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Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent

  1. Yan Li*
  2. Letha Couch
  3. Masahiro Higuchi
  4. Jia-Long Fang and 
  5. Lei Guo,1

+Author Affiliations


  1.  *Division of Genetic and Molecular Toxicology and
  2.  Division of Biochemical Toxicology, National Center for Toxicological Research/U.S. FDA, Jefferson, Arkansas 72079
  3.  Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
  1. 1To whom correspondence should be addressed at Division of Biochemical Toxicology, National Center for Toxicological Research (NCTR), Food and Drug Administration (FDA), HFT-110, 3900 NCTR Road, Jefferson, AR 72079. Fax: (870) 543-7136. E-mail: lei.guo@fda.hhs.gov.
  • Received January 25, 2012.
  • Accepted February 24, 2012.

Abstract

Sertraline, a selective serotonin reuptake inhibitor, has been used for the treatment of depression. Although it is generally considered safe, cases of sertraline-associated liver injury have been documented; however, the possible mechanism of sertraline-associated hepatotoxicity is entirely unknown. Here, we report that mitochondrial impairment may play an important role in liver injury induced by sertraline. In mitochondria isolated from rat liver, sertraline uncoupled mitochondrial oxidative phosphorylation and inhibited the activities of oxidative phosphorylation complexes I and V. Additionally, sertraline induced Ca2+-mediated mitochondrial permeability transition (MPT), and the induction was prevented by bongkrekic acid (BA), a specific MPT inhibitor targeting adenine nucleotide translocator (ANT), implying that the MPT induction is mediated by ANT. In freshly isolated rat primary hepatocytes, sertraline rapidly depleted cellular adenosine triphosphate (ATP) and subsequently induced lactate dehydrogenase leakage; both were attenuated by BA. Our results, including ATP depletion, induction of MPT, inhibition of mitochondrial respiration complexes, and uncoupling oxidative phosphorylation, indicate that sertraline-associated liver toxicity is possibly via mitochondrial dysfunction.



Key words
  • Published by Oxford University Press 2012.

Articles citing this article

  • Sertraline, an Antidepressant, Induces Apoptosis in Hepatic Cells Through the Mitogen-Activated Protein Kinase PathwayToxicol Sci (2014) 137 (2): 404-415




http://toxsci.oxford...127/2/582.short


WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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  • 1 month later...

Trying to keep mitochondrial pages together. 

http://www.badscience.net/2014/03/statins-have-no-side-effects-what-our-study-really-found-its-fixable-flaws-and-why-trials-transparency-matters-again/

 

this I found in a talk about trials.. 

particularly relating to statin drugs damaging mitochondria but I have already found a many antidepressants on the list of drugs that damage mitochondria... this explains a bit about how the drugs damage mitochondria and the results. 

 

"

  1. FloxieHope said,

    April 3, 2014 at 11:00 pm

    When examining Statins, it should be noted that they have been shown to damage mitochondria. Article – www.ncbi.nlm.nih.gov/pmc/articles/PMC2849981/. Mitochondrial damage can account for all of the relevant adverse effects of statins – muscle weakness and damage, loss of memory/cognitive function, diabetes, depletion of glutathione, etc. An interesting feature of mitochondrial injury is that a threshold of damage must be reached before a disease state results (as described in this article – www.ncbi.nlm.nih.gov/pmc/articles/PMC2895369/?report=classic). So, if your study period isn’t long enough, statins truly will have the same number of adverse effects as sugar pills because in a short period of time, the subjects have not crossed their tolerance threshold for mitochondrial damage and no disease state (or AEs) have manifested. It is only with prolonged exposure to mitochondrial damaging chemicals, like statins, that adverse effects manifest.

    If you don’t design your study of mitochondrial damaging drugs to take into account how mitochondria react to assaults – with an initial adaptive response followed by a toxic response (as the peroxynitrite cycle is induced), your results don’t actually say anything notable. If you design your study to take into account the tolerance threshold feature of mitochondria, and the odd delayed response to toxic stimuli that they often display, you will likely find that statins are quite a bit more dangerous than sugar pills.

