• Announcements

Phil

N-acetylcysteine (NAC)

63 posts in this topic

Has anyone tried this during withdrawal? Does it help any symptoms? I've read about it on the other forum but have never got round to trying it, mostly because I'm scared of potentially feeling worse (I feel bad enough as it is).

I have some in my cupboard.

 

I wonder if it would help sleep or to reduce rumination, as I've read it is used for OCD. If it would help reduce some of my negative thoughts I'd be glad to try it.

Share this post


Link to post
Share on other sites

I never heard of it but can u tell us what it does?

Share this post


Link to post
Share on other sites

From the wiki on it:

 

"Psychiatry

 

Acetylcysteine has been shown to reduce the symptoms of both schizophrenia[21] and bipolar disorder[22] in two placebo controlled trials conducted at Melbourne University. It is thought to act via modulation of NMDA glutamate receptors or by increasing glutathione. Replicatory trials in bipolar disorder, schizophrenia and depression are underway."

I think it's supposed to help from its actions on glutamate, as supposedly glutamate is involved in withdrawal syndrome (see this post: http://survivingantidepressants.org/index.php?/topic/392-one-theory-of-antidepressant-withdrawal-syndrome/)

Share this post


Link to post
Share on other sites

N-Acetylcysteine aka acetylcysteine or NAC may help subdue the hyperactivity of the glutamate system that causes the withdrawal symptoms of insomnia, pseudo-anxiety, and pseudo-depression, excessive cortisol production and the awful sensations of autonomic dumping; also, the symptoms of OCD triggered in some of us by withdrawal.

 

I started looking at it to treat the eye inflammation I had in 2008 http://bastyrcenter.org/content/view/776/

NAC helps break down mucus, which might help me. It also contributes to the production of glutathione, the master anti-oxidant (although this is self-limiting).

 

I found there's a study going on at Yale by Christopher J Pittenger, MD, Ph.D. N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder http://clinicaltrials.gov/ct/show/NCT00539513?order=2%20:%20]http://clinicaltrials.gov/ct/show/NCT00539513?order=2

"...Existing medications for obsessive-compulsive disorder affect the neurotransmitters serotonin or dopamine; but increasing evidence suggests that functional disruptions of a different neurotransmitter, glutamate, may contribute to some cases of OCD. We are therefore interested in using medications that target glutamate as novel treatment options for those OCD patients who do not benefit from established treatments. One such medication is the drug N-Acetylcysteine, whose glutamatergic antagonistic properties may be effective in reducing the glutamatergic hyperactivity that is thought to contribute to the pathophysiology of OCD and MDD...." Citations for two papers by Dr. Pittenger are attached to the study proposal.

Edited by Altostrata
fixed text

Share this post


Link to post
Share on other sites

Also in 2008, I talked to a knowledgeable doctor about NAC. Dosage is an issue, and here's why (as he explained it): The glutamatergic and GABA systems are complementary. When they are in tune, everything works well. Glutamate is one of those things, like cortisol, where too little is bad and too much is bad but just right is just right. The system needs glutamic acid to produce the calming inhibitory neurotransmitter GABA and GABA regulates glutamate production.

 

If GABA is reduced, the glutamatergic system gets out of hand. If glutamate is too high, GABA is overwhelmed; if glutamate is reduced too much, inadequate GABA is produced. Any which way, you get symptoms of anxiety and agitation.

 

The right glutamategic-correcting dosage of NAC might even vary from person to person. This doctor knew exactly how NAC acted on the glutamate system and said its mode of action was different from lamotrigine and it might be complementary to Lamictal. My guess is it could be used to taper people off lamotrigine. It might also help benzo withdrawal, since an imbalance similar to antidepressant withdrawal is in place: too much glutamate. In benzo withdrawal, it is due to downregulation of GABA; in antidepressant withdrawal, downregulation of serotonin.

