditions like obesity, insulin resistance, and diabetes.

  • Fibromyalgia

The product may be helpful in adjunctive therapies for treating neuropathic pain induced by fibromyalgia. This may be due to the drug’s effects on the serotonergic receptor 5-HT2C.

Other benefits linked to Agomelatine include:

  • Increased dopamine and norepinephrine boost motivation and mood.
  • Increased IGF-1 and Growth Hormone (GH) levels boost sleep quality, muscle strength, bone mineral density, etc.
  • Improved synaptic plasticity, which would improve cognitive functions like learning, memory, decision making, etc.

Side Effects

It has has been linked to various side effects that range from mild to severe. Some of the possible mild side effects of the drug are back pain, diarrhea, drowsiness, excessive sweating, fatigue, insomnia, migraines, nausea, anxiety, and constipation.

The drug is also associated with severe side effects like liver damage. It may increase liver enzymes and affect the performance of this vital organ. Some of the symptoms you should watch out for here are light-colored stool, dark urine, and changes in the color of your skin and eyes.

To avoid liver damage, all users should undergo a liver function test before the treatment is started. The tests should be done after every few weeks.

It may also increase the risk of suicide.


Agomelatine is usually effective at dosages of 25mg per day taken just before bedtime. The dosage can be increased to 50mg per day if 25mg is not producing the desired results.

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What if I miss a dose? Well, you should take the missed dose as soon as you remember. However, if it’s almost time for the next dosage, do not take extra tablets to make up for the missed dosage. Just take the next dose as usual.

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