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Excitotoxicity: Glutamanergic Hyperactivity Induced Toxicity?


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#1 oskcajga

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Posted 10 February 2017 - 08:07 PM

I rarely post topics like this, but I believe I've finally stumbled upon one of the potential mechanisms behind the symptoms that I've been suffering with for the past several years.  It's in regards to the hypothesized glutamanergic hyperactivity related to downregulation of serotonin receptors, as hypothesized by some prominent members of this forum.  At first I tended to dismiss that hypothesis as simple disregulation which would result in the brain communicating incorrectly with its various regions, but then I did a little bit more investigation and stumbled upon this:

 

https://en.wikipedia.../Excitotoxicity

 

Long Story Short:  Glutamate in the correct proportions is critical for the correct functioning of the central nervous system - but when these proportions change, the effects can be disastrous.   If SSRI users experience chronic downregulation of serotonin receptors, which then causes an uptick in glutamanergic processes - how can one not see the possible connection?  Even short term increases in a "glutamanergic storm" in the brain can cause serious harm in healthy people - what happens when we not only have a glutamanergic storm, but also a hyperactive sympathetic nervous system, and all the downstream effects of increased levels of norepinephrine, cortisol, - changes in acetylcholine, dopamine, thyroid hormones, sex hormones, etc etc etc etc? 

 

It's definitely not good, and anyone who escapes taking antidepressants without long term harm should honestly consider themselves as lucky as someone who manages to walk away from a plane wreck unscathed. 

 

It's hypothesized with a remarkable amount of anecdotal evidence at this juncture that antidepressants can cause neuropathies, this is evidenced by PSSD and various long term symptoms that people who try to stop taking antidepressants experience (eye pain, burning in the head, burning and tingling in the extremities, a "wet glove" sensation along the limbs)". 

 

Dr. Healy considers neuropathies in more detail in this video:

 

(START AT 29 MINUTES): 


8 Words of Wisdom about Adverse Effects and Psychiatric Drug Withdrawal Syndrome:

 

1.  Please do learn about this condition by thoroughly reading 1) Dr. Healy's website and SurvivingAntidepressants.

2.  Please read books like: 1) Anatomy of An Epidemic and 2) Mad in America.

3.  Success Stories do exist.

4.  Please be extremely cautious about reinstatements, recreational drugs, supplements.  Even low doses can complicate matters.

5.  Transfer all financial assets into your own name (hint: relationships end).  Do not spend money wastefully.  Keep your job as long as possible.

6.  Psychiatric drug "withdrawal" and adverse effects are serious neurological reactions to powerful "drugs" - do not take this condition lightly.

7.  These conditions almost never recognized by any medical doctors - hospitalization/appointments can be futile/potentially injurious.

8.  PSSD, anhedonia (no emotions), memory loss, brain zaps, etc are scary - don't worsen them by taking more drugs, supplements, and medications.

 

Stimulant free since September 20th, 2014; SSRI free since September 1st, 2013


#2 powerback

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Posted 15 February 2017 - 10:35 AM

I rarely post topics like this, but I believe I've finally stumbled upon one of the potential mechanisms behind the symptoms that I've been suffering with for the past several years.  It's in regards to the hypothesized glutamanergic hyperactivity related to downregulation of serotonin receptors, as hypothesized by some prominent members of this forum.  At first I tended to dismiss that hypothesis as simple disregulation which would result in the brain communicating incorrectly with its various regions, but then I did a little bit more investigation and stumbled upon this:

 

https://en.wikipedia.../Excitotoxicity

 

Long Story Short:  Glutamate in the correct proportions is critical for the correct functioning of the central nervous system - but when these proportions change, the effects can be disastrous.   If SSRI users experience chronic downregulation of serotonin receptors, which then causes an uptick in glutamanergic processes - how can one not see the possible connection?  Even short term increases in a "glutamanergic storm" in the brain can cause serious harm in healthy people - what happens when we not only have a glutamanergic storm, but also a hyperactive sympathetic nervous system, and all the downstream effects of increased levels of norepinephrine, cortisol, - changes in acetylcholine, dopamine, thyroid hormones, sex hormones, etc etc etc etc? 

 

It's definitely not good, and anyone who escapes taking antidepressants without long term harm should honestly consider themselves as lucky as someone who manages to walk away from a plane wreck unscathed. 

 

It's hypothesized with a remarkable amount of anecdotal evidence at this juncture that antidepressants can cause neuropathies, this is evidenced by PSSD and various long term symptoms that people who try to stop taking antidepressants experience (eye pain, burning in the head, burning and tingling in the extremities, a "wet glove" sensation along the limbs)". 

 

Dr. Healy considers neuropathies in more detail in this video:

 

(START AT 29 MINUTES): 

 

Great  info thanks .truly scary what we face by the sounds of what doctor healy  describes .very interesting towards the end about doctors and there attitude, we are looking at generations before the vast majority change.my own doctor has been hostile to the criticism from me .I've told him on many occasions I believe your trying to help but this is not the way I've learned anymore  I've said to him .

I try to reinforce appreciation for the help ,I want to keep an open dialogue with him so he can see it can be done a different way.

He is actually pretty open minded in other ways ,he's a fan of Eckhart tolle and I've recently told him about gabor mate ,so I believe there is hope  .


21​/06/2012 citrol10mg for stress, constant urination ,diazepam 2mg 26/07/2012 .12/07/2012 citroll 20mg,

​24/09/2013 Lexapro 20mg.didnt take them for a week during this year felt extremely strange ,had no idea down to drugs at the time .