Edited by Altostrata
fixed text

Share this post


Link to post
Share on other sites

NAC appears to have a number of therapeutic effects; one of them to break up excessive mucus. When used for eyelid inflammation, the dosage is 100mg three times a day. (And this is the normal NAC, with a half-life of 1.5 hours.) What is does is change the composition of eye lubrication so it doesn't tend to form an irritating crust. This indicates to me the lower dosage is sufficient for systemic effects -- it gets all the way into tear production.

 

It looks like the most common dosages available are 500mg-600mg tabs or caps.

 

This is what my experience with NAC was in September 2008: I chose to try the Jarrow sustained release dosage; the tablets are 600mg. The Jarrow tabs are in two layers. I wrote Jarrow and found the wider layer, 400mg of the 600mg tablet, is the sustained-release NAC. Cutting up the tablet does not affect the sustained-release part.

 

I cut the 600mg tab into quarters; the layers separated. I took 1/4, approximately 150mg, on an empty stomach with fruit juice. My experience was mixed. Being hypersensitive, I believe I can fairly accurately tell what something does. At first, I felt energized and calm, so pretty good there. I had lunch. Later in the day, the sustained-release part kicked in, majorly upset my stomach, and increased anxiety. The unpleasant part lasted for many hours. I could barely eat dinner. I had as close to an anxiety attack as I've had in 8 months.

 

Fortunately, I was able to sleep some anyway and the next day I feel okay. All together, I felt the effects for 12 hours. This makes sense because the sustained-release part is supposed to increase NAC half-life in the small intestine from 1.5 hours to 4 hours. Adding the normal-release component, this sums up to a half-life of maybe 5.5 hours and more than 10 hours to be out of the bloodstream completely. (I have no doubt that the Jarrow product is sustained-release -- I had effects from their NAC-Sustain for 12 hours.)

 

My interpretation of what happened fits the glutamate-GABA model. When the sustained-release part kicked in, the dosage of NAC was too much for me and lowered my glutamate too much. This left the GABA system with not enough glutamic acid to work with, raising anxiety. (And the stomach distress didn't help, either.)

 

I conclude that NAC probably does lower glutamate production, which is a good thing for people suffering from anxiety, but it is quite powerful. Figuring out dosage could be challenging. If you are suffering from anxiety, start with a very small dose of the normal-release NAC in the morning, which will limit unpleasant effects, if any, to a few hours. To try this again, I'd just take a quarter of the 200mg normal-release layer.

 

My hypothesis is that minimal dosages of NAC may be enough to temper the glutamatergic system and reduce anxiety. Large sustained-release doses may not be necessary for this purpose. This is another one of those things where more is not better.

 

----------------------

I've been giving NAC (n-acetyl cysteine) a try for about a week, and so far the results are promising. Dosage is tricky. I cut up the Jarrow tablets and have been taking 50mg of the regular-release NAC in mid-morning on an empty stomach. Even when I feel really crummy, I find it makes me feel calm and happy for a few hours (half-life is 1.5 hours). (I am not having rushes of anxiety any more, but I often feel lousy from too little sleep.)

 

Yesterday I took 50mg at 11 a.m. and again at 4 p.m. and it seemed to work both times. But, toward evening, I started to feel a little buzzy, so it might have been too much. Fortunately, it did not seem to interfere with sleep; I slept a little better last night. I am thinking this might be a good thing to take when I wake up at 2 a.m. It might help me get back to sleep. (Also, it seems to have helped my eye inflammation.)

 

----------------------

My experience with NAC as so far been good. The thing is, I can only take 50mg at a time because, taken on an empty stomach, 100mg seems to cause upset, even when it's extended-release. While I've had okay results with NAC during the day, it's not going to work for me when I wake up -- I get an upset stomach even when I take 50mg in the middle of the night. For me, it needs some food around it to cushion it.

