One theory of antidepressant withdrawal syndrome

[Altostrata]

You're doing a great job Googling. I did the same thing to figure it out, for hours each day since November 2004.

 

I'm pretty sure the autonomic explanation is correct for most withdrawal syndrome except for those in whom the stress of withdrawal touches off autoimmune reactions or other pre-existing subclinical illnesses, a much more complex situation, as if autonomic instability isn't complex enough.

 

When I've talked to physicians who've looked into withdrawal syndrome, the autonomic dysfunction paradigm gives us a common understanding.

 

If you're interested, you might rummage in PubMed http://www.ncbi.nlm.nih.gov/pubmed/ for journal articles on withdrawal syndrome. There are a lot more than you'd think. I've posted some of them in our Journals section but we could always use more as you find them.

 

Suggest searching PubMed with these types of key words:

 

paroxetine withdrawal syndrome

fluoxetine withdrawal syndrome

risperdone withdrawal syndrome

venlafaxine discontinuation syndrome

SSRI discontinuation symptoms

SSRI discontinuation akathisia

SSRI discontinuation cardiac

 

and so forth.

[tezza]

http://www.schizophrenia.com/sznews/archives/002883.html

 

I found this interesting and thought others might also.

 

I would like to add that IMO schizophrenia is caused by leaving meds off. That leads to extreme insomnia in some cases. When the brain is deprived of sleep, it will demand it's rest whether the individual sleeps or not.

 

The brain then sleeps although the individual does not. Dreaming occurs while the person is awake, this is then called 'hallucinations'. ( Then it is DXd as schizophrenia) I witnessed this in the case of my own mother.

[hippopotamus]

Hi Alto, or anyone else for that matter,

 

Do you have any idea how your theory would relate to coming off atypical antipsychotics? Obviously the serotonergic down-regulation wouldnt really apply, but how about the other parts of your theory? Any thoughts on that?

[Altostrata]

It seems autonomic dysregulation is a common factor in many withdrawal syndromes, see http://survivingantidepressants.org/index.php?/topic/1586-hochberg-2003-endocrine-withdrawal-syndromes/

 

One might posit that changing hormonal or neurohormonal imbalance by any avenue will lead to a readjusted homeostasis and might lead to autonomic dysfunction if the agent is too precipitously withdrawn.

 

Excellent find, Barb.

 

Correct -- a generic withdrawal syndrome, causing autonomic instability the symptoms of which may vary from individual to individual, fluctuate, and may have different emphases depending on the action of the original drug.

 

You can describe it in endocrinological terms as hypothalamic-pituitary-adrenal axis dysfunction or in neurological terms as autonomic dysfunction. All of the hormonal systems are networked. Mess with one and you mess with all the others.

....

 

[Narcissus]

How does this theory on dysautonomia gel with your description of withdrawal syndrome, Alto?

 

http://www.holistichelp.net/dysautonomia-autonomic-nervous-system-dysfunction.html

 

I apologize if this has already been posted somewhere.

[Altostrata]

Thanks, pgd.

 

That is an alternative medicine blog "hosted and authored by Cynthia Perkins, M.Ed., holistic health counselor, sobriety coach and adult sex educator."

 

In general, the page you've pointed to is a pretty good description of what the autonomic nervous system does. I'm sure many people here intuitively sense their symptoms are due to "an overactive sympathetic nervous system."

 

I believe, however, the list of "Conditions Related to Dysautonomia" is exaggerated somewhat -- they do indeed "have a variety of contributing factors"; she is using the term dysautonomia very loosely.

 

Since the autonomic nervous system is the control system for automatic operations throughout the body, it's going to be involved in practically any ill. And there's no doubt that reducing stress on it is a good idea in any situation.

 

But Cynthia Perkins is calling everything dysautonomia, and that's not quite accurate. She also takes quite a leap speculating about stress-induced neurotransmitter imbalances.

 

So it has some good parts and others that serve Perkins's practice, which is counseling or coaching people in alternative healing methods (http://www.holistichelp.net/counseling.html )

 

Watch out for this, it's bogus:

Neurotransmitter depletion and/or disruption is the primary underlying cause in all mental health conditions and many physiological as well. With a simple questionnaire that costs nothing beyond the phone consult we can screen for crucial neurotransmitters and determine if more advanced testing is called for. Alternatively, we can use a variety of biochemical tests to get a more accurate and thorough picture of neurological function.

