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Agomelatine: Melatonin as an AD?


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http://news.health.com/2011/05/18/new-antidepressant-body-clock/

 

In an article published this week in the Lancet, Dr. Hickie suggests that melatonin-based drugs could prove to be safer and more effective treatments for depression than the antidepressants currently in use. In particular, he and his coauthor highlight the potential of a new drug called agomelatine, a synthetic version of melatonin that also increases concentrations of dopamine and norepinephrine in the brain.

Off Lexapro since 3rd November 2011.

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Sounds great. Another drug that messes with the natural neurotransmitter balance...I wonder how they come to the conclusion that it may be safer.

End of 2008: Remeron 15mg for around 2 months. Unorthodox taper, no problems.
End of August 2009: Lexapro 10mg for only 4 days. Panic attack after 3 pills. Severe gastro problems in the morning for 3 days after last pill. 2 weeks later strong w/d symptoms set in.

Acute WD lasted around 3.5 years. I am feeling much better today, 5.5 years out, but still have some symptoms left.

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http://news.health.com/2011/05/18/new-antidepressant-body-clock/

 

In an article published this week in the Lancet, Dr. Hickie suggests that melatonin-based drugs could prove to be safer and more effective treatments for depression than the antidepressants currently in use. In particular, he and his coauthor highlight the potential of a new drug called agomelatine, a synthetic version of melatonin that also increases concentrations of dopamine and norepinephrine in the brain.

Hmm, in an attempt to alleviate the horrific insomnia I encountered while tapering off my med cocktail, I took melatonin. I experienced suicidal ideation.

 

I tried it a 2nd time after being off of meds and while fortunately, I didn't experience suicidal ideation, I experienced depression that was not related anything happening in my life.

 

All meds that have different chemical actions from the previous ones are supposed to be the latest and greatest. Didn't work too well with the SSRIS and the atypical antipsychotics.

 

Sorry for being so cynical.

 

CS

Drug cocktail 1995 - 2010
Started taper of Adderall, Wellbutrin XL, Remeron, and Doxepin in 2006
Finished taper on June 10, 2010

Temazepam on a PRN basis approximately twice a month - 2014 to 2016

Beginning in 2017 - Consumption increased to about two times per week

April 2017 - Increased to taking it full time for insomnia

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I agree, the jury is still out on the safety of this new drug.

 

By the way agomelatine is not a synthetic melatonin. This is what it does, according to wikipedia:

 

https://secure.wikimedia.org/wikipedia/en/wiki/Agomelatine

Agomelatine is a melatonergic agonist (MT1 and MT2 receptors) and 5-HT2C antagonist.

Calling it a synthetic melatonin is like calling Prozac a synthetic serotonin. My alarm bells ring when I see a medical researcher describing a drug with a euphemism that makes it more attractive to the consumer.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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I tried taking melatonin for sleep (a very small dose) about a year ago. I can't remember exactly why... but it didn't work for me. I seem to remember feeling very wide awake and anxious.

 

 

Charter Member 2011

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It's one of those things where if you take too much, you get a paradoxical effect.

 

On the other hand, some people just don't do well with taking melatonin.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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Adding in my two cents, melatonin was another thing I tried that ended up giving me anxiety. It did nothing to help me sleep. I had one night when I took melatonin and would sleep in 15 minute increments, waking up terrified and exhausted.

1989 to 2008: Prozac then Paxil then Celexa.

Numerous attempts to quit.

Then I got off the SSRI poop-out merry-go-round.

11-12 week taper.

 

Muddy water, let stand, becomes clear

If you're going through hell, keep walking

The only way out is through

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  • 3 weeks later...
Barbarannamated

I've tried melatonin for sleep, also. I don't know that it helped any. Scary to hear of your reactions.

I believe serotonin is precursor to melatonin. Hadn't heard of this new drug.

Pristiq tapered over 8 months ending Spring 2011 after 18 years of polydrugging that began w/Zoloft for fatigue/general malaise (not mood). CURRENT: 1mg Klonopin qhs (SSRI bruxism), 75mg trazodone qhs, various hormonesLitigation for 11 years for Work-related injury, settled 2004. Involuntary medical retirement in 2001 (age 39). 2012 - brain MRI showing diffuse, chronic cerebrovascular damage/demyelination possibly vasculitis/cerebritis. Dx w/autoimmune polyendocrine failure.<p>2013 - Dx w/CNS Sjogren's Lupus (FANA antibodies first appeared in 1997 but missed by doc).