    I certainly understand that many research scientists don’t have the time or funding to do long-term studies. But don’t worry – the long-term studies are being done – they’re just being done on the population at large. Hence the reason that it is so important to listen to patients who experience adverse effects of drugs over a long period of time.

    Unfortunately, mitochondrial damage is very difficult to fix and stopping treatment with the mito damaging drug does not necessarily stop the mitochondria from continuing to produce damaging ROS (like peroxynitrite) that continue to do damage long after the drug is metabolized.

    ROS produced in damaged mitochondria are associated with every chronic disease there is. You, and all the other MDs out there may want to consider that chronic disease may be the result of these drugs that are tossed about like candy because they have no adverse effects in the short term, and the long-term effects are dismissed because patient reports are “anecdotal.”"

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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same link as above 

"

  1. David Bailey said,

    April 4, 2014 at 4:16 pm

    FloxieHope,

    Thanks for your observations, because I think it is important to try to make sense of the experiences of many statin users. Although statin effects don’t seem to dissipate completely immediately (mine took about 9 months), the stories (anecdotes?) of many people on Dr Kendrick’s site all seem to confirm that thankfully the effects do reverse.

    Moreover, statins block a synthetic pathway that produces more than just cholesterol, and indeed cholesterol is used throughout the body! Dr Kendrick points out that the ‘normal’ level of cholesterol in humans was determined in a very strange way, and using this as a target figure may be quite harmful."

It may be worth taking a look to see what else this Dr Kendrick has to say.... now I am curious. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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http://www.ccjm.org/content/68/7/625.full.pdf

Mitochondrial cytopathy in adults:
What we know so far
"Mitochondrial diseases may also arise
from processes other than germline mutations
in mtDNA. A case of a somatic (acquired)
mutation causing mitochondrial disease was
recently reported.
 
I found this to be a vary informative read.  I would have posted more but for some reason the copy function is suddenly malfunctioning so see the link and read it for yourself.  I think it uncanny how many of the symptom listed there easily explain some of the worst withdrawal cases I have read and about over the years on sites like this much of it I have lived myself.  Recovery...is also interesting could well be the mitochondria have a way of repairing it self to a certain extent if the damage is drug induced and not genetic... could be as the study of this is in its infancy ... there is a long way to go. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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  • 11 months later...

http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2895%2900672-9/references

 

I was looking into movement disorders and came across this. I get the feeling Japanese science is more open-minded than US stuff.

 

Previous studies have shown an association between low serum cholesterol concentration and suicide; however, conflicting results have also been reported. To examine this potential association, cholesterol levels in 99 patients admitted to an emergency ward following an attempted suicide were compared with those in 74 nonsuicidal psychiatric inpatients, and those in 39 psychiatrically normal individuals with accidental injuries. Cholesterol concentrations in suicide attempters were found to be significantly lower compared with both psychiatric and normal controls, when sex, age, psychiatric diagnosis, and physical conditions (serum total protein and red blood cell count) were adjusted for. This significant relationship was observed in mood disorders and personality or neurotic disorders, but not in schizophrenia spectrum disorders. These results support the previous claim that lower cholesterol level is associated with an increased risk of suicidal behavior.

 

Received: June 13, 1995; Received in revised form: December 13, 1995;

2009: Cancer hospital said I had adjustment disorder because I thought they were doing it wrong. Their headshrinker prescribed Effexor, and my life set on a new course. I didn't know what was ahead, like a passenger on Disneyland's Matterhorn, smiling and waving as it climbs...clink, clink, clink.

2010: Post surgical accidental Effexor discontinuation by nurses, masked by intravenous Dilaudid. (The car is balanced at the top of the track.) I get home, pop a Vicodin, and ...

Whooosh...down, down, down, down, down...goes the trajectory of my life, up goes my mood and tendency to think everything is a good idea.
2012: After the bipolar jig was up, now a walking bag of unrelated symptoms, I went crazy on Daytrana (the Ritalin skin patch by Noven), because ADHD was a perfect fit for a bag of unrelated symptoms. I was prescribed Effexor for the nervousness of it, and things got neurological. An EEG showed enough activity to warrant an epilepsy diagnosis rather than non-epileptic ("psychogenic") seizures.

