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what meds decrease amygdala activity?

meds social anxiety high serotonin discussion amygdala activity progesterone overactive amygdala

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#1 kurdishfella

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Posted 01 September 2017 - 11:46 PM


I need a medication/drug that decrease amygdala activity , I know propranolol does  this but the effect is only 4 hours I need a more longer lasting one.


Edited by farshad, 01 September 2017 - 11:46 PM.


#2 Mind_Paralysis

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Posted 02 September 2017 - 09:17 AM

FINALLY!

 

 

Propranolol is a good drug, it's often prescribed for anxiety actually - all you have to do, is redose! = )

 

With that said... here are some other drugs:

 

 

Guanfacine (intuniv, tenex) - Alpha-2a-agonist, used for the treatment of ADHD and high blood-pressure (notice that much like propranolol, it's a drug modulating norepinephrine)

 

HydroxyNorKetamine (Alpha-7-antagonist - the nicotinic Alpha-7-receptor controls much the activity in and out of the amygdala, by antagonising it, activity is drastically reduced, also a weak NMDA-antagonist, offering another pathway towards the relief of anxiety)

 

DEhydroNorKetamine (even more potent Alpha-7-antagonist, much more selective than HNK, less other effects)

 

Memantine (alpha-7-antagonist, however this effect is weak, but it makes up for it in spades with NMDA-antagonism)

 

 

Obviously the ketamine-metabolites are hard to come by, but the norepinephrine-modulators, Propranolol and Guanfacine are not.

 

I believe you tried Memantine without effect? Not sure how that is at all possible, but I suppose that's not necessarily a drug which is going to help you then.



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#3 kurdishfella

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Posted 02 September 2017 - 12:32 PM

no I did not try Memantine  or Guanfacine . I wanna try propranolol again I belive my dosage was off.. you said something about propranolol dosage and weight?



#4 kurdishfella

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Posted 02 September 2017 - 02:53 PM

what do you think about citalopram?https://www.ncbi.nlm...les/PMC2802527/



#5 Mind_Paralysis

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Posted 02 September 2017 - 09:23 PM

what do you think about citalopram?https://www.ncbi.nlm...les/PMC2802527/

 

I think it's a decent drug, there's some proof that Escitalopram, a closely related drug, is ever so slightly more effective for Depression though, so if you have that as well, that might be a better bet.

 

It should be noted that there is apparently evidence for not just Citalopram, but for Escitalopram and several other SSRI's to decrease amygdal activity.

 

 

I suggest you COMBINE both an SSRI, and another, more directly acting amygdala-damper to get a robust enough effect in decreasing anxiety.

 

 

F*** it, you're such a serious case, that I'd probably suggest this combo:

 

Propranolol

Memantine

SSRI

 

You need the whole works. Though, not necessarily at the same time, try Prop and Esci together first, and then combine with Mem if needed. It should be noted btw, that yes, if you decrease activity too much, you'll kind of become... ROBOTIC. Of course, after having as much anxiety as you have, this may not necessarily be a negative, at least for the first few weeks. One can always alter dosing later.

 

 

 

Refs:

------------

Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients

https://www.cambridg...2EFD0A4BBC8FAEC

 

Escitalopram effects on insula and amygdala BOLD activation during emotional processing

https://www.ncbi.nlm...les/PMC2839135/
 



#6 kurdishfella

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Posted 02 September 2017 - 10:41 PM

so how much Propranolol do i need to take? you said it had to be the right amount for my weight to work.  . what effects can happen   if i decrease my amygdala activity?


Edited by farshad, 02 September 2017 - 10:42 PM.


#7 Sleepdealer

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Posted 03 September 2017 - 11:22 AM

Escitalopram is a viable alternative. I've been on it for almost a year now and can testament that it helped a lot with bringing anxiety down. It's like it turns down the volume of the significance of things, kinf of like how Edward Norton explains it in Fight Club. :) It can be a relief. That being said, the first 1-2 weeks I had some initial bouts of nausea back and forth which then subsided. I also experienced anorgasmia when I went from 10 mg to 20 mg, which is the lowest therapeutic dose, but was ameliorated once I went back to 10 mg, and 5 mg, half a tablet. IMO it works really fast. So it can be an option. But there is a couple of side effects. Also, monitor yourself carefully so you can adopt to any alterations of behaviour when you are testing different substances.