And this, questionable (adrenal fatigue is very rare):

Adrenal Burnout and Other Autonomic Nervous System Dysfunction

 

Adrenal fatigue or burnout and overactivity of the sympathetic nervous system is a major contributing factor in most health conditions, syndromes and illnesses, both physical and mental/emotional. Learn the basics of adrenal burnout and autonomic nervous system dysfunction, how it impacts your mental and physical health and what is needed to restore balance through diet, nutritional supplements and lifestyle changes.

[alexjuice]

Cynthia Perkins, M.Ed., holistic health counselor, sobriety coach and adult sex educator.

 

It's good that she doesn't limit her eggs to one basket. /sarc

[Skyler]

 

Cynthia Perkins, M.Ed., holistic health counselor, sobriety coach and adult sex educator.

 

It's good that she doesn't limit her eggs to one basket. /sarc

LOL, got that one Alex.

[Outshined]

In my very humble opinion Alto, you're exactly right on the spot here:

 

It seems autonomic dysregulation is a common factor in many withdrawal syndromes, see http://survivingantidepressants.org/index.php?/topic/1586-hochberg-2003-endocrine-withdrawal-syndromes/

 

One might posit that changing hormonal or neurohormonal imbalance by any avenue will lead to a readjusted homeostasis and might lead to autonomic dysfunction if the agent is too precipitously withdrawn.

 

...I would add, in many cases even if the agent is withdrawn slowly but it had years to disrupt the natural homeostasis of the nervous system.

[cmusic]

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.

 

Hi - just re-read this and it makes sense on many levels. Explains why every blip of stimuli causes intense panic. But, if this is self perpetuating - the more stress the more NMDA receptor up regulation, the more receptors the more stress - how do you break the cycle? Does it just happen over time that this initial stress response reverses itself?

[Altostrata]

Ahhh....I don't know that NMDA receptors upregulate.

 

Yes, the nervous system tends to restore balance, but it repairs itself in patches, and slowly, which is why you get waves and windows.

 

In Symptoms and Self-care, we suggest ways to gently support the nervous system in its repair work.

[cmusic]

Sorry - got it from this synopsis of the article you posted:

 

"Preclinical data also show that antidepressant withdrawal evokes a behavioral stress response that is associated with increased hippocampal N-methyl-D-aspartate receptor density"

 

Making sense of the actual article is beyond my grasp...

[Altostrata]

The chemistry is beyond me, too.

[btdt]

Alto could you give me your opinion on this link please?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681629/

 

 

Also I have had this idea or understanding on what I thought was going on in withdrawal for a long time bases on information I had found.  

Generally and loosely put it went like this:

 

When we take serotonin enhancing drugs the body stops making as much serotonin and some serotonin receptors in the brain shut down.  The reason is the body/brain wants things to be level and senses there is too much serotonin.  This is why after a time on the dose must be increased.  When we quit taking the drug too quickly the low serotonin and lack of receptors now causes a serotonin depletion... supposedly causing all these symptoms. The body takes a long time to increase or decrease anything and works on a feed back mechanism once it knows there is not enough serotonin it gets to work on trying to fix it but it takes a long long time as the body works slowly.  

Now I did not come up with this on my own and did at one time have the documentation to back all this up.  Since me computer hard drive keeps dying I no longer have this information at my finger tips. 

 

I have gone a long time not understanding this process and I know a lot of people want to know the answers.  I have tried countless times to follow your understanding and always I get lost... I keep thinking some day my brain will be healed and I will just get it but to date that has not happened I am not sure if it is me... still or something else.  In the mean time this little theory has served me well enough.  

I am hoping you don't have to understand the process completely to heal from it. 

 

As for Charles site antidepressant facts I think it is the name pineal... that serves me well... in explaining what not to do.. as in eating well and waiting a good long time for recovery to take place.  I can't say all his other stuff is right but I can say his experience spoke to me loud and clear... what he had I had.  As for the vitamins and supplements he suggested starting all things at 1/6 the recommended dose and I liked that to after I had sever reactions to vitamins and supplements...not to mention the smallest amounts of what were suppose to be safe drugs... paradoxical reactions to others.  

 

Still trying to put this together. 

Peace

[Altostrata]

Good to hear about Lamictal. You may have to cope with that cycle-related chaos. If I were you, I wouldn't play with the lamotrigine dose.

