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Altostrata

One theory of antidepressant withdrawal syndrome

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Altostrata

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

Edited by Altostrata
clarification of phases

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Healing

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

This is interesting. From reading lots of people's w/d stories, you can just tell that some people are highly sensitive to any substance, even before they took psych meds.

 

Also, I have always (even before psych meds) been someone who habituated to any substance really fast. I realize this says something about my liver, but mightn't it also have to do with my nervous system?

 

Also, the people who end up in psychotherapy are often the people who are most attuned to their environment -- so the irrationality in their families really affected them, whereas someone else might have shrugged it off more.

 

I've wondered about exactly this -- are those of us who have the hardest time recovering the ones who attuned to the medication most responsively?

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Neuroplastic

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.

This just breaks my heart...

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Claudius

Interesting, I had read many posts of Altostrata on the other site and even exchanged some personal messages with her. She told indeed about her low dose of Lamictal but I really do not want to try another psych med. Besides, Lamictal is from GSK and therefore I have not the slightest confidence in its safety...

I do not think that people with the hardest WD are per definition the most sensitive people to meds. I tried before Valium, Oxazepam and Xanax and none of them had any effect on me. Also I had no noticable effects at starting Paxil, apart for some gaping. But I do think that repeated WD attempts and subsequent reinstatement do havoc on the brain and makes WD even more terrible and recovery slower.

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Claudius

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.

This just breaks my heart...

 

Mine too. Drugging children is really a tragic practice, because they are even more vulnerable and their brains are still in development.

I am a member of a hiking club and one of the persons I sometimes walk with is a psychiatrist. I told her something about my situation, she did not confirm or deny my case. But she told about "treating" children and they were doing so fine after being "adapted to the meds". I did not ask her what would happen if they were taken off the meds... this is probably beyond her way of thinking. And I do not even consider her as a bad person or someone with bad intentions... one time she asked me what I thought of Ritalin. I told her this was a form of amfetamine, the same drug a famous Dutch rock artist and painter used (he comitted suicide about ten years ago by jumping from a famous hotel in Amsterdam). Her answer was that he used "illegal drugs" and those were "not pure".

My reaction was that my life was turned upside down by some legal, chemically "pure" drug. But they are really indoctrinated with their false teachings of psychiatry... when will they start seeing the light?

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Baxter

This information was crucial to my seeing the side effects of my many medications (not all in my sig - not enough room) and my experiences of both withdrawal and poop-out for waht they were.

 

Other folks who suffer in silence need to know.

 

Free association: In the dark ages (1979), there were a couple of horrific rape/aggravated assaults in an area of Boston where working poor, working students, and poor people lived. There were massive massive rallies of women who turned out and marched at midnight to 3 am through the streets of Dorchester, Roxbury and Mattapan...they called the marches Take Back the Night. It got safer for women - in the police stations and hospitals - if not the street. Drugs, psychiatry, help for those in pain needs to be - safer.

 

I am not one of the people who say there is absolutely no place for psycho pharm drugs. My position is more along the line of harm reduction/informed consent. I KNOW engineers who take ritalin, paxil, and klonopin to manage their 65 hour weeks and huge mortgages. They are very intelligent people who make decisions - that suit them...I wonder where they will be when they are 55, but hey I burnewd through two decades without questioning. Until my aging/wacko psychiatrist spilled the beans about poopout.

 

I'm thinking there needs to be a Take Back Our Minds march. From San Francisco to Boston.

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Altostrata

This information was crucial to my seeing the side effects of my many medications (not all in my sig - not enough room) and my experiences of both withdrawal and poop-out for waht they were.

 

Other folks who suffer in silence need to know.....

 

I'm thinking there needs to be a Take Back Our Minds march. From San Francisco to Boston.

 

Baxter, Altostrata will be very gratified to hear that.

 

A march is a great idea.

 

alex, this piece was originally posted on ****** by Altostrata in mid-2010 but, curiously, seems to have disappeared from that site.

 

It was published on Gianna Kali's Beyond Meds (aka Bipolar Blast) blog on July 14, 2010. Someone named Rhiannon was involved in the discussion.

 

Gianna also posted it on benzowithdrawal.com and www.benzobuddies.org. You can find it in Google caches.

 

I was very surprised to find it on stumbleupon http://www.stumbleupon.com/stumbler/wildwoodflwer/review/43928585/ where thanks are given to GiannaKali for the pointer.