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#8 kurdishfella

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Posted 03 September 2017 - 02:30 PM

what about Guanfacine  @stinkorninjor? you left that one out its a possibility .



#9 Mind_Paralysis

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Posted 03 September 2017 - 09:01 PM

what about Guanfacine  @stinkorninjor? you left that one out its a possibility .

 

What do you mean? I listed it earlier. If you're wondering if there's any specific dosing there, then the answer seems to be no - if you try it, you simply have to try the dosages out and see which one works the best.

 

I'm too tired to dig up the info on Propranolol dosing, but google for "dose-dependent amygdala propranolol" and "converting from mouse to human dosing" and I'm pretty sure you'll find it.



#10 kurdishfella

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Posted 05 September 2017 - 09:34 PM

 

what about Guanfacine  @stinkorninjor? you left that one out its a possibility .

 

What do you mean? I listed it earlier. If you're wondering if there's any specific dosing there, then the answer seems to be no - if you try it, you simply have to try the dosages out and see which one works the best.

 

I'm too tired to dig up the info on Propranolol dosing, but google for "dose-dependent amygdala propranolol" and "converting from mouse to human dosing" and I'm pretty sure you'll find it.

 

ok i will try them.. will taking propranolol or any of these drugs decrease the production of serotonin in the amygdala? according to this people with social phobia produce too much serotonin in the amygdala in social situations http://www.uu.se/en/...rticle/?id=4918

 

overactive amygdala info

https://inside-the-b...ctive-amygdala/

http://www.dana.org/...s.aspx?id=42898

https://www.ncbi.nlm...les/PMC2882379/

https://inside-the-b...ctive-amygdala/


Edited by farshad, 05 September 2017 - 09:45 PM.


#11 kurdishfella

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Posted 18 September 2017 - 04:51 AM

I was thinking wellbutrin+abilify+memantine combo
maybe add Guanfacine too for more effect on the amygdala.cant i just take regular ketamine or does that not work?

Edited by farshad, 18 September 2017 - 04:52 AM.


#12 Mind_Paralysis

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Posted 18 September 2017 - 11:47 AM

I was thinking wellbutrin+abilify+memantine combo
maybe add Guanfacine too for more effect on the amygdala.cant i just take regular ketamine or does that not work?

 

Don't use all of these, NEW, drugs which you haven't tried before, all at once - wait at least a few days in-between introducing them.

You may not need all of them, and some of them might even be detrimental.


I suggest you start with Aripiprazole (abilify) and Memantine first, and then add Wellbutrin if needed. A word of caution btw... Aripiprazole and Wellbutrin are BOTH known to cause impulsive behaviour and HYPERsexuality - i.e, you could temporarily become a gay cross-dresser who gambles away all of his money.

It's not a common combination, so it's hard to tell if the drugs would enhance or weaken each others such effects when combined - please be careful... you don't want to do something which you could end up regretting for the rest of your life.

 

And no, you can't take regular Ketamine, that's not how it works. Regular ketamine is a lot better as an antidepressant, not an anxiolytic. Please remember that Ketamine affects a F*CK-load of receptors and often causes addiction, inebriation and hallucinations - you wouldn't be able to socialize or operate complex machinery or do anything else complex, if you used Ketamine daily.

 

Tha'ts just not how it works.

 

This is the reason why they invented 6-HydroxyNorKetamine - it doesn't have those side-effects.


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#13 kurdishfella

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Posted 19 September 2017 - 01:43 AM

oh okay. Will try 1 med at a time.

 

if you are wondering my thought process and How I came up with these meds well here it is:

 

well First of the Abilify To increase or should I say Balance Dopamine levels.

 
Second Wellbutrin to Increase Norepinephrine.
(Wellbutrin is a weak Dopamine med btw thats why I added abilify)
 
Memantine or guanfacine to decrease amygdala activity.
 