[Daveguy2015]

[quote name="Cdav" post="119046" timestamp="1421195002

 

but on people who once consumed amphetamines and after that they had withdrawal and flashback symptoms. Lamictal helped these people recover and have spontaneous remission from their symptoms. That is why my doctor assumed Lamictal might help me too. He said AD's and amphetamines are not too different from each other in the way they affect neurotransmitters, so that was his logic for using Lamictal with me.

 

Hey Cdav , I'm just curious about what you said about amphetamines. So your saying people can have withdrawal from drugs like adderall? I believe I had this. When I stopped Adderall back in 10' I began having anxiety and intrusive thoughts, and then I had depersonalization. Have you ever heard of something like this before?

[Altostrata]

It is a well-known fact that amphetamines and amphetamine analogs like Adderall are addictive in every sense of the word.

[Daveguy2015]

Hey Altostrata, I would like to know specifically if adderall withdrawal can cause these symptoms? Like the depersonalization and anxiety. I had these symptoms and I was confused as to what was happening to me. This is the whole reason I got placed on an SSRI in the first place.

[Altostrata]

Yes, it can. See Drugs.com for adverse effects of Adderall.

[Daveguy2015]

Ok thanks alot.

[MostlyWater]

While I think this theory has some truth to it, I have another idea. SSRI's have been proven to stimulate neurogenesis in the hippocampus. Many scientists now think this is the reason SSRI's only work for some people and not others. It explains why they take 4 weeks to work instead of right away and also explains why when scientists induce low-serotonin in people, they don't always get depressed. Scientists are even trying to create anti-depressant drugs designed specifically to provoke additional neurogenesis in the hippocampus without messing with the serotonin levels. Now, I'm not saying I know all the answers, but I'm a little skeptical of the deregulation theory because it doesn't explain everything for me. I think we should also look at the other effects SSRI's have on the brain. Scientists have yet to understand everything about neurogenesis and why it reduces depression in people when artificially boosted. I suspect things are a lot more complicated than simple deregulation or else you would see more of these long-term symptoms in other drugs which inhibit monamine reuptake. 

[Cdav]

Alto, the physical symptoms were mostly a lot of akathisia and RLS. Creeoy crawly feelings on my head and through my spinal cord. Also felt my head spinning and was having loss of equilibrium and was very clumsy, I'm down to 50 mg again, the restlesness diminished and I feel a little less clumsy but still having RLS. I have had the RLS and crawling sensations off lamical too, but I feel like it worsed with lamictal. I'm going back to 25 mg, try to find that sweet spot you mentioned. I don't know if I was feeling less depressed or just more activated, and was able to do more things, in an uncomfortable and restless way, though. I was really hoping this would help my depression, aside from the akathisia it's the symptom that is most debilitating.

[Altostrata]

It sounds like more than 25mg is too much for you, Cdav.

 

MostlyWater, nobody knows what this purported neurogenesis means. The assumption is that it's a good thing and it's why antidepressants "work," as you've explained. However, that is an unfounded assumption.

 

If antidepressant-induced neurogenesis actually exists (imaging studies being very questionable for this sort of thing), it could mean bad things such as 1) the brain is trying to repair damage; or 2) normal pruning activity has been stymied.

 

The studies showing neurogenesis are written up as biopsychiatric defenses of antidepressants to justify their use after the final collapse of the "chemical imbalance" theory.

[LoveandLight]

Thanks CDAV..

[Cdav]

I'm currently taking 75 mg Lyrica, it seems to ease some symptoms. What is the difference between the way Lamotrigine and Lyrica act? Do they both act on GABA? Would Lyrica assist in healing like Lamotrigine, or just micro-doses of Lamotrigine might do this? 

[alwayslookup]

I just read up on Lyrica. It does look very similar to Lamotrigine. It also seems to be a "better" kind of anticonvulsant just like Lamotrigine is. 

Neither of them act directly on GABA like the benzos do. They act on GABA in indirect ways.

 

The main thing that both of them does is to temper CNS activity mostly by suppressing and tempering the glutaminergic system. (by blocking sodium channels, etc..)

 

I am no expert but it seems to me that Lamotrigine is more complex and sophisticated in it's mechanism of action. It also seems to have a better side effect profile. At least after comparing them after their wiki page (there is not a ton of info on Lyrica though ) 

 

So I guess Lyrica theoretically should help with the wd symptoms.