 

Talked to the knowledgeable doctor about NAC at night and he said something really interesting. Seems that when the body is doing its repair work during deep sleep, it works best in an environment without additional antioxidants as they interfere with the repairs. He said NAC in the early part of the night would be fine.

 

Remember the paradoxical character of the alerting reaction: if you go after it too aggressively, you will set it off. Starting with very low doses and slowly titrating up is the way to go.

Edited by Altostrata
fixed text

Share this post


Link to post
Share on other sites

The following is a little chewy but seems to explain the calming effects of NAC (H2S is hydrogen sulfide): "...The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant...."

 

Nutr Rev. 2004 Sep;62(9):348-53.

 

New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant.

 

Dominy JE, Stipanuk MH.

 

Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.

 

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/15497768?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

The enzymes of the transsulfuration pathway also have the capacity to catalyze the desulfhydration of cysteine. Recent studies demonstrate a role of the transsulfuration enzymes, cystathionine gamma-lyase and cystathionine beta-synthase, in catalyzing the desulfhydration of cysteine in brain and smooth muscle. The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation.

Share this post


Link to post
Share on other sites

I am bumping this for any updates?

I am interested in maybe trying this for anxiety and ruminating anxious thoughts.... to have in my tool box

Share this post


Link to post
Share on other sites

just to share...I've taken NAC off and on for several years now...I don't FEEL anything but I have felt it may help foundational well-being...

 

I now take long breaks between periods of taking it because I talked to a interesting and knowledgable psychiatrist who said it messes really badly with mucous production which has all sorts of broad implications but bottom line she didn't know how serious that might be and so caution is warranted...

 

the times I take it now is when I take tylenol which grossly depletes ones body of glutathione...so if and when I take tylenol I will take NAC for a few days to hopefully get my glutathione back on track...

 

sorry, I don't have documentation for these statements...you'll have to use google if you need that!!

Share this post


Link to post
Share on other sites

Thanks Gia!

 

Any one else?

Share this post


Link to post
Share on other sites

Hi, Peggy: this supplement was one of many I took when I was withdrawing from remeron. I had no knowledge of any paradoxical effects for these supplements since I was under the care of my integrative doctor and he prescribed according to the supplement company. I did finally quit it because it was making my already volatile anxiety even worse, a lot worse. I did notice after I quit it that it contains a sulfa component. I was always wondering about the color of the material. It definitely is orange. Long story short, I've had a sulfa allergy my whole life.

 

I wasn't sure that was the reason for the reaction I had to it. I had reactions to just about any supplement that was offered to me. That could be the reason why I am still very miserable nearly a year after remeron withdrawal. My brain may be reeling from a compound exposure to all these supplements plus 12 years of remeron.

 

Be very careful. It sounds like alto had some pretty thoughtful experience with it.

Share this post


Link to post
Share on other sites

I've been taking NAC for a few years to support glutathione production, because of chemical sensitivities. I take a supplement that provides 200 mg at a time. I usually take it with lunch before I go to work, and at work I'm usually bombarded with stimuli so not really tuned in to my subtle intrapersonal reactions and sensations. I've never noticed any obvious effect from the NAC. That doesn't mean it's not doing anything, though.

 

The supplement I use has 200 mg of NAC along with a few other things.

Share this post


Link to post
Share on other sites

"In glutamatergic neurons, the production of H2S by cystathionine beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. "

 

Wouldn't that be stimulating?

 

It's so tricky trying to tweak body chemistry. I'm tempted to just quit all supplements altogether.

 

But not yet, because I see that NAC is water soluble, which means Fun With Liquids for Rhiannon! So I mixed up some 600 mg capsules that have been sitting in my closet since I tried them and decided 600 mg was too strong. Now I have a 6 mg/mL solution of NAC and I can play with that and see what effect if any it has on my anxiety and stimulation. Heh heh heh...mad scientist...love my pipettes...

