Valdoxan or Agomelatine

About 40-50% of people taking the current antidepressants, or the SSRIs, stop treatment shortly after starting. This is because that class of medications has certain significant side effects, like nauseua and sexual dysfunction.

Valdoxan, generic agomelatine, seems to be an effective antidepressant that doesn’t have those problems.

Valdoxan is a synthetic analogue to melatonin, a natural substance your body has that plays a role in sleep regulation. Chemically, it serves to activate the melatonin 1 and 2 receptors, while also acting as an antagonist to 5-Ht2.  This latter activity may serve to promote release or norepinephrine and dopamine.

It’s important to note that Valdoxan has significantly different chemical action than the selective serotonin reuptake inhibitors (SSRIs).

Possible Advantages

Valdoxan may not have the same rate or degree or type of side effects as traditional antidepressants. It may not cause nausea, sexual dysfunction and other common side effects.

It may start working faster, with some efficacy observed at just two weeks, not the four typically needed for antidepressants.

Both these elements may mean that people will be less likely to want to stop taking it and could start expereincing benefit at an earlier time.  In some studies, only 15% stopped use of Valdoxan, which is much less than the rate traditional antidepressants have.

This may mean a very significant advantage over traditional treatment.


Several studies of Valdoxan have not shown significant advantage over placebo.

Because Valdoxan is heavily metabolized by the liver, people with some form of liver damage may experience toxicity.  One study showed that some degree of liver impairment could lead to a 50-fold increase in drug concentration.

Valdoxan may, like the SSRIs, increase risk of suicidal ideation.


The number one question people have about any medication is, how well does it work?  It appears that there have been 7 major studies to date which have analyzed the efficacy of Valdoxan for treating depression, and there are others going on to see if it works for generalized anxiety disorder and other conditions.

Positive studies

One study showed that Valdoxan was significantly more effective as a treatment for depression than Prozac.

A study of 711 people treated for depression showed that it was significantly better than placebo and had effect starting at 2 weeks.  Additionally, that study showed that severely depressed people were more likely to respond to Valdoxan than to Paxil.

Another study of 238 people showed a roughly 55% response rate versus 35% response to placebo.

Negative Studies

Several have also shown little or no benefit over placebo.  An unpublished 6 week long study of 414 patients showed that Valdoxan had a response in 53% of those taking it compared to 47% who responded to placebo.  That same study showed that Prozac did have a significant response.

And another 6 week long study of 607 patients showed that neither Valdoxan or Prozac had benefit for treating depression over placebo.

What it means

Valdoxan is not free from the problems that typical antidepressants have, that sometimes they don’t seem to work much better than placebo.  The studies seem to indicate that it is about as effective as traditional antidepressants while having significantly less side effects and possibly faster onset of action.

These advantages may make it extremely popular. That said, the concerns around its metabolism have yet to fully be addressed, and there may be other issues that time will reveal.


In 2018, a study confirmed it to be an effective combination of an antidepressant, with minimal side effects.

According to readers who commented on this article, it seems a good deal of them derived benefits by treating their depression, while others who didn’t attain much in the way of treatment for their depression but didn’t experience side effects either, but despite it’s renown for being tolerable, it seems, in the real world, side effects typical of other anti-depressants are not uncommon.

Some of the readers say it has treated their depression and anxiety while other comments point to side effects and in few cases rather nasty ones. The following side effects have been experienced by some of the readers of this article. Of course, these will vary from person to person and how extreme they are.

  • irritable
  • hair loss
  • suicidal thoughts
  • dreams


There is a lot of controversy around antidepressants. Antidepressants – the Pros and Cons looks at both sides of the story.

Treatment Resistant Depression

Sometimes depression does not respond to treatment.  Here we present 10 ideas for Treating Treatment Resistant Depression.

Dealing with Anxiety

Depression and anxiety tend to come together.  See The Top 25 Anxiety Tips for ideas on how to deal with anxiety.



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