Valdoxan (agomelatine) the atypical antidepressant

[rafiki]

I've just been prescribed this by my doctor for depression. It's a melatonin receptor agonist and a serotonin receptor antagonist, so it theoretically should be perfect for HPPD. It only takes two weeks to start taking effect. I'm quite excited to start taking it tomorrow night, and I'll post some updates with my progress. 

[mgrade]

Hmm.  So apparently it has the half life of a vitamin and has only 1% bioavailability.  But I guess knowing all that it appears at least safe, I guess.  Some say it can reset circadian rhythms.  Others say it's kind of a garbage drug (maybe along the lines of buspirone). 

Tell us what you think of it.  

I think they said it was aromatic with some lighter fluid thrown on it.  Loll

Edited May 10, 2018 by mgrade

[rafiki]

People on the internet say a lot of things. Clinical studies however are showing it to be one of the most effective antidepressants around with the least side effects.

[rafiki]

Day 4, and so far I love this stuff. I've been much calmer, and I'm waking up feeling refreshed. It hasn't worsened my hppd. I'll update again after two weeks, but I'm definitely planning to continue using it.

[Guest]

Nice. Have you heard of Tianeptine? Sounds similar.

 

[Onemorestep]

“The impact of agomelatine on glutamate signalling has been examined as this excitatory amino acid neurotransmitter and its receptors play a role in depression and antidepressant activity (Mitchell and Baker, 2010). Drugs with glutamate-based mechanisms are endowed with accelerated onset of activity. Currently, the non-competitive NMDA receptor antagonist ketamine appears an attractive therapeutic agent for treatment-resistant patients with depressive disorder (Machado-Vieira et al., 2009). However, the cognitive and dissociative side effects of ketamine limit its widespread application. The exact implication of glutamate in depression and antidepressant treatment is far from clear because of the many interactions with other neurotransmitter systems, for example through kinase phosphorylation and BDNF synthesis in the case of ketamine (Autry et al., 2011). A number of other drugs [e.g. selective GluN2B receptor (NR2B) antagonists, positive modulators of AMPA receptors, and metabotropic glutamate (mGlu) receptor agonists/antagonists for nomenclature see Alexander et al., 2013a] also exhibit antidepressant-like effects in animal models of depression (Hashimoto, 2011), but no clinical studies demonstrating the effectiveness of these drugs are available.

Through a synergistic interaction between its MT1/MT2 and 5-HT2C receptor components, agomelatine modulates glutamate signalling, engaging time-dependent modifications of receptors and transporters in circumscribed regions involved in the regulation of mood, circadian rhythms and cognition (Racagni et al., 2011). Thus, the acute administration of agomelatine (40 mg·kg−1 i.p.) abolishes the restraint stress-induced increase in extracellular glutamate efflux in limbic structures such as the basolateral and central nuclei of the amygdala and the hippocampus (Reagan et al., 2012). As previously found with other antidepressants (Bonanno et al., 2005), chronic administration of agomelatine (40 mg·kg−1, i.p., for 21 days) significantly reduced endogenous release of glutamate from hippocampal synaptosomes and decreased the accumulation of SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) complex, a key molecular effector of vesicle docking, priming and fusion at presynaptic membranes (Milanese et al., 2013). Long-term administration of antidepressants elicits adaptive changes in the functional status of mGlu receptors (Paul and Skolnick, 2003; Palucha and Pilc, 2007). This is also the case of chronic agomelatine, which normalizes glutamate release and the expression of mGlu2/3 and mGlu5 receptor mRNAs in the hippocampus of rats subjected to prenatal restraint stress (Morley-Fletcher et al., 2011; Marrocco et al., 2014). Further, chronic agomelatine treatment modulates the expression of mGlu receptor mRNA in a time- and region-dependent manner (Varcoe et al., 2009). For example, agomelatine increases the evening expression of mGlu1, mGlu4, mGlu6 and mGlu8 receptors in the frontal cortex, while some transcripts can be over-expressed in the morning (mGlu7) and at night (mGlu8). Other time-dependent changes are induced by agomelatine, for example in the SCN (where mGlu7 receptor levels increased at night and decreased during subjective day). Those changes in the timing of glutamate receptors could be conveyed by rhythmicity of certain CLOCKgene's transcription factors (Varcoe et al., 2009).”