Share this post


Link to post
Share on other sites

How weird!! This is the second supplement (the other being l-arginine) that is up for discussion in Symptoms and self-care and which I am coincidentally taking for another reason entirely (fertile cervical mucus to try to get pregnant). (So what GiaK says about mucus production really makes sense! Boy, does it work.)

 

I'm mention here again that I first started taking FertileCM (containing both NAC and l-arginine, but it doesn't disclose the amounts of each) in March/April, and I had a definite period of improvement. I had attributed it to the panax ginseng I was also taking. I'm taking FertileCM AND ginseng both now, though, and am doing awful (then again, maybe I'd be worse if I wasn't taking them!).

 

Like Rhi, I'm tempted to quit all supplements also. I actually did for the the three weeks I was on vacation, and I was the best I've ever been for the first couple of weeks. Next to zero anxiety, zero depression, and incredible sleep. I still tired easily and was really exhausted all the time, but it was so great to be able to sleep naps and sleep in... on a few days I slept 8 to 9 hours straight without waking up! Maybe it's a good idea to quit supplements once in a while? Or perhaps removal of all stress for a while overrides just about anything else!

Share this post


Link to post
Share on other sites

i took the NAC faithfully for a few months - i was taking 1000mg in the morning. Can't say i noticed anything either way - good or bad, but i have just decided to recommence. I will break the tablets up to start so i don't start with 1000mg outright. My psych doc recommended i take it - she had me on 1000mg daily for a month then up to 2000mg daily. I don't seem to be overly sensitive to medications - with the exception of reducing effexor :lol:

Share this post


Link to post
Share on other sites

I started taking it because I read that it has anti-oxidant benefits that help damage caused by stress and that it is a precursor to an amino acid that fights depression. I haven't started my taper yet, but since taking NAC, I seem to have more energy and motivation, which is symptom relief I never got from an antidepressant. I also take lots of omega-3.

 

What do others think? Have you had any other success with supplements?

Share this post


Link to post
Share on other sites

I started taking it because I read that it has anti-oxidant benefits that help damage caused by stress and that it is a precursor to an amino acid that fights depression. I haven't started my taper yet, but since taking NAC, I seem to have more energy and motivation, which is symptom relief I never got from an antidepressant. I also take lots of omega-3.

 

What do others think? Have you had any other success with supplements?

 

Hi Finn,

 

I am glad NAC is working for you.

 

I have thought about taking it because it is supposed to be helpful in fighting the affects of sleep apnea. But because I have had reactions to so called harmless supplements, I am very reluctant to take it.

 

I have had the best luck with fish oil, cal/mag, cod liver/butter oil.

 

CS

Share this post


Link to post
Share on other sites

In case anyone else is also unfamiliar with NAC, posting link to brief article by Emily Deans, MD, in Psychology Today:

http://m.psychologytoday.com/blog/evolutionary-psychiatry/201201/problems-i-have-nac

 

Tangentially, I found this statement very disturbing:

 

"As a specialist I am required by medical convention to stick to the brain and keep my little nose out of other parts of the body... but NAC has some interesting properties in the noggin as well."

 

Therein lies the problem with medicine.

Share this post


Link to post
Share on other sites

In case anyone else is also unfamiliar with NAC, posting link to brief article by Emily Deans, MD, in Psychology Today:

http://m.psychologytoday.com/blog/evolutionary-psychiatry/201201/problems-i-have-nac

 

Tangentially, I found this statement very disturbing:

 

"As a specialist I am required by medical convention to stick to the brain and keep my little nose out of other parts of the body... but NAC has some interesting properties in the noggin as well."

 

Therein lies the problem with medicine.

 

That is funny, they are allowed to prescribe drugs off label when there is no evidence they work but they are not allowed to mention supplements that might be helpful. Yup, medicine has a problem.