So now that I have my dopamine in check. Norepinephrine in check. Amygdala in check. 
last part is my Serotonin levels.. Will these meds all together be enough to get rid of the excess serotonin or do I need some sort of Serotonin antagonist? I have been looking at Zyprexa and risperdal but I dont know for sure if they do decrease serotonin or if there is a better med for this?  well I guess I will just have to try and see theres no way to know.

Edited by farshad, 19 September 2017 - 01:45 AM.


#14 kurdishfella

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Posted 19 September 2017 - 03:33 AM

hmm actually might just buy memantine and agomelatine from https://www.ceretropic.com/
Agomelatine both increase dopamine and Norepinephrine . Lol. No need for a doctor .


one other thing can memantine shrink the amygdala since it reduces its activity? =less overall fear?

Edited by farshad, 19 September 2017 - 04:11 AM.


#15 kurdishfella

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Posted 19 September 2017 - 09:51 AM

Agomelatine is a 5-ht2c antagonist.. I wonder if this makes it so it reduces serotonin too in the brain?
But im worried about the short half life only 2 hours making the drug ineffective.

 



#16 Mind_Paralysis

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Posted 19 September 2017 - 11:09 AM

Agomelatine won't have any effect on your symptoms.

It's never prescribed for anxiety because it DOESN'T affect that. It's a weak antidepressant, probably best for sleep-issues than anything else.

 

You seem to be missing that the primary effect of Agomelatine is on Melatonergic receptors - the 5ht2c-antagonism is quite weak - even Mirtazapine is a more powerful 5ht2c-antagonist than Agomelatine.

 

It can also cause issues with the LIVER, meaning that you can't drink when you take it, and it could be problematic for someone like you, who's also taking several other medications metabolised by the liver. Leave this one alone, it won't help.

 

 

As for the effects... they remain longer than the drugs half-life - this is a COMMON effect in drugs - some drugs cause changes which remain after the drug is gone. Other examples are the opioids - many of them only have such a short half-life, some even SHORTER than Agomelatine, but the effects can last for hours. Atomoxetine is another example, wherein the effects of the drug last 2-3 times longer than the half-life, this is why it's only prescribed once daily, even though the half-life is short.

You also have to take into account that some drugs also have active metabolites, meaning that once the body has broken down ONE compound, it then suddenly just finds itself facing ANOTHER compound, just as powerful, and perhaps altering the brain in very similar ways, to the drug that was just broken down. Bupropion is one such example - it has multiple active metabolites, which contribute to the effects - ONE of them, is actually many times stronger than Bupropion itself.

 

You have to stop looking so superficially at drugs - the way they work is almost always a lot more complicated than it may first seem, even when they have simple mechanisms of action. (and none of the drugs you have selected, other than possibly agomelatine, have anything close to a simple mechanism of action)


Edited by Stinkorninjor, 19 September 2017 - 11:10 AM.


#17 kurdishfella

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Posted 19 September 2017 - 11:43 AM

Well I have no choice. I have to try it to see if it works. What do you suggest? Go with the first combo I said? Would probably take ages to get abilify and wellbutrin.

 I also saw a comment about agomelatine effect on the 5ht2c someone was saying it was weak and a person replied Binding affinity alone does not determine the potency of a drug. Whatever that means .

 

these are all the meds I have tried and the only one that worked was zyprexa which I belive is because of the 5-ht2c effect. I dont take any meds btw atm.

 

zyprexa

lexapro 
sertraline
buspar
Celexa
PAXIL 
Prozac 
Nardil
propranolol 
klonopin 
Alimemazine 
Venlafaxine
Bisoprolol
LYRICA
diazepam
tianeptine 
seroquel
Cyproheptadine 
Reserpine
lergigan
Atarax
phenibut
kratom
St John's Wort 
arctic root


#18 Mind_Paralysis

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Posted 19 September 2017 - 02:20 PM

Why did you stop taking Olanzapine (zyprexa) if it had good effects on your anxiety? I'm guessing there were troublesome side-effects? There are ways around some of the side-effects though, so consider going on it again.