:o 2013-2014: Quit everything and got worse. I probably went through DAWS: dopamine agonist withdrawal syndrome. I drank to not feel, but I felt a lot: dread, fear, regret, grief: an utter sense of total loss of everything worth breathing about, for almost two years.

I was not suicidal but I wanted to be dead, at least dead to the experience of my own brain and body.

2015: I  began to recover after adding virgin coconut oil and organic grass-fed fed butter to a cup of instant coffee in the morning.

I did it hoping for mental acuity and better memory. After ten days of that, I was much better, mood-wise. Approximately neutral.

And, I experienced drowsiness. I could sleep. Not exactly happy, I did 30 days on Wellbutrin, because it had done me no harm in the past. 

I don't have the DAWS mood or state of mind. It never feel like doing anything if it means standing up.

In fact, I don't especially like moving. I'm a brain with a beanbag body.   :unsure:

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If you were to check the spacedoc.com site a retired NASA doctor terribly affected by statin drugs there is a lot on mitochondria damage also the brain needs cholesterol to function right... as one of the links above shows it could be our needs for cholesterol differ.. we are not all the same. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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Recovery...is also interesting could well be the mitochondria have a way of repairing it self to a certain extent if the damage is drug induced and not genetic.

I hope there is some truth in this ...i can remember saying once at pp that i reckon the mitochondria is impaired.

Thought for the day: Lets stand up, and let’s speak out , together. G Olsen

We have until the 14th. Feb 2018. 

URGENT REQUEST Please consider submitting  for the petition on Prescribed Drug Dependence and Withdrawal currently awaiting its third consideration at the Scottish Parliament. You don't even have to be from Scotland. By clicking on the link below you can read some of the previous submissions but be warned many of them are quite harrowing.

http://www.parliament.scot/GettingInvolved/Petitions/PE01651   

Please tell them about your problems taking and withdrawing from antidepressants and/or benzos.

Send by email to petitions@parliament.scot and quote PE01651 in the subject heading. Keep to a maximum of 3 sides of A4 and you can't name for legal reasons any doctor you have consulted. Tell them if you wish to remain anonymous. We need the numbers to help convince the committee members we are not isolated cases. You have until mid February. Thank you

Recovering paxil addict

None of the published articles shed light on what ssri's ... actually do or what their hazards might be. Healy 2013. 

This is so true, with anything you get on these drugs, dependance, tapering, withdrawal symptoms, side effects, just silent. And if there is something mentioned then their is a serious disconnect between what is said and reality! 

  "Every time I read of a multi-person shooting, I always presume that person had just started a SSRI or had just stopped."  Dr Mosher. Me too! 

Over two decades later, the number of antidepressant prescriptions a year is slightly more than the number of people in the Western world. Most (nine out of 10) prescriptions are for patients who faced difficulties on stopping, equating to about a tenth of the population. These patients are often advised to continue treatment because their difficulties indicate they need ongoing treatment, just as a person with diabetes needs insulin. Healy 2015

I believe the ssri era will soon stand as one of the most shameful in the history of medicine. Healy 2015

Let people help people ... in a natural, kind, non-addictive (and non-big pharma) way. J Broadley 2017

 

 

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according to the space doc site CoenzymeQ10 helps to heal mitochondria

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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Hi,it is interesting because last week there was an report on German TV about people who suffered severe trauma.

They were tested before and after therapy-when they were completely healed.

 

In the state of trauma they showed all lower cholesterol and  a change in their genes.

 

After healing the cholesterol and even the genes changed...so what is the chicken and was is the egg?

 

solida

Sept.2007 Citalopram for burn out,reverse reaction

Paroxetin 20mg,5 weeks,had to stop because of reverse reaction

after a manic episode,severe withdrawal hit after 6 weeks,

hospitalization twice,during the first 2 years withdrawal got worse and worse

disabled since

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It would depend on which type of genes.. I am not sure how genes relate to mitochondria 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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