 

CS

Share this post


Link to post
Share on other sites

 

In case anyone else is also unfamiliar with NAC, posting link to brief article by Emily Deans, MD, in Psychology Today:

http://m.psychologytoday.com/blog/evolutionary-psychiatry/201201/problems-i-have-nac

 

Tangentially, I found this statement very disturbing:

 

"As a specialist I am required by medical convention to stick to the brain and keep my little nose out of other parts of the body... but NAC has some interesting properties in the noggin as well."

 

Therein lies the problem with medicine.

 

That is funny, they are allowed to prescribe drugs off label when there is no evidence they work but they are not allowed to mention supplements that might be helpful. Yup, medicine has a problem.

 

Nor *allowed* by medical convention to address how drugs they use (for given specialty / body part) effect the rest of the body...is how I read it. How many times we've been dismissed because doctors think psychotropic drugs don't effect anything below the neck..? When did the brain cease to control the body??

 

Ok, off my soapbox!

Share this post


Link to post
Share on other sites

It's probably best to avoid supplements when tapering off of antidepressants, especially stimulating ones. The only ones that seem to be almost universally helpful are high quality fish oil and magnesium, and a few people here have found that even the fish oil is too stimulating. Right now your mind and body are numbed to some extent from Effexor, but once you begin tapering it will likely be a different story. People who taper off of antidepressants generally find that many things that had never bothered them before will be over-stimulating during withdrawal.

Share this post


Link to post
Share on other sites

 

 

In case anyone else is also unfamiliar with NAC, posting link to brief article by Emily Deans, MD, in Psychology Today:

http://m.psychologytoday.com/blog/evolutionary-psychiatry/201201/problems-i-have-nac

 

Tangentially, I found this statement very disturbing:

 

"As a specialist I am required by medical convention to stick to the brain and keep my little nose out of other parts of the body... but NAC has some interesting properties in the noggin as well."

 

Therein lies the problem with medicine.

 

That is funny, they are allowed to prescribe drugs off label when there is no evidence they work but they are not allowed to mention supplements that might be helpful. Yup, medicine has a problem.

 

Nor *allowed* by medical convention to address how drugs they use (for given specialty / body part) effect the rest of the body...is how I read it. How many times we've been dismissed because doctors think psychotropic drugs don't effect anything below the neck..? When did the brain cease to control the body??

 

Ok, off my soapbox!

 

Nah, don't leave :lol:

 

Great point as ironically we keep hearing the propaganda that you can't separate the brain from the rest of the body. But yet, when it suits the purpose of psychiatry, it is ok to do that.

 

CS

Share this post


Link to post
Share on other sites

Thanks for your posts. I'm in an exceptionally bad mind space right now and felt guilty all night for shanghaiing the NAC topic.

Share this post


Link to post
Share on other sites

Thanks for your posts. I'm in an exceptionally bad mind space right now and felt guilty all night for shanghaiing the NAC topic.

 

I am sorry to hear that Barb and hope things improve.

 

CS

Share this post


Link to post
Share on other sites

Thanks for your posts. I'm in an exceptionally bad mind space right now and felt guilty all night for shanghaiing the NAC topic.

 

Hugs to you. I hope you feel better soon. We're here to listen and not judge.

Share this post


Link to post
Share on other sites

Thanks for integrating my posts with the other information on the supplement. I found the dosing information very helpful. I was actually taking 3 of the 600mg pills daily, which I now understand might be way too much. But in the research studies, they were using around 2000mg, which is approximately 3 x 600mg. Long story short, I am very agitated! I will cut down to one a day, though, especially as I start tapering and trying to stabilize what I put into my body.

Share this post


Link to post
Share on other sites

I don't know how they managed to get 2000mg NAC into those people in the study. It sure didn't agree with me.

Share this post


Link to post
Share on other sites

It must just be an individual difference thing. Some people can stomach more without stomach upset. For the study, they probably eliminated all the people who couldn't handle the dose. Personally, it never bugged my stomach at all, even when I took two 600mg pills at once.

