Natural Remedies for Depression

Agomelatine for Depression: A Breakthrough!?

by Bill White, Licensed Counselor

How did I feel when I boned-up on agomelatine? Excited, impressed, out-of-the-loop, miffed, and cautious. Quite a combo, don’t you think?

I was really taken when I read about the efficacy of agomelatine in the treatment of depression. But I gotta’ tell ya’, I felt a little silly because I’d never heard of it.

I’m thinking much of that had to do with agomelatine not being available in the US.

What is Agomelatine?

Agomelatine (brand names: Valdoxan, Melitor, Thymanax) is an antidepressant developed by Servier Laboratories Ltd. It’s been approved for the treatment of adult major depressive disorder in Europe and Australia.

Servier sold the rights to market agomelatine in the United States to Novartis. It’s currently undergoing phase III clinical trials in the US. Novartis says the drug is scheduled for submission to the Food and Drug Administration (FDA) no earlier than 2012 (you gotta’ be kiddin’ me).

Agomelatine is known as a melatonergic agonist and a 5-HT2c antagonist. Yada, yada – bottom-line: it doesn’t work like modern antidepressants. It has no impact upon the (re)uptake of serotonin, norepinephrine, or dopamine.

The chemical structure of agomelatine is very similar to that of melatonin - catch the root name. It’s known as an analogue - a chemical compound that is structurally similar to another but differs slightly in composition.

Fewer Side Effects

Because agomelatine doesn’t increase levels of serotonin; it’s potential for gastrointestinal, sexual, and metabolic side effects is less than traditional antidepressants.

And how ’bout this? Agomelatine has no discontinuation side effects. Want to quit taking it? Do it!

Agomelatine has a positive impact upon sleep. It has no abuse potential.

Performance

It’s been reported that agomelatine has provided relief in the first week of treatment. (Frankly, I almost omitted that because I don’t want to fuel unrealistic hopes.) Agomelatine is rated very high in terms of maintenance of symptom-relief.

That said, there are unpublished randomized controlled trials that have failed to show that agomelatine is more effective than placebo.

By the way, use caution if you suffer from severe kidney and liver disease, or are a senior.

Research Findings Have Its Back

A study featuring agomelatine was published just two days ago in the online edition of The Lancet. The authors of the study are Ian B. Hickie, MD, University of Sydney, Camperdown, Australia and Naomi L. Rogers, PhD, Central Queensland University, Mackay, Australia.

According to Hickie and Rogers…

“Melatonin analogues provide a new and efficacious mechanism for producing notable phase shifts in human beings.”

From Rogers…

“Many of the traditional antidepressant treatments are effective in alleviating the mood and depressive symptoms but other symptoms, such as sleep disturbance, remain. These other symptoms can have a significant impact on quality of life, daily functioning, and also have other health impacts.”

“There is evidence that improving sleep-wake patterns and circadian rhythms improves mood symptoms, and that disturbances to the circadian and sleep-wake systems may worsen mood symptoms. In patients with depression there is evidence that sleep disturbance often occurs prior to the first onset of depressive symptoms and may also be a marker for relapse of symptoms in many patients.”

That’s All Folks!

I don’t know – if you ask me, agomelatine sounds like it’s a breakthrough medicine. But I have to wonder why Servier sold the US marketing rights to Novartis.

chipur readers in Europe and Australia may be using it right now. I wonder, is it worthy of its hype?

Feedback would really be helpful. Just use the comment box…

FYI – Here’s a link to a piece I did on melatonin back in January.

Bill White Hi! I’m Bill White, founder and producer of chipur – and a licensed counselor. Are you looking for one? The miles are irrelevant. Visit my Distance Counseling page. Join the chipur crowd on my free biweekly newsletter emailing list.

Further Reading...

  • Titurel

    Hi,
    I am from Germany. I tried Valdoxan (Agomelatonine) in 2009. I achieved an improvement in sleep quality but no further antidepressant effects. This is what most users experience (according to statements on the internet an my psychiatrist).
    So don’t expect to much from Agomelatonine!

