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Damaged by SSRI - Let's find those genes!

Messages
42
Location
Balatonfüred
Hi!

I'm planning on collecting genes that are related to suffering prolonged or permanent brain,liver etc. damage from previous SSRI use.
Don't want to go into too much details,some info about me:
23 years old male,first used SSRIs at age 17 due to bullying and traumas after traumas.
Been on Paxil (called Rexetin where I live) and 2 other ones that I don't even remember because I suffered amnesia.Those 3 years I've been poisoning myself with the drugs have been erased from my memory.

There were several symptoms like bruxism that went on for 6+ months and later on caused the back of my tooth to break in half.
There are persistant symptoms like ED,inability to concentrate,depersonalization,derealization.
Basically that feeling you get when the summer breeze caresses your skin or when something exciting is happening to you and you get shivers,whole body electric sensation is gone for years now.

In 2011 April I was fed up with feeling like a zombie with no energy and decided to quit cold turkey from 10 mgs.
I feel like I'm in a video game with the adequate blunted emotions and cannot complish simple tasks that I've used to be able to.I've lost the charming person and character that I was before and got a more serious workaholic,perfectionist,researching one to find answers to this misery.
This wouldn't be a problem if I could get rid of the less desirable side effects.

My symptoms range from PSSD,POIS,blunted emotions,paranoia,racing thoughts,delusional thinking,Alzheimer's like memory,chronic fatigue,weight gain on waist-stomach-face and developing a feminime figure,lack of motivation and most importantly I do think that my serotonin gets downregulated too quickly and I need to find alternative ways to resensitize the 5HT receptors.
In layman's term I give you an example: this means that I don't enjoy my favorite songs I used to listen over and over again,the way I did.
I need to find newer and newer things to stimulate my brain.
My serotonin levels get so low that if I don't listen to music my vision gets blurry,my muscles get rigid and I can't get up from the chair.But if I do,then my vision clears up and I get a burst of energy to even do hand stands.This only lasts for a few minutes and I get extremely tired due to weak adrenals.

So in short this is what SSRIs did to me and I never imagined 2 years ago that after discontinuation my life will never be the same,infact I've never got rid of any symptoms associated with these poisons.
....The past month I've tried to study for my exam and my brain does not agree with me.I have to stop in the middle of a sentence due to forgetting what I wanted to say.I just wish someone would understand me and wouldn't label me lazy or unmotivated. :cry:


My theories are the following:

- There are certain people who are genetically predisposed to permanent physical brain changes despite time and dosage from taking SSRIs.

- The toxins get stored in the body fat but SSRIs can cause you to develop hypothyroid,hypogonadism etc. so you will have no chance to lose that weight and not only because of them but because ;

- It damages the liver. I do think these drugs cause liver damage and inability to detoxify the neurotoxins.Just need to hear stories from other people who have their livers tested prior to use and afterwards.

- Most importantly,you born with faulty genes that are just waiting to be expressed as soon as you pop that bad boy the first time.


I wrote this all in frustration and hope that if you people help me find genes associated with this then we can defeat this monster and help fellow sufferers to beat prolonged SSRI discontinuation syndrome.
My first candidate would be the one that is also associated with Post Traumatic Stress Disorder.
It's called RORA and you can find it on your 23andme.I'm homozygous for it.
Thanks for reading.

Istvan
 

Tammy

Senior Member
Messages
2,176
Location
New Mexico
The typical way most doctors deal with depression is to raise the serotonin with ssri's but they fail to address the other side of the coin which also involves raising your catacholamines with l-tyrosine or phenylalanine. Have you ever had your neurotransmitters tested?
 

Lotus97

Senior Member
Messages
2,041
Location
United States
People who are COMT probably aren't going to want to try raising their dopamine or norepinephrine, but I'm sure there's exceptions.
 

PDXhausted

Senior Member
Messages
258
Location
NW US
I'm not in any way an expert on this, but the first thing that came to mind is detoxification. Paxil is cleared through CYP2D6. Maybe run your 23andme results through the detox profile on geneticgenie.org and see if you have any polymorphisms there.

This chart is a handy reference:
http://medicine.iupui.edu/clinpharm/ddis/table.aspx

That said, if you did have a polymorphism in CYP2D6, I'm not sure if that would account for long term damage from the drug. Perhaps there was an interaction with the other drugs you were on as well.

I don't know much about neurotransmitters, so I don't know how to interpret your symptoms. But I will just offer an anecdote-- I know someone who suffers from depression and has tried several SSRI's including paxil and did well on them. He tried 5-HTP alone and it just made him sleepy. But when he tried taking Vitamin B6, it made him feel alot brighter and gave him more energy. Apparently Vitamin B6 is used in the conversion of 5-HTP to serotonin. So for his particular situation, I'm guessing he doesn't utilize B6 efficiently, and it took more supplementation for him to convert to serotonin. So that is something to think about. I can't figure out which SNPs would account for the B6 utilization though.
 