Share this post


Link to post
Share on other sites

I believe it can be helpful if you can tolerate it.

Share this post


Link to post
Share on other sites

Question for those who have or are taking it currently: What brand are you using? I recently read that it can lose its strength because it quickly oxidizes when it touches air during production. I'm using the Vitamin Shoppe brand. I wonder what kind of quality is it. Apparently there's PharmaNac, which is the highest quality available, but it is much more expensive. Is it worth paying more?

Share this post


Link to post
Share on other sites

Question for those who have or are taking it currently: What brand are you using? I recently read that it can lose its strength because it quickly oxidizes when it touches air during production. I'm using the Vitamin Shoppe brand. I wonder what kind of quality is it. Apparently there's PharmaNac, which is the highest quality available, but it is much more expensive. Is it worth paying more?

 

Interesting question. I am taking NAC on a physicians recommendation. I am taking a fairly expensive brand, pure encapsulations. In my case my doctor advocates for that brand because it's hypoallergenic.

 

I haven't heard of about those oxidation issues though. I think if you're feeling a positive effect from the Vitamin Shoppe brand, I'd finish the supply and consider how beneficial you estimate the NAC has been before shelling out more $.

 

Alex

Share this post


Link to post
Share on other sites

I thought I should let people know that NAC has been only the thing that has made my severe case of SSRI neurotoxity (I follow Shipko in calling it this rather than withdrawal, for reasons that also have to do with my experience) livable over the last 6 months.  It's been over 3 years since I quit Wellbutrin and Celexa cold turkey, and I am still nowhere close to normal, but a high dose of NAC has delivered serious improvements.  I have been on about 3000mg a day (split day and night).  I should say that like most here, I am still hypersensitive to almost all drugs (I have tried almost everything, much of it for the year before I became aware that this all stemmed from use and discontinuation of antidepressants).  I was on a small dose of lamotrigine for a long time, and this had no impact.  I took 600 mg of NAC for almost a year, which did nothing, and on a lark I went up on it and then kept going up, with no real side effects.

 

My experience tracks with much of what others report here, and with Alto's categorizations of these problems.  I had extreme insomnia and anxiety for about a year, but my biggest persisting problems have been cognitive and emotional, and, until recently, severe headache-like apin and full body neuropathic burning.  My ability to read, to process, to remember, to pay attention, to connect cognitively and emotionally to any experience, no matter how ordinary, were severely compromised.  I had a full neuropsych workup 18 months ago to try understand (and, in some sense, objectively validate) these problems, and the testing showed serious, in places technically "severe" impairments, especially in the domains of memory, attention, and visuo-spatial processing, impairments inconsistent with what can be established as baseline or overall intelligence.  I would have unquestionably lost my job had I not been, strangely enough, a college professor, where I could (and did) take partial medical leave, and then teach classes with texts I was had taught before and did not have to re-read, classes that were discussion rather than lecture based.  I called somebody on this site "silver star" a year ago because I could not process the page clearly enough to understand that this was not someone's moniker.

 

The NAC has muted much of the head and body discomfort.  It has helped me regain a certain level of mental clarity---I can read and pay attention to things much better.  It has also stabilized my mood.  I was suicidal for many periods of the first 2 years after discontinuation---having never had anything approaching a suicidal thought my entire life---but those thoughts and feelings have been entirely eliminated.  I confess that it has, it seems, muted even further my already devasted libido and sexual function.  (This is one area where I have not ever seen any improvement.)  It also, strangely, has created muscle problems when I do athletics, not so much weakness as terribly soreness, even when the muscles have been regularly used.  But it has helped me go from perhaps 30% normality to 60-70% normality, especially in the domains of cognition and pain.