    • http://chipur.com chipur

      Hi Titurel! Sure appreciate your visit and comment. Nothing better than personal experience and it’s great having yours on board. You know, I’m wondering if the thought is – if quality of sleep can somehow be improved, that would automatically have a positive impact upon mood. Hmmm, apparently it’s not enough in all cases. Again, thanks for you input!

      • JaniceRose

        Hi there,
        I read about Valdoxan a few years ago and being deperate for anything new, I purchased it oversees and tried it. I suffer from unipolar depression and it did squat for me. i don’t have sleep issues so if you need meds for depression and mood issues, don’t rely on this one!

      • http://chipur.com chipur

        Second such comment on Valdoxan. Just what chipur’s all about – sharing and learning (and trying to find stuff that works). Thank you!

  • http://mags1234.wordpress.com/ Mags

    I was one of the first patients prescribed this med by my psych not long after it was approved or so he said and it did nothing for me either. I stopped taking it after a few months as i couldn’t see the point of having side effects for no gain. I guess i should be grateful it didn’t send me manic as other anti depressants do. Shortly after being prescribed Ago i was diagnosed as bipolar ll and i guess this could be a reason why it didn’t work for me. 

    • http://chipur.com chipur

      Thanks for your visit and comment, Mags. Another one chalked-up for “Eeh, not so good.” And I sure agree – what sense would it make to endure side effects for no gain. Oops on the diagnosis. No doubt, antidepressants can ramp-up mania. Have you found an antidepressant regimen that works for you?

  • RobbiR

    I tried this drug too, hoping sexual response would improve.  Yeah, I slept okay, but depression came back rapidly.  I don’t know if sexual reponse was really any better ’cause who want’s to be touched when in a black and gray mood?  So now I’m back to cheerful-ish but body-dead.  Poop.

    • http://chipur.com chipur

      Thanks for your visit and comment, Robbi. Sorry things haven’t worked-out as well as you may have liked. But I gotta’ tell ya’, I got a kick out of your conclusion – “Poop!”

  • Argentalex

    Hi- I have just started Agomelatine. I have to say so far ( one week only, but still) – it’s fabulous. I am sleeping like a baby (no other antidepressant has done that- the opposite!) , I feel calm and alert during the day…
    This is a very different experience. 
    I have zero side effects, apart from slight reflux on taking the pill.
    A thought- my p doc has told me , on the quiet side, that there is quite a bit of talk amongst his colleagues who are bipolar experts, that this drug may be particularly relevant for bipolar patients, who seem much more sensitive to circadian disturbance, as part of the syndrome. I do have “soft” bipolar ie without extreme mania- so maybe that’s why I am loving it?
    All the others made me hyper and uncomfortable- and ADs in general are being questioned in treatment of bipolar(and btw, pdoc is definitely talking about adding a baby dose of a stabilizer once i adjust to this)-
    but this one , so far, works like a charm for me- and quickly.
    But early days yet, so we will see.
    Also btw- it’s not my understanding that agomelatine does not at all affect serotonin levels ( or, as I have heard claimed , dopamine and norapinaphrine, for which it’s an AGONIST- as far as I’m aware)- but that they are still working out exactly what it does re serotonin. Just for what it’s worth.

    Cheers.

    AG

    • http://chipur.com chipur

      Welcome to chipur, argentalex. A load of great information in your comment. It’s appreciated!

      Bill

  • lola

    I have to say, I have tried, lexapro, paxil, prozac, cymbalta, zoloft and now agomelatine. Out of all I liked agomelatine the best. It helped me sleep, I felt results pretty much right away but it was so gradual I felt like it wasn”t working but when I took a look back from where I was when I started to a month in there was great improvement. I was cheerful, not snappy, every little thing didnt bother me anymore. My coworkers noticed a great improvement in my behavior. I stopped taking it after 3 1/2 months b/c the taking blood every visit was getting to me. I hate needles. I have been off it now for 2 months and want to go back on. I am back to where I was before, snappy, no patience, some sleepless nights and every little thing bothers me. I get angry at stupid stuff…I feel miserable but trying to fight it. Not sure if I have major depressive or minor disorder but it sure did help me.