 

Altostrata kindly updated it and gave it to me for publication on Surviving Antidepressants.

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angie007

I am very interested in reading this, as here in the Uk lamictal is also called Lamotrigine,

and its and anti seizure medication which my daughter takes for her epilepsy.

 

Does anyone know how this could/might be helpful in ad withdrawal??

Would anyone have any problem with me asking Professor David healy for his take on this??

or maybe Sur would like to do that, but i think he would be interested in this, as he did ask

me some time ago, if i found anything that MIGHT poossibly help to pass it on.

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Altostrata

....Does anyone know how this could/might be helpful in ad withdrawal??

Would anyone have any problem with me asking Professor David healy for his take on this??

or maybe Sur would like to do that, but i think he would be interested in this, as he did ask

me some time ago, if i found anything that MIGHT poossibly help to pass it on.

 

As with anything else, angie, one must find a doctor who is very knowledgeable in using lamotrigine to try anything like this.

 

If you'd like, contact Dr. Healy. Please pass along my e-mail address, as he hasn't answered my e-mails so far. Thanks.

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angie007

Hi sur,

 

Absolutely correct, i think after antidepressant withdrawal, we are all leery,

probably petrified of other drugs if im honest, but if there is the slightest chance

of something that may help, then who better to ask than the expert himself lol.

And of course, i would be glad to pass on your email address, and remind him, he

has not replied to you.

 

I have however googled the mechanics of lamotrigine, and found that its used

off label for Bi Polar patients, not only that, but its been found to work more efficiently

than many of the usual mood stabilisers Lithium etc. It has also proved to b effective in

treating trigerminal neuralgia also.

Of course it works on the brain and nervous system too, so i can see how it MAY be effective

somewhat in relieving Some of the pain we are going through, but.......

sadly i do not understand the mechanics behind this drug, so i thought i might ask the expert

himself, for his take on wether this could be a possible help to any of us suffering here,

through no fault of our own, if no one here mkinds of course!!!!

 

I will also ask too, about any side effects, and how it may help,

I will post back his reply when i receive it.

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alexjuice

As with anything else, angie, one must find a doctor who is very knowledgeable in using lamotrigine to try anything like this.

 

Any advice on how to find a doctor? I've only heard one or two names doing work like this in the entire US. There must be others as I frequently read internet messages about great psychiatrists or neurologists or whatnot, though names/institutions are not frequently included. I have no idea how folks find these docs. I've tried, believe me.

 

Alex.i

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Claudius

Same here in the Netherlands, I have found none. I even wrote to a GP who was in a TV broadcast addressing the issue but he could not do anything else than give me the advive to look for another doctor... but he was not available!

I am aftraif that doctors are very scared to damage their reputation and the mainstream opinion is still that those meds are safe, non addicting and good. We know the stories of dr. Healy who was dismissed from his position at the university of Toronto and MArk Foster who was fired from the hospital he worked for...

Very few have the courage to stand up against the system and risk their job and income. And very few are able to see the enormous lie on which the system is based. The bigger the lie, the fewer people even consider it as a lie. This "technique" was used very succesfully already by Hitler and Goebbels by stupefying and brain-washing the mass, and is now done by Big Pharma.

And in fact I do not need a doctor anymore, time is the only healer for all of us. Unfortunately, some of us need an enormous amount of time...

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Maybe

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.

 

 

Just a short question regarding this paragrapah. I do not want to hijack the thread, but in my case, wouldn't that explain why I was worse after the two acupuncture sessions? As I said, when I was in hospital I had not stress and felt save, which helped my body to slowly recover even if it was still fragile. Those two sessions then aroused the fight and flight system again and my body still has not found it's way back to normal functioning.

 

The weird thing is, I do not have mental but only physical sysmptoms and unconscious anxiety. So everything i now experience is a "out-of-control" nervous system?

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Altostrata

Alex, to find a doctor, I would ask the best doctor I know if he or she can recommend any neurologists or neuropsychiatrists. Then I would start phoning and ask about that person's knowledge of iatrogenic hyper-reactivity and the use of lamotrigine.

 

Neurologist and neuropsychiatrists would be the specialties most likely to know about this. They use lamotrigine to treat seizure disorders. Psychiatrists use lamotrigine for bipolar disorder and tend to overdose it.

 

Do not expect to find someone right away. With every phone call, ask if the person could recommend someone else. Pursue other leads. Keep working at it. You truly are trying to find a needle in a haystack.