But we should wait for what Alto has to say about this....

 

(p.s. I am actually experimenting with low doses of Lamictal with promising results so far...it seems to be very useful.....it even seems to dampen some of the nasty benzo side effects and even some interdose wd symptoms...which is VERY cool.....probably and hopefully will help me to taper my benzo too

[Cdav]

Thank you Alwayslookup. 

 

I don't know if I can mix both together. Lyrica gives me relief from akathisia, paresthesia, anxiety and other sensations on head and body. I know it's masking the symptoms, not healing them, but it helps things be a bit more tolerable (sometimes it doesn't when symptoms are too strong). It does make me a bit dizzy and weak sometimes. 

 

I'm glad Lamictal is helping you, what dosage are you taking? 

[alwayslookup]

Not sure about mixing them. Wait for Alto's response on that....

 

Yes I think Lamictal indeed helps me. I only take around 3mg. Now I am starting to experiment with a bit more like 4mg. The effects might be mild but as far as I can tell it does help with the benzo side effects. It kind of dampens some of the nasty-ness of Klonopin (unpleasant sedation, interdose withdrawal symptoms like neuropathic pain, anxiety and weirdness). I do think it kind of clears my a head a bit too but I am still figuring it all out. But I do hope it will help me even more in the following months when I will start to taper my benzo. Now I am still changing when I took my doses of benzo etc. I do hope I can go higher with the Lamictal when my wd symptoms get worse....

[Altostrata]

Lyrica and lamotrigine are entirely different types of drugs. The only thing they have in common is that either may be prescribed for seizure disorders.

 

Yes, you can take them at the same time.

 

At the proper dosage, lamotrigine's beneficial effects in withdrawal syndrome are very subtle and gradual over time.

[Cdav]

Alto,

 

Thank you for your response. I'm going to give Lamotrigine a try again, but now I'll stick to a microdose. 

[Lexy]

Last year my doctor put me on 25mg to help effexor withdrawals. It was too activating for me. He told me to stop after 5 days.

Now I think I should have tried 5mg or less. What kinds of wds can lamo help with?

[Cdav]

Hi Lexy, I'm not sure, I hope it helps me with all my symptoms. Alto should be able to answer your question. 

 

 

My doctor finally agreed for me to try 5 mg lamictal, he gave me samples of 25 mg I'll be making a liquid form of it. 

[Altostrata]

Lamotrigine can calm the nervous system, particularly when you have alerting and sleeplessness.

 

Starting at a very low dose, far lower than 25mg, is described in great detail earlier in this topic. Please read a topic from the beginning before trying any remedy.

[Lilu]

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

Hi Alto,

 

This is very helpful and informative. I gave my new psychiatrist a whole bunch of articles to read on protracted withdrawal syndrome, which he never heard of. In fact he has never heard of any of the terms that I have used, which I have learned on this site. But unlike a lot of other shrinks, he is open minded. His comment was, "It doesn't say how to treat this!" So my question is, what literature can I give him that concisely explains how to treat protracted withdrawal.  Should I even bother trying to educate a clueless psychiatrist? At this point he actually admits that I need someone with psychopharmacology knowledge and that my illness is too complex for him to treat. He doesn't know what to prescribe. I am thinking of consulting a neuropsychiatrist instead.  

Either way, it would be really helpful to have some kind of manual or document that would explain protracted withdrawal and specify treatment, that one can give to open minded psychiatrists.

[Altostrata]

That's true, Lilu. Problem is, someone would have to write such a book.
 
Much of this site is about how to deal with protracted withdrawal syndrome.
 
See What is withdrawal syndrome?

The rule of 3KIS: Keep it simple. Keep it slow. Keep it stable.

 

The Windows and Waves Pattern of Recovery

 

You are probably better off working with your current psychiatrist. It is highly unlikely you will find one who understands withdrawal symptoms or protracted withdrawal syndrome.

[Hangingon]

Just found this topic... Would it work after coming off cocktail of ssri,snri, gabapentin, trazedone and gabapentin?

My WD hit hard AFTER completion of all tapers 8 months ago and I am in living hell

Reinstated Prozac 1 mg, quetiapine 6.25mgs but doc wants to increase quetiapine or reinstate fully on another ssri or increase Prozac because I am sooooo sick with withdrawal and barely functioning