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Altostrata

One theory of antidepressant withdrawal syndrome

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Downbutnotout

 

 

On 5/24/2011 at 10:59 PM, Altostrata said:

THIS IS THE FIRST POST OF THIS TOPIC. LINK TO FULL POST

 

Admin note: For discussion of lamotrigine (Lamictal), see Lamictal (lamotrigine) to calm post-discontinuation withdrawal symptoms

 


 

 

This following is an article that has propagated all over the Web, by someone named Altostrata. It has been updated for this post:

As I've been suffering from Paxil withdrawal syndrome since October 2004, I've studied the medical literature on antidepressant withdrawal syndrome. What I've learned about the alerting system and glutamatergic system in antidepressant withdrawal syndrome may be informative.

Antidepressants cause downregulation of serotonin receptors. In a mechanism of brain self-defense, the receptors actually disappear, becoming more sparse so as to take in less serotonin. It is thought among withdrawal researchers that people who experience the worst withdrawal are slower than others to repopulate serotonin receptors.

Others believe those who suffer the worst are those whose brains are highly neuroplastic and adapted more thoroughly to the influence of the medication.

Relative slowness to upregulate receptors doesn't mean there's anything intrinsically wrong with our brains, it just means there's variability (of course) among nervous systems.

Even among people suffering the most severe antidepressant withdrawal syndrome, repopulation of serotonin receptors probably occurs long before symptoms disappear. However, while the serotonin system is repairing itself, an imbalance occurs in the autonomic nervous system. The locus coeruleus "fight or flight" center becomes disinhibited and the glutamatergic system becomes more active than normal. This is called disinhibition of the alerting system, and it generates symptoms that are awful: panic, anxiety, sleeplessness, and dreadful imagery among them.

 

... link to rest of this post

Stas you might want to read this. This is what I had seen.

Edited by scallywag
delete multiple quoted posts, edit quote by adding link to post loaction

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whatthelol

I like this explanation of withdrawal syndrome as it relates to sleep homeostasis dysregulation and other kinds of extremely "wired but tired" states not physiologically possible naturally and makes perfect sense. However I think it's only a part of the story. It doesn't explain all the odd visual/sensory/perceptual disturbances that happen and get worse long after the drugs are out of the system, especially if tapered too quickly or cold turkey, which are most definately neurotransmitter related.

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Altostrata

Those symptoms are related to neurotransmitters only in the sense that neurotransmitters and other hormones are the way signals are transmitted throughout the body. They are autonomic symptoms.

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manymoretodays
On 6/21/2011 at 10:39 AM, Altostrata said:

I have verified the information in post #1 with a knowledgeable doctor.

 

I have also been corresponding with Dr. Giovanni Fava. Dr. Fava has not only been a longtime critic of antidepressants, he an expert in Cushing's syndrome, a disorder involving excessive cortisol production due to tumors. (The cortisol production in Cushing's is far, far higher than in withdrawal syndrome. Symptoms of Cushing's include fatigue; muscle weakness; depression, anxiety and irritability; loss of emotional control; cognitive difficulties.)

 

Dr. Fava's theory that antidepressants worsen the course of depression, instilling a greater likelihood of relapse in those who take them, has been getting more attention lately. His statistics of relapse (and those of Dr. Irving Kirsch, see Do Antidepressants Make You Sad?) are based on existing research.

 

I have long contended that many of those post-antidepressant cases of relapse recorded in psychiatric research are actually withdrawal syndrome, from which you may recover. Therefore, while Dr. Fava's theory seems likely in light of existing research, if withdrawal syndrome were factored in, it would show that antidepressants are not effective and increase the risk of withdrawal syndrome rather than relapse.

 

This last week, Dr. Fava and I had this exchange regarding Do Antidepressants Make You Sad?:

 

 

Just quoting this one as..........my brother was in town recently and while visiting a friend of his.........I was referred to a book written by a local pediatrician.     And I WILL search for it.  She, our friend, said it was about how AD's don't work.  And God Bless him........and I so hope he is still practicing, working with the children.  The pediatrician is her brother.  He may well be retired now.