 

Maybe, acupuncture can be stimulating, as some psychiatric medications are stimulating. I think you have drawn a reasonable connection between a stimulating treatment and an over-reactive "fight or flight" response.

 

As with most of us, this needs to calm down for recovery, which comes in waves or lurches with a lot of seeming setbacks.

 

As we've discussed before, the acupuncture may have triggered an underlying fragility caused by your severe adverse effect to and subsequent withdrawal from Lexapro.

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Patience

Thanks for posting this Surviving. This article makes a lot of sense and gives me hope. I hadn't read it before.

 

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

...

 

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

Boy is that ever me! Prozac had a huge effect on me. Since I've stopped the meds, valerian, melatonin, calcium, and magnesium all cause me to have anxiety (really any supplement gives me anxiety).

 

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.

 

I try so hard to figure out what my triggers are and can never find them. This explains why!

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angie007

Hi Guys,

 

Just to update, i have written to Professor David healy at the cardiff University,

and asked his opinion on Iatrogenic Hyper Reactivity and wether the possible

use of micro doses of Lamotrigine may b benficial in calming all of this down,

and help us in our goal to heal.

 

I am awaiting his reply, and will post back when i receive it, which i hope will

be sooner rather than later.

 

Sur, i have passed on both email addresses for you, and reminded David, that he

has yet to answer your emails, hope he replies soon, to us both lol.

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Phil

It will be interesting to see what David says.

 

Just a thought on the Lamotrigine - wouldnt there be a possible withdrawal reaction from that, if one was to take it? Or would it be a different kind of withdrawal?

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Altostrata

It will be interesting to see what David says.

 

Just a thought on the Lamotrigine - wouldnt there be a possible withdrawal reaction from that, if one was to take it? Or would it be a different kind of withdrawal?

 

Yes, lamotrigine is like other neuroactive medications, you have to taper off it gradually.

 

Lamotrigine does not cause downregulation of any receptors. The way is works is it changes the electrical properties of particular cell walls so they are less reactive to signalling. (It's so complicated, involving the calcium channel, etc. -- perhaps a neurobiologist will explain.)

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Altostrata

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?:

 

Me: For the sake of millions of people (including myself), I hope withdrawal syndrome is a big artifact in those statistics, and that the nervous system can recover from chronic serotonergic downregulation.

 

Dr. Fava: yes, the brain can recover fully, but we need to have more research on it to understand how. This should become a major health priority.

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cinephile

Me: For the sake of millions of people (including myself), I hope withdrawal syndrome is a big artifact in those statistics, and that the nervous system can recover from chronic serotonergic downregulation.

 

 

Dr. Fava: yes, the brain can recover fully, but we need to have more research on it to understand how. This should become a major health priority.

This pithy exchange has just made my day and will go a long way in catapulting you to the cutting edge, Alto. Finally researchers are getting the message that in many cases (most?) relapse = withdrawal. I am very hopeful that research will soon begin on how people can recover from chronic serotogenic down-regulation due to chronic SSRI use, as this is likely the culprit of many so-called "relapses" when people go off meds. It is high time psychiatry begins cleaning up its messes, and kudos to you, Fava, and Kirsch for laying down the gauntlet.

 

We really are in this together: the patients, the bloggers, the journalists like Whitaker, the sensible psychiatrists like Dan Carlat, Mickey (1 boring old man), and John Sorboro, and compassionate, reasonably minded researchers like Giovanni Fava. I fully believe the world is changed by just a few courageous individuals, and the rest follow. Are we the few? At the very least, the truth is on our side.

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Altostrata

I agree, cine, we all add our weight to the tipping point.

 

Dr. Kirsch, who is a statistician, is also aware of this theory and how it may negate all statistics of antidepressant efficacy.

 

I correspond with every researcher and journalist who may be aware of the implications of this.

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Baxter

Time to start the Million Med March!

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cinephile

Dr. Kirsch, who is a statistician, is also aware of this theory and how it may negate all statistics of antidepressant efficacy.

 

I correspond with every researcher and journalist who may be aware of the implications of this.

Alto, you and everyone on this board, are some of the few good people left in this country (see my post "More Americans Giving up on the American Dream" in the DIY editorials section) and its utterly inspiring. I'm so glad you're getting the word out to every professional you can about withdrawal syndrome and its huge role in the studies.

 

God bless everyone on this board!

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Healing

Time to start the Million Med March!

 

Ha ha! Very good! :D

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Crocus

The initial post here is the best description I have read of antidepressant withdrawl. Thank you for that.