 

Fascinating. This is something I’d like to look into.

[rafiki]

6 hours ago, TheMythos said:

Nice. Have you heard of Tianeptine? Sounds similar.

 

Yes - I actually used some in the early days that I bought online. It wasn't anywhere near as effective for me. It didn't worsen symptoms from memory though either.

 

I believe that agomelatine is probably the most effective antidepressant that's suitable for people with HPPD. I'm still dealing with the knock on effect of five days of ssri's last month, and i think it's making me appreciate this drug even more.

[Guest]

Apparently I can't get this in the US because it was never submitted to the FDA for approval by Novartis...

"While agomelatine may be relatively well tolerated during shorter clinical trials, often times more serious adverse effects are seen with long term use and this appears to be the case with agomelatine. Long term use of agomelatine was found to be associated with liver damage and its use in the markets it is approved in is contraindicated in patients with impaired liver function.

Impaired liver function in individuals is fairly common. Even the presence of elevated liver enzymes may preclude the use of agomelatine. If agomelatine were to be approved and used in the United States, routine lab monitoring of liver enzymes and function would be recommended throughout treatment."

Did your doctor mention this Rafiki?

Edited May 17, 2018 by Guest

[Onemorestep]

Man I was going to order some of this stuff in October and didn’t get around to it. About a month later I came across something that made me think “holy shit thank god I didn’t take that.” But for the life of me I can’t remember what it was or where I found it. I just remember knowing that I would have had a horrific reaction to it had I tried. If I can remember what it was I’ll post it.... but I’m glad to hear it isn’t doing that to you!! Remember to keep an eye on your liver

 

i beleive you can buy buy this in the USA from ceretropic.

[rafiki]

I'm having regular liver tests yes. My doctor said the incidence of liver damage isn't much higher than some ssri's, but because it's fairly new they have to do it.

When I looked it up it was about 5% for ago and 3.6% for lexapro.

In Australia you don't get any rebate on it, as it's not a first line treatment. Costs about $50 a month. So far it's definitely worth it.

[rafiki]

I've now been on this drug for 2 and a half weeks, and to be honest I've had a couple of anxious days recently. I'm not feeling the same strength of effect as I felt at first. I might need to see my doctor and up the dose a bit I think.

What are other HPPD-friendly anti-depressants? vortioxetine? Bupropion?

[Onemorestep]

On 5/17/2018 at 10:40 PM, Onemorestep said:

Man I was going to order some of this stuff in October and didn’t get around to it. About a month later I came across something that made me think “holy shit thank god I didn’t take that.” But for the life of me I can’t remember what it was or where I found it. I just remember knowing that I would have had a horrific reaction to it had I tried. If I can remember what it was I’ll post it.... but I’m glad to hear it isn’t doing that to you!! Remember to keep an eye on your liver

 

i beleive you can buy buy this in the USA from ceretropic.

I realize now I was mixing up agomelatine and Galantamine. Very different drugs haha.

[Onemorestep]

@rafiki did you find something else to ask for?

 

i would show your doctor the quote I posted in this thread about the role agomelatine has on glutamate. Perhaps you can find another medication that explores a similar MoA since you responded well. 

[rafiki]

I'm still taking the agomelatine and it's actually still great. I decided to stick to the current dose. Liver tests have been fine too.

I'd definitely recommend getting this drug for depression if you have hppd.

[rafiki]

Quick update:

 

5 months in and I'm still taking this tablet every day. It doesn't improve the HPPD, but it definitely helps with depression. I've had some pretty serious things go on in my life over the last year, and people are commenting on how well I'm doing.

Again, I'd recommend this. It's HPPD-safe and effective.