 

About that march???!!!  I mean it's March now.  We best get organized......:o:)

 

Peace, harmony, healing and all that......

mmt

Edited by manymoretodays
oh, I always elaborate somewhere

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BCangel62

Thank you for sharing your knowledge and insight. It helps me to think more carefully about withdrawal and the introduction of  'New' medications. It's like, maybe I'd better be done with the withdrawal process before deciding to add something new into the mix. At least then I'll know if symptoms are from withdrawal or from a new medication.

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FarmGirlWorks
On 3/12/2018 at 2:29 PM, manymoretodays said:

About that march???!!!  I mean it's March now.  We best get organized......:o:)

@manymoretodays: I'm in! Maybe we could do something like the Womxn's March where there were marches in different cities. I got Seattle 🙂

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bubbles
Quote

 

Dr. Fava's theory that antidepressants worsen the course of depression, instilling a greater likelihood of relapse in those who take them, has been getting more attention lately. His statistics of relapse (and those of Dr. Irving Kirsch, see Do Antidepressants Make You Sad?) are based on existing research.

 

I have long contended that many of those post-antidepressant cases of relapse recorded in psychiatric research are actually withdrawal syndrome, from which you may recover. Therefore, while Dr. Fava's theory seems likely in light of existing research, if withdrawal syndrome were factored in, it would show that antidepressants are not effective and increase the risk of withdrawal syndrome rather than relapse. 

 

 

This. I wonder how much of the "worsening" is just that people are being inappropriately put onto meds, and then inappropriately withdrawing from them. I hope that's the case, anyway.

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TriD

The title information has been very valuable to me.

 

i have found my symptoms of what I consider the brain have mostly gone and is now replaced by symptoms that are fight-flight in nature.

 

the symptoms that I feel are related to upregulation of receptors have seem to cleared, I even believe that my brain has completely restored itself, as I was on SSRI for only 6 months overall.

 

the issue I have now seem CNS related and it’s usually the agitation and anxious jittery type feeling, unable to focus or stay still, it’s like being in a nervous state without external factors causing it, it comes and goes but it is mild.

 

this also influences my thoughts, an anxious body will create anxious thoughts. Sometimes I feel like someone with GAD, although before SSRI I was a very cool customer.

 

ive tested the idea with taking a myriad of supplements, ie. nootropics and also vitamins..they have initial calming effects followed by the contradictory effects for hrs following, and this I believe is the triggering of the autonomous fight flight mechanism. I even reduce my doses eg. 5HTP to 20% of the recommended dose and got quite severe reaction which could last a day, and the reaction feels very CNS and not like WD symptoms,

 

another is low resislience, when I am having a nice conversation with friends I will suddenly feel agitated, spaced out and numb, and the need to lie down after 15 mins of stimulation.the same occurs with stress, the tolerance level is quite low, compared to my normal self before SSRI, I could have hr long heated debates or party all night, even backpack across Europe for months. The shocks were easily shouldered. I am surprised that coming off lexapro left me in such a weakened state, I can barely enjoy a conversation for more than 15 min before feeling overwhelmed.

 

i can only give this time and hope I recover, as said, the paradigm shift occurred and the symptoms I felt with initial discontinued have turned into what feels more link CNS.. pardon me if I don’t know the medical language for this, but the feeling and experience is certainly different. I can test this just by taking some tryptophan or SAMe, even fish oil or vitaminB and in a few hrs I will being to feel very uncomfortable. Even things like coffee and nicotine can cause me to feel this internal buzzing which quickly turns into a throbbing headache..now in the past I could easily slam down 5 coffees a day or stack up piles of vitamins with little effect. Its a big difference today, so I am sure there is something that needs healing until things go back to normal

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tmzddz

Hello, regarding this statement, "Antidepressants cause downregulation of serotonin receptors. In a mechanism of brain self-defense, the receptors actually disappear, becoming more sparse so as to take in less serotonin. It is thought among withdrawal researchers that people who experience the worst withdrawal are slower than others to repopulate serotonin receptors"  can someone explain the process to reverse this? What makes the receptors come back/go back to normal? Does it happen automatically with the absence of the SSRI?

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herod
10 hours ago, tmzddz said:

can someone explain the process to reverse this? What makes the receptors come back/go back to normal? Does it happen automatically with the absence of the SSRI?