 

I think that SSRI neurotoxity is perhaps more various than is sometimes suggested here, and of course everyone is different, so I don't know if this would work for others.  And I don't know if I would have been able to tolerate such a dose in the first year or two of my withdrawal.  I have never, it may be worth noting, had any of those symptoms characterized as "autonomic dysfunction" on this site.  No digestive, temperature, blood pressure, etc. kinds of problems.  And my hypersensitivity to drugs has always been exactly the same: the exacerbation of the horrible pressure in the head and the tremulous, neuropathic burning in my body.  No nausea, etc. 

 

Anyway, thought I would post this in case NAC might help others.  My best to all.

Share this post


Link to post
Share on other sites

Good to hear from you, Binx, and good to hear NAC has been helpful.

I agree, autonomic dysfunction is highly various. The autonomic nervous system controls so many functions, the permutations are endless.

Don't worry about the "silver star" error -- many make it! It takes a bit to get used to the layout of the posts.

The neuropathic pain is an autonomic symptom (fibromyalgia is also thought to have an autonomic component). I had it for about 1.5 years in my hands, arms, and shoulders. It seemed to resolve with acupuncture.

The autonomic nervous system controls muscle tension, blood vessel dilation, nerve conduction and other subtle operations that might be the source of your neuropathic pain. Inflammation might also be involved (did you get tested for this?)

NAC is a precursor of glutathione http://www.jissn.com/content/2/2/38
Glutathione is involved in many immune system cell repair functions. (It's sometimes called an antioxidant, but that doesn't explain everything it does.)

From the paper abstract at http://www.sciencedirect.com/science/article/pii/S0163725813001952

N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l-cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug conjugation. Other therapeutic uses of NAC have also emerged, including the alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated disruption of disulfide cross-bridges in the glycoprotein matrix in mucus.

....
This review seeks to re-evaluate the mechanism of action of NAC as a precursor for GSH synthesis in the context of its activity as an “antioxidant”. Results from recent studies are examined to establish whether the pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion and the presence of functional metabolic pathways for conversion of NAC to GSH) have received adequate consideration in the interpretation of the data. A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.

 
Curr Opin Pharmacol. 2007 Aug;7(4):355-9. Epub 2007 Jun 29.
N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency.
Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA.

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/17602868 Full text at http://www.mediafire.com/view/3tyroedsbc6f6bf/07_Atkuri_n-acetylcysteiine.pdf

Glutathione (GSH) deficiency is associated with numerous pathological conditions. Administration of N-acetylcysteine (NAC), a cysteine prodrug, replenishes intracellular GSH levels. NAC, best known for its ability to counter acetaminophen toxicity, is a safe, well-tolerated antidote for cysteine/GSH deficiency. NAC has been used successfully to treat GSH deficiency in a wide range of infections, genetic defects and metabolic disorders, including HIV infection and COPD. Over two-thirds of 46 placebo-controlled clinical trials with orally administered NAC have indicated beneficial effects of NAC measured either as trial endpoints or as general measures of improvement in quality of life and well-being of the patients.

Mark Hyman's opinion
Glutathione: The Mother of All Antioxidants
http://www.huffingtonpost.com/dr-mark-hyman/glutathione-the-mother-of_b_530494.html
 
Whey protein isolate also boosts glutathione production. Both NAC and whey protein isolate are often recommended for chronic fatigue syndrome, another mysterious condition with an autonomic component, the symptoms of which overlap with withdrawal syndrome. See paper at http://www.ncbi.nlm.nih.gov/pubmed/11703165

 

 

I have no idea if your benefit from NAC is because of the glutathione connection or something else. These reactions are so complex. But whatever works, works, and thanks for telling us about this.

 

...I did notice after I quit it that it contains a sulfa component. I was always wondering about the color of the material. It definitely is orange. Long story short, I've had a sulfa allergy my whole life. I wasn't sure that was the reason for the reaction I had to it.....

 

NAC does NOT contain sulfa; it is a sulfur compound -- sulfa and sulfur are entirely different!