​20/10/2014 venlafaxine xl 75mg.09/01/2015 venlafaxine xl 37.5. questioned doctor about drop in dose ,I was told no problem.

​13/04/2015 venlafaxine xl 150mg NEVER TOOK THEM getting wise?.20/04/2015 venlafaxine xl 75mg.19/08/2015 Xanax 250mcg [agitated]

​10/06/2015 venlafaxine 37.5mg.02/03/2016 five beads out for taper only lasted till 06/06/2016 extreme irritability and anxiety. 

​11/11/2016 Xanax 250mcg took them for few days ,fairly distressing time [working nearly impossible].11/11/2016 I was given a prescription for  Zyprexa 2.5mg AND DECIDED  NOT TO GET IT FROM CHEMIST.[my doctor gave them a great sales pitch ,talking about other patients that have benefited ,in witch it just annoyed me ]


#3 oskcajga

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Posted 20 March 2017 - 07:17 AM

It seems more likely to me that excitotoxitiy would occur after stopping an SSRI rather than during "treatment".  During "treatment", the downregulation of serotonin receptors will be effectuated due to increased levels of serotonin in the synapse which should establish some form of homeostasis between the brain regions that resembles baseline levels.  It's after stopping that the downregulation of the receptors causes the problems described above because there is a lack of serotonin in the synapses while simultaneously your brain is waiting for the 5ht receptors to be re-synthesized. 

 

Perhaps this is why people experience such profound withdrawal reactions:  their body is being overstimulated to the point of possible toxicity.

 

Overall, I think that excitotoxicity is probably just PART of the situation but even if this occurs to a small degree, even for a short period of time (a matter of weeks until serotonin receptors resynthesize) the effects can be quite problematic and probably last for a while.


8 Words of Wisdom about Adverse Effects and Psychiatric Drug Withdrawal Syndrome:

 

1.  Please do learn about this condition by thoroughly reading 1) Dr. Healy's website and SurvivingAntidepressants.

2.  Please read books like: 1) Anatomy of An Epidemic and 2) Mad in America.

3.  Success Stories do exist.

4.  Please be extremely cautious about reinstatements, recreational drugs, supplements.  Even low doses can complicate matters.

5.  Transfer all financial assets into your own name (hint: relationships end).  Do not spend money wastefully.  Keep your job as long as possible.

6.  Psychiatric drug "withdrawal" and adverse effects are serious neurological reactions to powerful "drugs" - do not take this condition lightly.

7.  These conditions almost never recognized by any medical doctors - hospitalization/appointments can be futile/potentially injurious.

8.  PSSD, anhedonia (no emotions), memory loss, brain zaps, etc are scary - don't worsen them by taking more drugs, supplements, and medications.

 

Stimulant free since September 20th, 2014; SSRI free since September 1st, 2013


#4 powerback

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Posted 20 March 2017 - 07:43 AM

hi thanks for this very intersting .

I have got alot of nasty symptoms

 

It seems more likely to me that excitotoxitiy would occur after stopping an SSRI rather than during "treatment".  During "treatment", the downregulation of 5h5 receptors will be effectuated due to increased levels of serotonin in the synapse which should establish some form of homeostasis between the brain regions that resembles baseline levels.  It's after stopping that the downregulation of the receptors causes the problems described above because there is a lack of serotonin in the synapses while simultaneously your brain is waiting for the 5ht receptors to be re-synthesized. 

 

Perhaps this is why people experience such profound withdrawal reactions:  their body is being overstimulated to the point of possible toxicity.

 

hi .this is very interesting ,I'm dealing with a lot of nasty withdrawal symptoms and I'm still on 37.5 ,went off 75mg overnight bout 18 months ago ,so i wonder does this create the same disregulation    in the brain .


21​/06/2012 citrol10mg for stress, constant urination ,diazepam 2mg 26/07/2012 .12/07/2012 citroll 20mg,

​24/09/2013 Lexapro 20mg.didnt take them for a week during this year felt extremely strange ,had no idea down to drugs at the time .

​20/10/2014 venlafaxine xl 75mg.09/01/2015 venlafaxine xl 37.5. questioned doctor about drop in dose ,I was told no problem.

​13/04/2015 venlafaxine xl 150mg NEVER TOOK THEM getting wise?.20/04/2015 venlafaxine xl 75mg.19/08/2015 Xanax 250mcg [agitated]

​10/06/2015 venlafaxine 37.5mg.02/03/2016 five beads out for taper only lasted till 06/06/2016 extreme irritability and anxiety. 

​11/11/2016 Xanax 250mcg took them for few days ,fairly distressing time [working nearly impossible].11/11/2016 I was given a prescription for  Zyprexa 2.5mg AND DECIDED  NOT TO GET IT FROM CHEMIST.[my doctor gave them a great sales pitch ,talking about other patients that have benefited ,in witch it just annoyed me ]


#5 Lakelander82

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Posted 20 March 2017 - 08:51 AM

I never knew Dr David Healy was an Irishman, you learn something new everyday as they say...
May 2007 - October 2007 Citalopram 20 mg od. 1st Antidepressant ever taken. No problem with fast taper and no withdrawal effects. No antidepressants for over 5 years.

January 2013 started Citalopram 20mg.
March 2014 Switched to Sertraline 50 mg od.
23rd June 2016 started taper 45mg
23rd July 2016 40.5 mg of Sertraline
23rd August 36.45 mg of Sertraline
27th September 34.65 mg
24th October 32.90 mg
28th November 31.26 mg
4th January 32mg
25th Feb 31 mg 22nd March 30mg 14th April 29mg