    • http://chipur.com chipur

      Sure appreciate your comment, Lola. I’m sure chipur readers will, as well.

      Bill

  • Mshesh

    My problem is sleep. I can not sleep a normal 7 hours sleep at night without waking up. My GP is suggesting that I start with Agomelatine.  She has since placed me on one quarter of Dormonoct and and one tablet of Trepline for two months now.  Do you think I should try Agomelatine.

    • http://chipur.com chipur

      Well, I don’t know all the details of your case history; however, agomelatine seems like a good option. If it, indeed, improves sleep/wake cycle and circadian rhythms – why not? As always, it’s your decision in conjunction with your doc…

      Bill

  • Andrea

    Hell there,
    I am from Dublin, Ireland and have been taking Valdoxen (Algomelitine) for over four months now in conjuction with Lyrica (Pregabalin) and have found the combination very helpful. I have a diagnosis of Emotionally Unstable  (Borderline) Personality Disorder, so medication is only one part of my care plan along with psychology. My main symptoms are low mood and anxiety, and since starting these drugs both symptoms have decreased in intensity ten fold. Previously I had been on Effexor and had to change due to terrible side effects, which thankfully I do not experience on these. My sleep has improved and things seem brighter. Overall I am very happy with Algomelitine. 

    • http://chipur.com chipur

      Hi Andrea!

      Sure appreciate your chipur visit and comment – I’m glad you provided such detail. And I’m pleased you shared the fact that you benefit from BOTH meds and psychotherapy.

      Please come back for a visit (or two) – and thanks for your contribution…

      Bill

  • Constantijn

    Dear Bill,

    I found your site after a search on experience reports about Agomelatine. I’m a 34 yo male, and have been suffering from clinical depression (deemed endogenous by my psychiatrist) for quite some time now. 

    I have the dubious honour of being an on-and-off guinea pig for my doctor, since in the past I haven’t been able to find any medication that improved my symptoms consistently and (as) permanently (as possible). I have tried various SSRIs (Fluoxetine, Citalopram, Sertraline) both as single therapy and in combination with Doxepine(zzzzzz). 

    I came to try out Bupropion (SR), as per my request (the doctor had no experience with it), because I wanted to try something working via a wholly different mechanism, and have been taking it ever since (at 300 mg), since it provides at least some improvement in symptoms. After some combinations with the aforementioned medications, I landed in an extremely stressful period in my life, where my doctor prescribed me (low dose) Seroquel, in order to help with sleeping, and to cope with anxiety. Surprisingly, this proved to be quite a success, and improves a lot of my anxiety related symptoms. I now take both the extended release variant (50 mg) and one 25 mg pill at bedtime.

    To finally come to Agomelatine … this was actually a suggestion by my doctor, who had been recently informed about it, and asked me if I would consider taking it, seeing as I was still complaining about depressive symptoms. With all these exotic molecules in my bloodstream, it is sometimes difficult to point out when things change, but I do remember feeling relatively alright at the time.

    At some point (couple of months ago), my doc took me off Agomelatine. As of 2 weeks ago, I’m back on it, since neither of us seemed to remember why she took me off it in the first place. 

    Long story short: in the last weeks I’ve had quite a dip (also winter-depression related), and feeling very bad. The last few days, the skies have been blue outside, and the Agomelatine seems to be working – since I now have been paying closer attention, I have noticed better sleep quality (including vivid, but not unpleasant dreams) and a pretty sudden lift in mood starting some day or two ago.

    I can’t really say that Agomelatine is a magic drug for me, but I think I can clearly notice its effects. I’m probably not a representative case, taking a (mild) psychostimulant, an atypical neuroleptic and a melatonine agonist, and I can’t judge on Agomelatine all by itself, but in general I’d say it’s worth a try if you don’t react to first- and second-line treatment, probably best as a booster medication.