 

Btw, don't assume 5ht2c-antagonism was what helped you, because Olanzapine (zyprexa) is actually more selective for multiple other receptors. Here, have a look at this quick ranking of receptors with greater affinity (lower numbers actually mean GREATER effects on those receptors):

 

H1 2.19 Inverse agonist. Likely responsible for the sedative effects of olanzapine.[7]5-HT2A 2.4 Inverse agonist. May underlie the "atypicality" of the newer antipsychotics like olanzapine. May contribute to sedating effects. D2 3.00 Antagonist. Likely responsible for the therapeutic effects of olanzapine against the positive symptoms of schizophrenia.[7]M5 7.5 Antagonist. 5-HT6 8.07 Antagonist.

 

And then you have the 5ht2c:

 

5-HT2C 10.2 Inverse agonist. May underlie the appetite-stimulating effects of olanzapine. 5-HT2B 11.9 Inverse agonist/antagonist.

 

Look at how close the 5ht6 and 5ht2b -affinities are, as well...

 

 

So, looking at the actual affinities, wouldn't you actually say that it's more plausible that it's the 5ht2a and D2 -antagonism that would be beneficial? Read up on what the other 5ht-receptors it effects stronger than 5ht2c does, and then re-evaluate which actions you actually want - you also have to take into account that sometimes these receptors, depending on what part of the brain they're located in, doesn't always do exactly the same thing...

 

For instance, some 5ht2c-antagonists cause increased appetite - but others do not. (agomelatine is one of those that don't - which stumped scientists at first, before they realized it must be more complicated than what they had assumed)

 


Edited by Stinkorninjor, 19 September 2017 - 02:21 PM.


#19 kurdishfella

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Posted 19 September 2017 - 02:40 PM

i got zyprexa to calm me down from the hospital once since it was acute.

all these stuff is making me confused. I have an appointment with my doc on monday gonna ask for memantine and agomelatine and if she says no i will ask for abilify (looks like abilify has some sort of effect on 5ht2c too) and wellbutrin

also progesterone I think it blocks 5ht2c too could be wrong which would make sense since when i took a high dose of progesterone i felt really good..

https://www.ncbi.nlm.../pubmed/9878811

#20 kurdishfella

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Posted 19 September 2017 - 04:09 PM

I think  Dizocilpine is the most potent 5HT2c antagonist.



#21 Rob Roy

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Posted 20 September 2017 - 03:07 AM

i got zyprexa to calm me down from the hospital once since it was acute.

all these stuff is making me confused. I have an appointment with my doc on monday gonna ask for memantine and agomelatine and if she says no i will ask for abilify (looks like abilify has some sort of effect on 5ht2c too) and wellbutrin

also progesterone I think it blocks 5ht2c too could be wrong which would make sense since when i took a high dose of progesterone i felt really good..

https://www.ncbi.nlm.../pubmed/9878811

 

Many antipsychotic drugs increase progesterone, so there is a relationship.  

 

Abilify was mentioned a few times, but I suggest:

Seroquel

Gabapentin

 

Valium is a better option than most realize.



#22 kurdishfella

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Posted 20 September 2017 - 03:54 AM

 

i got zyprexa to calm me down from the hospital once since it was acute.

all these stuff is making me confused. I have an appointment with my doc on monday gonna ask for memantine and agomelatine and if she says no i will ask for abilify (looks like abilify has some sort of effect on 5ht2c too) and wellbutrin

also progesterone I think it blocks 5ht2c too could be wrong which would make sense since when i took a high dose of progesterone i felt really good..

https://www.ncbi.nlm.../pubmed/9878811

 

Many antipsychotic drugs increase progesterone, so there is a relationship.  

 

Abilify was mentioned a few times, but I suggest:

Seroquel

Gabapentin

 

Valium is a better option than most realize.

