Valdoxan or Agomelatine for Depression


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.

56 thoughts on “Valdoxan or Agomelatine for Depression

  1. Great review. Are you still taking Valdoxan? I’m interested in trying it as I no longer want to take SSRI or SNRI’s because of the sexual dysfunction they cause me

    1. Thanks for the comment Lesley. While we are not on Valdoxan, we will say that the drug can be a favorable alternative for those experiencing sexual dysfunction and other sexual side effects from SSRI’s. The favorable side effect profile of Valdoxan is documented in various studies.

      Here are links to two studies (both published within the past year) that compare Valdoxan’s profile to other antidepressants.

      According to the first study, “Agomelatine may be an alternative drug for patients who complain of sexual side effects” (//

      From the other study: “Paroxetine but not agomelatine was associated with important decreased activity in dopaminergic areas such as the substantia nigra and ventral tegmental areas that could be associated with sexual performance impairment in humans after antidepressant treatment” (//

      Let us know if you have any other questions! And remember that our advice does not constitute a medical consultation; always see your doctor before making any health-related decision.

      The Health & Life Team

  2. Hi there,
    I have been trawling the web looking for insight into a possible side effect from Valdoxan of really vivid sexual dreams. I came across this site and have been reading many posts. I am 7 days into my prescription for Valdoxan 50mg, the first time I have sought help for my melancholic depression. I have entered into this journey of medication and psychologist counselling with an open mind and after spending well over ten years believing that I could push through without assistance, I have chosen to believe that life is about more than just pushing through and struggling day to day. Having an open mind has made a big difference to my attitude towards medication and I am putting my faith in my GP in his recommendation that Valdoxan will target many of my symptoms (binge eating, bouts of insomnia, feelings of hopelessness and a general lack of feeling) and I appreciate that he was honest in saying that no drug is a miracle cure and hoping for one is irresponsible. I have slept soundly for the past six nights, dropping off within 15 minutes of taking the pill and waking up clear. By no means am I bounding out of bed but really, a sound sleep and no grogginess in the morning is enough for me to not desperately crave the need to be bouncy. I have also noticed that my appetite is reducing significantly which for me is a god send because I am a textbook comfort eater and not constantly gorging to fill a hole is helping my self esteem which again is a positive. I am aware that this drug is not on the PBS (Australia) and I am paying a lot by again, an open mind that if I am prepared to pay for this medication then I am going to give it a real go. I have given up my favourite self medication of alcohol to allow my liver every chance to not be affected by Valdoxan which again has to be a positive right?
    The only thing I am really noticing is the vivid dreams that are sexual in nature.. I am not going to let this one abnormal reaction stop me though and I will be brutally honest about the content of these dreams with my psychologist, all in keeping with an open mind. I understand that no drug is the perfect fit for everyone because we are all unique human beings with intrinsically different biopsychosocial experiences but I implore people to only take others experiences as just that, their own and come at treatment with an open mind to the possibility that perhaps our attitudes need to change from demanding the perfect fit from medical professionals to observing what it is we really want to change about our symptoms and taking the little wins where we can get them.
    I wish you all every luck in your journey with utmost respect for each and every experience x

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