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This new drug is Valdoxan.

 

It isn't melatonin per se, it acts on the melatonin receptor. It's probably going to be approved in the US soon.

 

Coincidentally, I just talked to a knowledgeable doctor about Valdoxan. He said it's an agonist, which means it will have dependency and withdrawal issues.

 

I shudder to see downregulation of and damage to melatonin receptors. That withdrawal is going to be very, very hard.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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What I've read about this says it does not have withdrawal problems:

 

With some antidepressants, if you stop taking them suddenly, side effects – called discontinuation symptoms – can happen.

 

Agomelatine does not cause this problem. When you and your doctor agree that it’s time for your treatment to finish, you can just stop taking the tablets.

http://whatyoushouldknow.depression-alliance.co.uk/antidepressants/agomelathine-2/

 

Of course, doesnt mean its true.

 

Btw Alto, could you explain what "agonist" and "antagonist" mean in drug terms? It's always confused me.

Off Lexapro since 3rd November 2011.

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An agonist pushes the spout to increase production of a neurohormone.

 

An antagonist blocks the spout, often paradoxically increasing production because other spouts take over.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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Barbarannamated

Did you see the last line in that link? something like this:

"This is not a sign you are getting hooked on them....ADs do not cause drug dependence."

I beg to differ w that statement! Dependence and addiction ('hooked') are not the same. Because one doesn't crave the next dose or need increasing amounts does not equate to lack of physiological dependence.

Pristiq tapered over 8 months ending Spring 2011 after 18 years of polydrugging that began w/Zoloft for fatigue/general malaise (not mood). CURRENT: 1mg Klonopin qhs (SSRI bruxism), 75mg trazodone qhs, various hormonesLitigation for 11 years for Work-related injury, settled 2004. Involuntary medical retirement in 2001 (age 39). 2012 - brain MRI showing diffuse, chronic cerebrovascular damage/demyelination possibly vasculitis/cerebritis. Dx w/autoimmune polyendocrine failure.<p>2013 - Dx w/CNS Sjogren's Lupus (FANA antibodies first appeared in 1997 but missed by doc).

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As I understand it, all agonists cause dependence, and reuptake inhibitors act as agonists, causing downregulation of receptors.

 

However, I know from personal experience drugs that are not either agonists or reuptake inhibitors have withdrawal issues. Estrogen, for example.

 

Absolutely do not believe any early research or other claims about a psychiatric drug not having withdrawal problems! So far, that's always been proven to be untrue, once enough people take it long enough.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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  • 1 month later...

A few reports of Agomelatine (looks like you were right, Alto).

 

from: http://www.socialanxietysupport.com/forum/f30/agomelatine-brand-name-valdoxan-113208/index2.html

 

So it's been almost one week, and I'm so depressed. I'm not so anxious, instead I'm debilitatingly depressed, I can't study/think/do my work, I feel hopeless, etc. I don't really want to cook or eat, either. Which is so unlike me, I love food. I'm not sleeping any better, either. But I do feel less paranoid. I will keep going for a month, if my life doesn't fall apart first.

Ok I'm coming off of this now. It was only three weeks but made me waaay too depressed. I couldn't function at all.

I haven't taken agomelatine for two nights, and I'm feeling a bit better than I did before I took the agomelatine. In three weeks, could it have downregulated some 5HT2-c receptors?

 

I can understand why I wouldn't feel good on the ago because it hits those receptors mildly.

 

I don't know the first thing about melatonin systems (and I'm kind ADD right now so anything more than bullet points will make my eyes glaze) so I can't say if it's melatonergic.

 

If this is the case, feeling this well is enough for me to go back on ago periodically in spite of the intense depression, in order to reap the benefits I'm feeling now.

and: http://www.socialanxietysupport.com/forum/f146/lyrica-pregabalin-84116/

 

This is the chick that blogged about agomelatine. Agomelatine was a newish drug when i started it. I had no success on it and when i dropped it cold turkey i eventually ended up hospitalised. One of the reasons my psych thought it would be good for me was that i suffer from anxiety i think i can say it really didn't help me with that at all. My diagnosis has since been changed, although anxiety still remains a problem. Although i blogged about it my experiences may not be that useful to many. Since my change in diagnosis it has been stated that i am very sensitive to anti depressants and that they have a huge impact on my mental health therefore i am never to be prescribed them again. I have just been prescribed Lyrica for my anxiety and aggitation hopefully it will work and i will have few side effects.