It happens on its own, but also on its own time. It's been almost a year and I still have debilitating symptoms.

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tmzddz

Herod, thanks for responding. I'm sorry you still have debilitating symptoms. I am in a bad way myself, so I understand and am sending you (((HUGS))).

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Ryguy
On 5/24/2011 at 7:59 PM, Altostrata said:

Admin note: For discussion of lamotrigine (Lamictal), see Lamictal (lamotrigine) to calm post-discontinuation withdrawal symptoms

 


 

 

This following is an article that has propagated all over the Web, by someone named Altostrata. It has been updated for this post:

As I've been suffering from Paxil withdrawal syndrome since October 2004, I've studied the medical literature on antidepressant withdrawal syndrome. What I've learned about the alerting system and glutamatergic system in antidepressant withdrawal syndrome may be informative.

Antidepressants cause downregulation of serotonin receptors. In a mechanism of brain self-defense, the receptors actually disappear, becoming more sparse so as to take in less serotonin. It is thought among withdrawal researchers that people who experience the worst withdrawal are slower than others to repopulate serotonin receptors.

Others believe those who suffer the worst are those whose brains are highly neuroplastic and adapted more thoroughly to the influence of the medication.

Relative slowness to upregulate receptors doesn't mean there's anything intrinsically wrong with our brains, it just means there's variability (of course) among nervous systems.

Even among people suffering the most severe antidepressant withdrawal syndrome, repopulation of serotonin receptors probably occurs long before symptoms disappear. However, while the serotonin system is repairing itself, an imbalance occurs in the autonomic nervous system. The locus coeruleus "fight or flight" center becomes disinhibited and the glutamatergic system becomes more active than normal. This is called disinhibition of the alerting system, and it generates symptoms that are awful: panic, anxiety, sleeplessness, and dreadful imagery among them.

This paper explains the mechanism in withdrawal causing alerting disinhibition: Harvey, et al: Neurobiology of antidepressant withdrawal: implications for the longitudinal outcome of depression; Biological Psychiatry. 2003 Nov 15;54(10):1105-17.

Once disinhibition of the alerting system takes hold, it becomes self-perpetuating. The whole question of neurotransmitter imbalance -- a chimera of psychiatry anyway -- becomes moot. No manipulation of serotonin, norepinephrine, or dopamine is going to help. In fact, it usually makes the condition worse.

Noradrenergics -- buproprion or Wellbutrin; mirtazapine or Remeron; SNRIs such as Cymbalta, Serzone, Effexor; and St. John's Wort, rhodiola -- stimulate "fight or flight" activation, as will most SSRIs. Drugs and substances that are stimulating should be avoided.

Even drugs that are calming may cause a paradoxical reaction as the alerting system fights to stay in control.

My guess is: The first phase of withdrawal, the acute phase, is the initial shock of withdrawal, with the most defined symptoms, such as brain zaps and nausea and possibly waves of unusually intense "depression" and "anxiety" -- actually, emotions generated by the neurological upset. Later, glutamatergic hyper-reactivity and autonomic instability take over. Often the autonomic instability causes wide hypersensitivity to drugs, supplements, and even foods.

Out of control, unrelated to environmental or psychological triggers, the alerting system sends intense, spontaneous signals to the adrenals, which produce the stress hormones cortisol and adrenaline.

This is not strictly brain damage. Brain damage means some physical part has been permanently removed and can never be recovered. Rather, this is iatrogenic neuropsychiatric damage.

According to established principles of neuroplasticity, the nervous system can repair itself and regain functioning that is close to normal. In cases where there is no apparent iatrogenic cause for autonomic dysfunction, it often spontaneously resolves. Low stress, good nutrition, and as much sleep and gentle exercise as possible are key.

[ironically for those suffering from lamotrogine (Lamictal) withdrawal -- too-fast Lamictal withdrawal causing glutamatergic rebound -- lamotrigine is a drug that tempers the activity of the glutamatergic system, incidentally reinforcing an intact GABA system. Microdoses of lamotrigine can assist recovery from antidepressant withdrawal syndrome. I am being treated with about 5mg per day and it is helping me recover.