 

Yeah I heard zyprexa increases progesterone too

https://www.ncbi.nlm...pubmed/12496935



#23 kurdishfella

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Posted 20 September 2017 - 11:23 AM

ehh might just ask for zyprexa on monday it worked last time. not gonna take any chances with the other meds they might not work. Im just so tired of waiting, im just watching my life go by.  . First of all it takes ages to get an appointment. and when you do get one your chances of getting a med is 1 in 1000 . And getting the med u ask for 1 in 10000 .

Well I have an autism  diagnosis . and I think zyprexa is used for autism too?  so hopefully it increases my chances of getting it.


Edited by farshad, 20 September 2017 - 11:24 AM.


#24 kurdishfella

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Posted 21 September 2017 - 01:27 PM

Out of the 25 meds only Zyprexa and Diazepam (vallium) worked.

 

Zyprexa: 

  • Specifically, antagonist actions at 5HT2C receptors may contribute to efficacy for cognitive and affective symptoms in some patients
  • 5HT2C antagonist actions plus serotonin reuptake blockade of fluoxetine add to the actions of olanzapine when given as Symbyax (olanzapine-fluoxetine combination)


See I am on the right track. . Zyprexa blocks 5ht2c.

 

Diazepam:

  • Inhibits neuronal activity presumably in amygdala-centered fear circuits to provide therapeutic benefits in anxiety disorders

So from this I can gather that any drug that has a strong antagonism  effect on Serotonin receptors (specifically 5ht2c) and or reduce my amygdala activity will produce anti anxiety effect for me.

 

 

And Abilify is a partial agonism on 5ht2c .I dont know what that is? does that mean it balances the activity?

And if memantine can reduce amygdala activity maybe I am on to something here.

and wellbutrin just for the energy boost and motivation

 

and the good thing all these 3 drugs have a Long half life.

hmm maybe i should just play it safe  and go with zyprexa and wellbutrin. Yeah.

 

 

And also I am curious why propranolol did not work for me? it doesent add up? do I have to take it every 4 hours to keep the effect going or something? Or was my dosage low? I remember taking like up to 200mg propranolol... 

 


Edited by farshad, 21 September 2017 - 01:41 PM.


#25 Mind_Paralysis

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Posted 21 September 2017 - 03:42 PM

You have to take propranolol continously, I believe. HOWever... 200 mg is way, waaay too much! The effect on the amygdala has a very small window - if you overshoot it, it will stop decreasing activity - the mouse-studies showed this - that's why it's important to dose according to weight. More isn't always better.

 

Also, you should have told us that you have autism as a secondary diagnosis... this is very, very important information.

 

With Autism, I recommend you focus on Olanzapine (zyprexa) - it is indeed used for emotional distress and aggressive behaviour in people with Autism. Remember, not everyone responds with FEAR when their anxiety is triggered, instead they project their emotions externally, and this then shows up as anger. Olanzapine is a very powerful medication for such issues.

 

I would also look closer into MEMANTINE - since Memantine has shown some potential in treating autism as well - the more powerful variant of Memantine, NITROmemantine, actually showed effects on the CORE symptoms of Autism! : D Autistic rats given the drug became more socializing and showed less stereotypic behaviour ("stimming" as it's called - when a person with autism bobs back and forth, or fiddles rhytmically with their fingers or something like that)

 

Recent data have shown that the NMDA-network is implicated in Autism - it seems to be TOO active! This is supported by data which shows that people with autism have errors in their metabolism of TRYPTOPHAN - the amino-acid which is later transformed into the body's OWN NMDA-antagonist - Kynurenic Acid. I put a lot of research into this matter, since some people with ADHD have shown similar errors and Memantine is helpful to some.

(I abandoned this later, when I realized that I have ADD/SCT/CDD, which is a disease badly studied, hence there's no proof yet that the NMDA-network is involved with that disorder)

 

 

I'd forget about Bupropion (voxra, wellbutrin), since there's not really any proof that it helps with anxiety, it's not prescribed for GAD or Social Anxiety or anything like that. It also works, partially, in reverse of something like Olanzapine (zyprexa).