Off Lexapro since 3rd November 2011.

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Agomelatine is being pushed in Dubai:

 

http://www.middleeastevents.com/site/pres_dtls.asp?pid=14460

 

Keynote speaker, Prof. Siegfried Kasper from Vienna University presented data on major international studies highlighting the enhanced treatment properties of the new antidepressant known as Agomelatine over traditional antidepressants.

 

Notable enhancements include greater patient improvement on depressed mood from the first week of treatment and favourable tolerability. Weight gain and sexual dysfunction -notorious side effects of traditional antidepressants- are not associated with Agomelatine.

 

Prof. Kasper explained: “From the very first week of treatment, Agomelatine provided significant clinical improvement as reported by both doctors and patients. More precisely, patients themselves reported feeling better, with improved daytime functioning, as early as the first week of treatment.”

 

Agomelatine has been registered and available in Europe since 2009, and has been registered by the ministry of health in Kuwait, Bahrain, Oman, Qatar and the UAE. It is now available for the treatment of adult patients suffering from major depressive disorder in these same countries.

Off Lexapro since 3rd November 2011.

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  • 3 months later...
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Looks like the studies showing agomelatine might be a good antidepressant were -- yep -- jimmied to give glowing results. See http://1boringoldman.com/index.php/2012/02/13/a-bad-sign/

 

Recently, agomelatine failed its most recent Phase III clinical trial for FDA approval for distribution in the US.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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Looks like the studies showing agomelatine might be a good antidepressant were -- yep -- jimmied to give glowing results. See http://1boringoldman.com/index.php/2012/02/13/a-bad-sign/

 

Recently, agomelatine failed its most recent Phase III clinical trial for FDA approval for distribution in the US.

 

I am absolutely stunned that this could happen :rolleyes:

 

CS

Drug cocktail 1995 - 2010
Started taper of Adderall, Wellbutrin XL, Remeron, and Doxepin in 2006
Finished taper on June 10, 2010

Temazepam on a PRN basis approximately twice a month - 2014 to 2016

Beginning in 2017 - Consumption increased to about two times per week

April 2017 - Increased to taking it full time for insomnia

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I'm certainly skeptical of anything man-made at this point. I'm reading a book called The Last Well Person by Nortin T. Hadler, M.D. and he holds that even taking calcium and Vitamin D does no good for osteoporosis because each person has their own unique set-point for the calcium balance in the bloodstream. Once that balance is reached, the body dumps the excess. According to Jim Mercola, M.D., the calcium often gets dumped where it causes trouble: http://articles.mercola.com/sites/articles/archive/2012/01/30/calcium-supplement-on-heart-attack.aspx?e_cid=20120130_DNL_art_1

 

If something as innocent seeming as a caclium supplement can hurt us, I'm really, really skeptical of tampering with melatonin.

 

Melatonin sometimes helps me sleep, sometimes not. No adverse reactions so far, but I think I'm very close to having my neural pathways made straight again. I've actually gotten tired and taken naps in the afternoon recently. (Keep in mind that I was on ADs for only sixteen months.)

Psychotropic drug history: Pristiq 50 mg. (mid-September 2010 through February 2011), Remeron (mid-September 2010 through January 2011), Lexapro 10 mg. (mid-February 2011 through mid-December 2011), Lorazepam (Ativan) 1 mg. as needed mid-September 2010 through early March 2012

"Never attribute to malice that which is adequately explained by stupidity." -Hanlon's Razor


Introduction: http://survivingantidepressants.org/index.php?/topic/1588-introducing-jemima/

 

Success Story: http://survivingantidepressants.org/index.php?/topic/6263-success-jemima-survives-lexapro-and-dr-dickhead-too/

Please note that I am not a medical professional and my advice is based on personal experience, reading, and anecdotal information posted by other sufferers.

 

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  • 1 year later...
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1boringoldman.com hammers the last nails into the coffin of agomelatine as an antidepressant:

http://1boringoldman.com/index.php/2013/09/04/a-breath-of-fresh-air-3/

 

http://1boringoldman.com/index.php/2013/09/05/the-days-of-faux-blockbusters/


From http://bjp.rcpsych.org/content/203/3/179.short
 

Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials

Markus Koesters,
Giuseppe Guaiana,
Andrea Cipriani,
Thomas Becker and
Corrado Barbui

Abstract

Background

Agomelatine is a novel antidepressant drug with narrative, non-systematic reviews making claims of efficacy.