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Dani

 

 

 

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. The second phase is when the serotononergic receptors are repopulating, with waves of depression and anxiety. The third phase is when glutamatergic hyperactivity and autonomic instability take over. Often the autonomic instability causes wide hypersensitivity to drugs, supplements, and even foods.

 

 

 

 

What happens when "glutamatergic hyperactivity and autonomic instability take over"??

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Maybe

A myriade of different symptoms on and off, light and intense...

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Phil

Alto - sorry to bring this topic up again, but can you tell me if Lamictal helped you with these issues - did it help depression and anxiety at all? Racing thoughts? Depersonalization? (if you experienced these symptoms, that is).

 

I am still trying to get a prescription for it myself, because my depersonalization and anxiety are so bad. But I have to wait to see a psychiatrist who can prescribe it.

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Altostrata

It definitely helped anxiety, sleep, racing thoughts. By the time I took it, depersonalization had mostly gone away, and it continued to improve.

 

If you get a prescription, get it for 5mg tablets. They're prescribed for children. This would enable you to titrate up carefully.

 

As I posted in your topic, Phil:

 

Guys, I'm not sure about the ad hoc taking of Lamictal. First of all, you need to start at an extremely low dosage, which most doctors will find ridiculous. Too high and it could make you feel worse. And it might not work for everyone, my doctor has his own ways to diagnose who needs what. He doesn't prescribe Lamictal for everyone.

 

Lamictal is by no means a cure-all.

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Nadia

The initial post here is the best description I have read of antidepressant withdrawl. Thank you for that.

 

Ditto. Finding this post when I was on a mad search for answers as to what was happening to me made me cry. It was the first time I felt "YES, that is exactly what I'm going through!"

 

On a side note, the Lamictal/lamotrigine sounds so tempting. I'm trying to have courage in the face of my latest round of anxiety and depression, but it's waning. I think of suicide again way too often, and the thought that there's a pill that could help, not mask symptoms, but help me really GET HEALTHY is intriguing. But I'm skeptical... what makes it different from any psychiatric med? I think it still would have to have a hatchet-like effect with unknown consequences. On the other hand, I start to doubt my brain's natural ability to heal itself (even as I remind myself I am only 13 months into this and I HAVE improved on the whole even in small ways). I'm glad, like my dad's gun, it's not so easy to obtain.

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Altostrata

Sorry, guys, lamotrigine is not a pill to help you get better. It has to be very carefully used by someone who knows what he or she is doing, or it could make you feel worse.

 

Nadia, you've done such a great job of coping with your symptoms. On the average, have they gotten worse?

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Nadia

Hi Alto,

 

No, I would say on the whole they have gotten better, but I think depression has won over. I'm battling it hard, but mixed with the anxiety, it gets the best of me sometimes. I'm trying to think of it as a physical pain (in fact, I have a lot of back pain now as well, which may or may not be withdrawal related)... just sit with it. The desperation slowly builds when days go by without improvement... it makes me realize it's really all about expectation and I need to work on my acceptance. That was the big hurdle that made me get through the worst of what I was going through a few months ago. I know that is where I have to start... not sure why it's proving more difficult this time. Maybe I'm just tired.

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Altostrata

It could very well be withdrawal-related, but since you're going in a good direction overall, my guess is if you work on it, it will improve. Be sure and stay low stress.

 

Best for the holidays to you, Nadia.

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Nadia

You too, Alto. Thanks for all your support and for running this site. It really makes a difference.

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Altostrata

Thanks, Nadia.

 

The theory advanced in the first post of this topic has been corroborated by correspondence with Brian Harvey, lead author of Harvey 2003 Neurobiology of antidepressant withdrawal:

 

I am very glad to see you are recovering from your own nasty experience. I find it especially interesting that you are showing this recovery using lamotrigine, which is a very effective inhibitor of glutamate release. Our studies have strongly implicated altered glutamatergic activity following antidepressant discontinuation/withdrawal, with especially overt activity at NMDA receptors acting to perpetuate the illness via a kindling-like action. One could even consider this to be a useful case report in support of the argument.

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Nadia

Interesting. The quote is from personal correspondence with Harvey, I suppose?

 

I wonder what the depression/anxiety connection is. Why sometimes both, why sometimes one or the other.

 

I guess that's why the newest antidepressant development is going in that direction... including lamotrigine:

 

http://biopsychiatry.com/glutamate-mood.htm

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