 

Go with Olanzapine and Memantine - the combo could be GOLDEN for you! = )



#26 kurdishfella

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Posted 21 September 2017 - 04:14 PM

I belive my autism diagnosis is wrong tho...I dont really have it I can be social if it wasnt for this damn social anxiety.

But this opens the possiblility of more meds so its better for me.

I will on monday mention all the meds we discussed here:

Zyprexa, Memantine, Wellbutrin,abilify . will try to get as many as possible.  But doctors here in Sweden well atleast in my experiences them willing to prescribe a med is like winning the lottery.

Isnt risperdal a more potent version of zyprexa? If you look at the pharamoclagy on Wikipedia of this drug its  an antagonist on everything almost.

But yeah I will go with the zyprexa and memantine and try to get wellbutrin too because I heard it can increase motivation and energy. I will try one at a time to see which one works.

Also what do you think of diazepam? the first benzo I tried (bought it online) and it worked well .. removed my anxiety by like 70% . Assuming its one of the weak benzos I imagine xanax is a lot stronger.


Edited by farshad, 21 September 2017 - 04:40 PM.


#27 Mind_Paralysis

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Posted 21 September 2017 - 05:07 PM

Potency isn't everything, you have to weigh in the side-effects - you don't know for SURE that Risperidone (risperdal, et c) will work for you - but you DO know that Olanzapine worked, hence it's a safer bet to go back to that again, and try some different doses, before you start using a different antipsychotic.

Remember that there are subtle differences between these drugs, and not all of them fit everyone - even a small difference in pharmacology can give BIG side-effects for some people - that's why there are so MANY atypical antipsychotics, you need different ones for different people.

 

 

Benzo's are addictive sh*t and you need to stay away from them. That's what I think.

 

They're not a viable long-term alternative, and you need a LONG-term alternative - please understand that Benzo's ALL cause tolerance, that's how people start abusing them - eventually it wouldn't work.

 

So, when you need something long-term, why even bother with something like that? It's just a waste of time.


Edited by Stinkorninjor, 21 September 2017 - 05:10 PM.


#28 sentics

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Posted 21 September 2017 - 08:18 PM

before embarking on zyprexa, google zyprexa + diabetes. there are people claiming they got diabetes years after discontinuing zyprexa. others who connect weight gain and subsequent diabetes to zyprexa and so on.

 

don't want to be alarmist, i've taken it myself and it did work well, just be aware that there is this risk and educate yourself about it.


Edited by sentics, 21 September 2017 - 08:19 PM.


#29 Mind_Paralysis

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Posted 22 September 2017 - 09:38 AM

before embarking on zyprexa, google zyprexa + diabetes. there are people claiming they got diabetes years after discontinuing zyprexa. others who connect weight gain and subsequent diabetes to zyprexa and so on.

 

don't want to be alarmist, i've taken it myself and it did work well, just be aware that there is this risk and educate yourself about it.

 

What is the proposed mechanism behind this metabolic alteration?

 

In theory, he should be able to buy a blood-glucose tester and see if his levels are ok, and thereby circumvent any such issues - if they go awry, he can start tapering the drug, and perhaps test another antipsychotic.

 

Apparently, there's a home test for INSULIN levels being worked on! The successful study was 6 years ago, so in theory, it could be on market now, or very, very soon.

 

 

https://www.scienced...10224103240.htm

 

https://www.thediabe...es-test-strips/
 

 

With these, he wouldn't need to worry about such things, he could measure it and be completely safe. Once a week should be sufficient to detect alterations.



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#30 kurdishfella

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Posted 22 September 2017 - 10:53 AM

I will try do stay on the lowest dose of zyprexa possible that works for my anxiety. I think I got 2.5mg when I got zyprexa for the first time . And it made me sleepy and sedated as hell. A lot stronger than seroquel. Maybe thats why it helped with anxiety the zyprexa.. i was too tired and sleepy to care?

 

I Wonder if abilify also increases progesterone.


Edited by farshad, 22 September 2017 - 11:17 AM.






Also tagged with one or more of these keywords: meds, social anxiety, high serotonin discussion, amygdala activity, progesterone, overactive amygdala

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