Aims

The present study systematically reviewed published and unpublished evidence of the acute and long-term efficacy and acceptability of agomelatine compared with placebo in the treatment of major depression.

Method

Randomised controlled trials comparing agomelatine with placebo in the treatment of unipolar major depression were systematically reviewed. Primary outcomes were (a) Hamilton Rating Scale for Depression (HRSD) score at the end of treatment (short-term studies) and ( B) number of relapses (long-term studies).

Results

Meta-analyses included 10 acute-phase and 3 relapse prevention studies. Seven of the included studies were unpublished. Acute treatment with agomelatine was associated with a statistically significant superiority over placebo of –1.51 HRSD points (99% CI –2.29 to –0.73, nine studies). Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo (relative risk 0.78, 99% CI 0.41–1.48). Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission). None of the negative trials were published and conflicting results between published and unpublished studies were observed.

Conclusions

We found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias.

 

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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Looks like the studies showing agomelatine might be a good antidepressant were -- yep -- jimmied to give glowing results. See http://1boringoldman.com/index.php/2012/02/13/a-bad-sign/Recently, agomelatine failed its most recent Phase III clinical trial for FDA approval for distribution in the US.

I am absolutely stunned that this could happen :rolleyes:CS

 

snort!

Started on Prozac and Xanax in 1992 for PTSD after an assault. One drug led to more, the usual story. Got sicker and sicker, but believed I needed the drugs for my "underlying disease". Long story...lost everything. Life savings, home, physical and mental health, relationships, friendships, ability to work, everything. Amitryptiline, Prozac, bupropion, buspirone, flurazepam, diazepam, alprazolam, Paxil, citalopram, lamotrigine, gabapentin...probably more I've forgotten. 

Started multidrug taper in Feb 2010.  Doing a very slow microtaper, down to low doses now and feeling SO much better, getting my old personality and my brain back! Able to work full time, have a full social life, and cope with stress better than ever. Not perfect, but much better. After 23 lost years. Big Pharma has a lot to answer for. And "medicine for profit" is just not a great idea.

 

Feb 15 2010:  300 mg Neurontin  200 Lamictal   10 Celexa      0.65 Xanax   and 5 mg Ambien 

Feb 10 2014:   62 Lamictal    1.1 Celexa         0.135 Xanax    1.8 Valium

Feb 10 2015:   50 Lamictal      0.875 Celexa    0.11 Xanax      1.5 Valium

Feb 15 2016:   47.5 Lamictal   0.75 Celexa      0.0875 Xanax    1.42 Valium    

2/12/20             12                       0.045               0.007                   1 

 

I'm not a doctor. Any advice I give is just my civilian opinion.

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"substantial publication bias"

 

Oh No! cannot be! Big Pharma luvs us all, they would never...

 

sigh...

Started on Prozac and Xanax in 1992 for PTSD after an assault. One drug led to more, the usual story. Got sicker and sicker, but believed I needed the drugs for my "underlying disease". Long story...lost everything. Life savings, home, physical and mental health, relationships, friendships, ability to work, everything. Amitryptiline, Prozac, bupropion, buspirone, flurazepam, diazepam, alprazolam, Paxil, citalopram, lamotrigine, gabapentin...probably more I've forgotten. 

Started multidrug taper in Feb 2010.  Doing a very slow microtaper, down to low doses now and feeling SO much better, getting my old personality and my brain back! Able to work full time, have a full social life, and cope with stress better than ever. Not perfect, but much better. After 23 lost years. Big Pharma has a lot to answer for. And "medicine for profit" is just not a great idea.

 

Feb 15 2010:  300 mg Neurontin  200 Lamictal   10 Celexa      0.65 Xanax   and 5 mg Ambien 

Feb 10 2014:   62 Lamictal    1.1 Celexa         0.135 Xanax    1.8 Valium

Feb 10 2015:   50 Lamictal      0.875 Celexa    0.11 Xanax      1.5 Valium

Feb 15 2016:   47.5 Lamictal   0.75 Celexa      0.0875 Xanax    1.42 Valium    

2/12/20             12                       0.045               0.007                   1 

 

I'm not a doctor. Any advice I give is just my civilian opinion.

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