# 2016 Medicines in Development for Mental Health



## Gelon (Sep 10, 2016)

A list of drugs in development in 2016, do you see something interesting?

http://phrma.org/sites/default/files/pdf/medicines-in-development-drug-list-mental-illnesses.pdf

[SzAdmin / Editor note: Some of the medications on this list have already been cancelled due to poor test results - such as the Forum Pharmaceuticals drug targeting cognition. ]


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## TDX (Jul 12, 2014)

-ALKS-5461 (Kappa-Opioid-Antagonist)

-CERC-501 (Kappa-Opioid-Antagonist)

-NSI-189

-naloxone nasal spray

-PF-04958242 (AMPA-receptor-modulator)

-pomaglumetad methionil (mGlu2/3-agonist)


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## TDX (Jul 12, 2014)

There are some drug forums where they took the AMPA-Antagonist Perampanel together with Ketamine. Perampanel abolished the effects of Ketamine and there is a paper, where it was conjectured that an AMPA-Antagonist could not only work against DP, but also in cases that are resistant to Lamotrigine.

But there is another interesting thing about Perampanel. In a very high dosage it seems to be able to induce DP-Symptoms, too. That's why it was placed in Schedule III in the USA. This raises the question if the mechanism that induces the DP is the same like in NMDA-Antagonists (increased release of glutamate) and Lamotrigine works against AMPA-Antagonist-induced DP, too. I even got another idea: If AMPA-Antagonists work against NMDA-Antagonist-induced DP, maybe NMDA-Antagonists work against AMPA-Antagonist-induced DP?

If this was true, and both "models" have some relevance for DPD, this could mean that all the NMDA- and glycin-antagonists, that are tested against depression, could possibly work for some people against DPD, too. Of course all these NMDA-Antagonists should not cause DP, like Ketamine, but as far as I know, they are built in such a way, that they avoid this effect.

I think the first glycin-antagonist (or is it weak partial agonist?) to be released is Rapastinel. I think it could be a wise idea to try it, when it becomes available.


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## hidden (Nov 28, 2015)

The obvious one I see is: *Pimavanserin*, a 5-HT2A inverse agonist

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Technically not a MID for 2016 but was in 2014/2015 I believe.


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## TDX (Jul 12, 2014)

It seems to be unique in this regard, but I do not really see why it could help against DPD.


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## luctor et emergo (May 22, 2015)

TDX said:


> There are some drug forums where they took the AMPA-Antagonist Perampanel together with Ketamine. Perampanel abolished the effects of Ketamine and there is a paper, where it was conjectured that an AMPA-Antagonist could not only work against DP, but also in cases that are resistant to Lamotrigine.
> 
> But there is another interesting thing about Perampanel. In a very high dosage it seems to be able to induce DP-Symptoms, too. That's why it was placed in Schedule III in the USA. This raises the question if the mechanism that induces the DP is the same like in NMDA-Antagonists (increased release of glutamate) and Lamotrigine works against AMPA-Antagonist-induced DP, too. I even got another idea: If AMPA-Antagonists work against NMDA-Antagonist-induced DP, maybe NMDA-Antagonists work against AMPA-Antagonist-induced DP?
> 
> ...


So Perampanel is an option for us, as lamotrgine and / or leviracetam didn't have a positive effect on dp, dr.


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## TDX (Jul 12, 2014)

I think so. At least some theoretical stuff speaks for it, but we do not know for sure, because it was never tested for DPD. We also do not have anecdotal evidence. On dpselfhelp.com a person announced to try it, if his response to other medications was insufficient, but he never came back. But he may be a special case, because his symptoms were induced by mushrooms:

http://www.dpselfhelp.com/forum/index.php?/topic/42157-topiramate-log-and-other-pharmacological-musings/

So far, nobody with DPD tried it. In a study it induced "depersonalization/abnormal thoughts" in 10% of participants. Generally it seems to have psychiatric side-effects:

http://onlinelibrary.wiley.com/doi/10.1111/ane.12529/pdf


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## luctor et emergo (May 22, 2015)

Again excellent find TDX.

Another med for the to try list...


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## hidden (Nov 28, 2015)

TDX said:


> It seems to be unique in this regard, but I do not really see why it could help against DPD.


Pimavanserin is a drug that will be used off-label in EVERY single hospital in the country in the next 5-10 years. It will be used as an 'add-on' to other antipsyche drugs. I see that you have mirtazapine as a drug you are on. I think maybe it is helping with DR. This is a more selective drug (Pimvanserin). The implications of the 'off-label' use is PROFOUND for the treatment of many things.


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## TDX (Jul 12, 2014)

> Of course, it remains unknown whether it's actually the 5-HT2A antagonism that does anything but it does seem to be the major difference between APs that work and APs that don't


The sample size of AAP-responders is very low, but I don't remember anyone who responded to a typical antipsychotic. But David Kozins study suggests that actually AAPs are more likely to increase DP than typicals. This could be chance, because of the low sample size, but I read somewhere that AAPs increase glutamate activity in certain parts of the brain, while typicals do not.


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## TDX (Jul 12, 2014)

> I think the assessment of AAPs given in my Psychiatric MT is fair. They only work in a few (my guess is about 15-20%) of cases but when they do, they're highly effective.


I think the number ist MUCH lower. At least my data suggests this, but in comparison to SSRIs and benzodiazepines the sample size is much smaller and AAP were not widely used, so we shouldn't draw premature conclusions from this.

But in my opinion there are quite a few credible cases where they worked, but there are much more people who got worse. In my opinion it is a very important question WHY antipsychotics can make DP worse in some people. For example in HPPD antipsychotics also increase the symptoms in some people. It was found by Abrahams - one could say he is the "Sierra of HPPD" - that a COMT-Inhibitor with Levedopa worked in 30%, so in this case a dopaminergic treatment exists. There is anecdotal evidence for people with DPD who also respond to stimulants, which are often dopaminergic. Maybe in the DPD there is also a dopaminergic treatment, that nobody is aware of.



> I could be completely wrong but I'm not the first person to hypothesise about a role for 5-HT2A. Sierra has done the same in the past, if I remember correctly.


Simeon thought about it, because LSD activates it, but Cyproheptadine was a failure.


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