Jarod

Senior Member
Messages
784
Location
planet earth
Hey Steve,

Sounds like a tough situation. For what it is worth, some of the symptoms can fluctuate pretty wildly with this disease. Hope you can get some of that straightened out.

Not sure if you saw this article about how anti-depressants can raise risk for gastro-intestinal infection. Stomach and liver issues especially have to potential for affecting mood and well being.

Haven't begun learning about the genes yet. Maybe something good will come up on your thread.

Take care,
Jarod



 
Messages
42
Location
Balatonfüred
"Chronic treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization of 5HT1A receptors even after removal of the SSRI in rats.[25] These long-term adaptive changes in 5-HT receptors, as well as more complex, global changes, are likely to be mediated through alterations of gene expression.[26][27][28][29][30] Some of these gene expression changes are a result of altered DNA structure caused by chromatin remodeling,[31][32] specifically epigenetic modification of histones[33] and gene silencing by DNA methylation due to increased expression of the methyl binding proteins MeCP2 and MBD1.[34] Altered gene expression and chromatin remodeling are also involved in the mechanism of action of electroconvulsive therapy (ECT).[35][36]
Because described gene expression changes are complex, and can involve persistent modifications of chromatin structure, it has been suggested that SSRI use can result in persistently altered cerebral gene expression leading to compromised catecholaminergic neurotransmission and neuroendocrine disturbances,[11] such as decreased testosterone levels[37], reduced sperm counts[38], and reduced semen quality with damaged sperm DNA[39]. However, without detailed neuropsychopharmacological, pharmacogenomic and toxicogenomic[40] research, the definitive cause remains unknown."

  • I just know that epigenetics are part of this puzzle and hopefully we'll be able to find a way to silence the genes responsible for this.
  • This will be another key component me thinks.
 
Messages
21
Location
near LA, California
I'm not in any way an expert on this, but the first thing that came to mind is detoxification. Paxil is cleared through CYP2D6. Maybe run your 23andme results through the detox profile on geneticgenie.org and see if you have any polymorphisms there.

This chart is a handy reference:
http://medicine.iupui.edu/clinpharm/ddis/table.aspx

That said, if you did have a polymorphism in CYP2D6, I'm not sure if that would account for long term damage from the drug. Perhaps there was an interaction with the other drugs you were on as well.

I don't know much about neurotransmitters, so I don't know how to interpret your symptoms. But I will just offer an anecdote-- I know someone who suffers from depression and has tried several SSRI's including paxil and did well on them. He tried 5-HTP alone and it just made him sleepy. But when he tried taking Vitamin B6, it made him feel alot brighter and gave him more energy. Apparently Vitamin B6 is used in the conversion of 5-HTP to serotonin. So for his particular situation, I'm guessing he doesn't utilize B6 efficiently, and it took more supplementation for him to convert to serotonin. So that is something to think about. I can't figure out which SNPs would account for the B6 utilization though.

Can you tell me how to read the chart? I know what the indicators across the top like 1A2 mean. Are these lists of things we will have problems clearing and will stay in our bodies longer if we take them? For instance I have several heterozygous 2D6 SNPS. Does that make the antidepressants listed under 2D6 contraindicated for me?
Thanks.
 

PDXhausted

Senior Member
Messages
258
Location
NW US
I should re-iterate that I'm not an expert in this area, and would defer to anyone with better biochemistry knowledge, but here is my basic understanding--- it depends on whether the SNPs you have are up-regulations or down-regulations. If the polymorphism is an up-regulation, that means you may metabolize a drug that is a substrate of that cytochrome faster (and thus may need more to feel the effect of it). If the SNP is a down-regulation, that means you may metabolize the drug slower and thus may need a lower dose.

As for interpreting the chart, I believe the substrate section are drugs that are metabolized through those cytochromes. The inducer section are substances that stimulate production of that cytochrome, thus making more of it. And the inhibitor section are substances that reduce the availability of the cytochrome.

You could try and search through PubMed for both the SNPs and the specific drugs you are concerned with, and see if there is any specific research available. And of course talk to your prescribing doctor too :)
 

Bluebell

Senior Member
Messages
392
My first candidate would be the one that is also associated with Post Traumatic Stress Disorder.
It's called RORA and you can find it on your 23andme.I'm homozygous for it.
Istvan

Istvan, which one? 23andMe says that there are 429 SNPS for RORA!
 

Hip

Senior Member
Messages
17,820
There are some treatments suggested for post-SSRI sexual dysfunction in this article here, including the drugs bupropion and pramipexole, and the supplement yohimbine. I wonder if these might be generally beneficial for log term SSRI-casued lingering effects?