    Cheers, Constantijn

    • Constantijn

      Oh the woes of clicking ‘Post’ too quickly … I should add that when my doctor took me off Agomelatine the first time, I had no discontinuation effects whatsoever (in the past, I have been able to quit relatively high doses of diazepam within a couple of days, and zolpidem within a week or 2. SSRIs, Fluoxetine excepted, have given me nastier discontinuation unpleasantnesses).

      With regard to side-effects, I have to say that I haven’t noticed anything difference between the (mild) side-effects from the other meds alone (mostly the usual seroquel stuff – Bupropion doesn’t really give me any side-effects other than a slight increase in heartrate), and the side-effects from other meds + Agomelatine.

      So, that concludes my 2 eurocents on Agomelatine so far :)

      Cheers, Constantijn

      • http://chipur.com chipur

        …and we’re all the better for your thoroughness!!!

    • http://chipur.com chipur

      Welcome aboard, Constantijn! Thank you for your detailed comment…

      Bill

  • Fred

    It would be interesting to see a study comparing agomelatine with melatonin…. Melatonin is relatively inexpensive and I believe doesnt hurt the liver/kidneys.

    • http://chipur.com chipur

      Thanks, Fred. Perhaps someone will chime in with something…

      Bill

  • Janefrench

    HI, I’m bi polar, high depression. after 6 years on antidepressants,mood enhancers and sleep enhancers I am not quite a moron, but awfully close to. so this week I started on valdoxen. it has disrupted my sleep initially but improving each day. I had my first dream in 6 years last night – a dream of rebuilding a home from building blocks, and finding old friends and work colleagues in each box.
    I have now discarded the antidepressants, under instructions of my psychiatrist. I am told the circadian rhythm concept takes only days to establish. I am also told the last thing you should give a bi polar patient is an anti depressant. so if the valdoxen fixes the sleep and the antidepressants are gone, it’s just a few more weeks of eliminating mood enhancers, sleep enhancers, and I should be back to only valdoxen.

    I already have had windows of moments of the same light hearted energetic joy I used to enjoy, and it’s like seeing yourself in the past.

    • vv2808

      Hi Janefrench,

      I am also bipolar II and have just been given valdoxen to try for 3 weeks, after trialing many antidepressants, then tegratol, then lamotragine. I had an allergic reaction to both of these, and was told the next logical step is lithiuim, which I am loathe to try, so my pdoc suggested valdoxen as an alternative. I am keen to ask how you have gone for the past 2 weeks on this?

  • Ashleyv08

    I was in a clinical study for Agomelatine under Novartis. I have had depression for years and tried a few different medicines for it including Lexapro and Zoloft. Agomelatine has been the best medicine for it by far! At the beginning of the study I am certain I was on the placebo as there was no change in my depression. But when I went to open label and was on the actual medicine I saw a significant change. I have also had trouble with sleep and tried Ambien for about 2 nights… I was practically in a coma on Ambien and as mother of two that is obviously not a good thing! While on Agomelatine I was able to fall asleep easily, if i needed to wake up to mommy my kids in the middle of the night I was able to do so coherently, and most important of all i was able to go back to sleep afterward and feel fully rested in the morning. Anyone with depression, sleep disorders and kids knows how vastly important this is!!! I have been trying to keep an eye on the production of Agomelatine in the United States since the conclusion of the study because I would very much like the have it as my daily depression medicine. I liked the Agomelatine because if made me feel like myself, not the “me” on antidepressants, or “me” without medicine, but the me I want to be… interactive with my family, fun, outgoing, and able to handle the day to day without it feeling like life is just a crushing weight. I hope this has given some insight for anyone doing any kind of research on the drug. It may not work for everyone and it is not a fix-all but it improved my life while i was taking it… enough that i was propelled to search its production progress and comment on here. :-)

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