Cautionary note: Lamotrigine may not be a universal treatment for withdrawal syndrome. If you want to try it, make sure you consult a doctor who is very familiar with using it and start with very small doses -- .5mg to begin, slowly titrate up to 5mg or more; stay at the lowest effective dose. Nausea and headaches are signs of too high a dose. (2mg tablets are available by request from GlaxoSmithKline; 5mg tablets are available by prescription; lamotrigine can be made into a liquid by a compounding pharmacy.) In too large a dose, lamotrigine, like everything else, can make your symptoms worse.]

In the medical literature on antidepressant withdrawal, symptoms of alerting system disinhibition -- anxiety, panic, sleeplessness, irritability, agitation among them -- are sometimes misidentified as "unmasking" or emergence of bipolar disorder. This leads the clinician to medicate with a cocktail of drugs upon which the patient does poorly, the neuropsychiatric damage from antidepressant withdrawal being compounded by additional medication and attendant reactions.

In Anatomy of an Epidemic, Robert Whitaker describes this process as the way many children, suffering adverse effects from antidepressants, are led into a lifetime of medications for misdiagnosed bipolar disorder.

It's always the victim who's blamed, not the drug. It's about time we took a closer look at what withdrawal does to the nervous system, and question whether the chronic downregulation of serotonergic receptors caused by long-term antidepressant prescription is a benign condition.

 

 


For discussion of lamotrigine (Lamictal), see Lamictal (lamotrigine) to calm post-discontinuation withdrawal symptoms

 

Two questions:

 

if downregulation leads to an excited rebound effect that can last for years. Is there any evidence of how to regrow receptors?

 

second thing, you said the brain can repair itself close to normal? Does close to normal mean not entirely normal?

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Altostrata

You can't do anything about downregulation except to let your body go through natural processes to re-calibrate receptors. Not much is known about this process. For some people, it seems to be very gradual and take a long time.

 

As the process takes a long time, some years may pass. Your body and brain naturally want to get back to normal functioning. "Normal" may change as years go on. You can never step in the same river twice.

 

For example, if you went on antidepressants when you were 19 and went off when you were 34, your brain and nervous system will not revert to what you remember "normal" to be as a 19-year-old. That's life.

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Ryguy
2 hours ago, Altostrata said:

You can't do anything about downregulation except to let your body go through natural processes to re-calibrate receptors. Not much is known about this process. For some people, it seems to be very gradual and take a long time.

 

As the process takes a long time, some years may pass. Your body and brain naturally want to get back to normal functioning. "Normal" may change as years go on. You can never step in the same river twice.

 

For example, if you went on antidepressants when you were 19 and went off when you were 34, your brain and nervous system will not revert to what you remember "normal" to be as a 19-year-old. That's life.

ok so we don't know how up regulation works. got it. 

 

but by "normal" you dont mean it can cause permanent changes or damage to the brain, but that the natural aging process will continue 

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Altostrata

The aging process, whatever you've done while you're recovering, your general health -- they all affect your "normal" at any one time.

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crashcourse
On 5/25/2011 at 7:59 AM, Altostrata said:

The locus coeruleus "fight or flight" center becomes disinhibited and the glutamatergic system becomes more active than normal. This is called disinhibition of the alerting system, and it generates symptoms that are awful: panic, anxiety, sleeplessness, and dreadful imagery among them.

This paper explains the mechanism in withdrawal causing alerting disinhibition: Harvey, et al: Neurobiology of antidepressant withdrawal: implications for the longitudinal outcome of depression; Biological Psychiatry. 2003 Nov 15;54(10):1105-17.

Noradrenergics -- buproprion or Wellbutrin; mirtazapine or Remeron; SNRIs such as Cymbalta, Serzone, Effexor; and St. John's Wort, rhodiola -- stimulate "fight or flight" activation, as will most SSRIs. Drugs and substances that are stimulating should be avoided.

 

Alto, could you please clarify the bolded statements. These appear to be contradictory, the way I understand them.

 

So you're saying the WD effect leads to activation of fight and flight. I read this as stimulating the LC and Amygdala.

 

In the second statement: SSRIs are also stimulants. (presumably for the same fight and flight centers.)

 

I always thought SSRIs depressed the flight/fight activity, thus decreasing anxiety and other emotions.

 

Am I getting this wrong?

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