Share this post


Link to post
Share on other sites

It also modulates the glutamate system: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044191/

 

So it may lend credence to your glutamate theory of withdrawal.  Though lamotrigine did absolutely nothing for me. 

 

Neuropathic pain is the closest description I can get to what I've experienced, though I'm not sure it's technically correct.  Never any tenderness to the touch, and the sensation is evenly distributed across the entire body.  It's like a painful internal shaking---thus the whole akathisia/agitation question---but it's not really agitation.  It has no mental component; it doesn't track with mental states at all.  It's even more prominent, for instance, when I'm sleepy and groggy when I get up to go to the bathroom in the middle of the night.  It doesn't make me feel agitated, just uncomfortable (when it was at its worst, intolerably uncomfortable).  I tried everything for it.  Low Dose Naltrexone actually helped for about 2 months, but then stopped working entirely.  I even tried ketamine infusions, because these have seemed to work for people with intractable neuropathic pain (I was desperate).  They actually made the problem worse, though they did lift my mood significantly.  Nothing else that helps people with non-drug induced neuropathic pain (alpha-lipoic acid, etc. helped at all).  I did 6 sessions of acupuncture, but it actually aggravated it as well.  Since the NAC, the internal tremulousness is still there, but no longer painful, if that makes sense.

 

When you say get tested for inflammation, what do you mean?  I had a spinal tap 18 months ago, but was told I didn't have any classic inflammatory markers.  They found West Nile Virus antibodies, which moved some doctors, including an infectious disease guy, to suggest that I had had some sort of milder encephalitic reaction to WNV.  But from what I can tell the pathology of WN encephalitis looks different from anything I presented.  I had an EMG that didn't show any technical neuropathies, but did show some sort of muscle abormaliites.  I was never given a clear explanation, but I was told it couldn't be a central neurological issue.

 

One reason the autonomic dysfunction account seems incomplete in my case is the issue of cognitive impairment.  The cognitive problems are not mood-based---they have nothing to do with anxiety or depression or the "artificial" creation of these states in withdrawal (the neuro-psych testing validated what I already knew to be true).  I don't understand human physiology as well as you do, and probably don't understand the full scope of the autonomic nervous system, but it's unclear to me how, say, disorders of visuo-spatial processing could be related to the ANS. 

 

This is another reason why it seems sensible to speak of neurotoxicity.  It's also become clearer to me, looking back, that many of the problems that became full blown after discontinuation began before I stopped the meds.  My hypersensitivity to medications and supplements, for instance, was already visible while I was on Celexa.  I remember, at different times, trying to take B vitamins for energy while on the medication, and having insane agitation and shakiness, even at modest doses.  The same thing happened when I tried to take certain stimulating supplements for SSRI sexual disfunction, like Yohimbe and Maca.  My standard 2 cups of coffee in the morning also began to make me feel strangely uncomfortable, different from the normal "jitters" of caffeine intake.  I never had any problems with vitamins or supplements or caffeine before I started taking Celexa.  At the time I just thought, "that's weird,"---I didn't connect it to the drug at all.  Of course, this was nothing compared to the hypersensitivity after withdrawal, but it suggests some sort of pathological process that can't be completely explained as withdrawal.

 

Anyway, just some thoughts.

Share this post


Link to post
Share on other sites

Others experiencing withdrawal syndrome have described the same symptoms. They are not unknown here. Your pattern is not atypical.

 

No one else has had any success with the usual treatments for neuropathic pain, either. It's too bad acupuncture didn't work for you; I found it helpful -- but the practitioner needed to be reminded that aggressive treatment would result in a paradoxical reaction. He was very knowledgeable, though, and found ways to treat that I guess were more indirect.

 

Interesting these internal vibrations become more intense at night. Potassium, an electrolyte, is at its lowest in the middle of the night. You may try a little potassium supplementation at night. Are you taking fish oil and magnesium?

 

see
http://survivingantidepressants.org/index.php?/topic/36-king-of-supplements-omega-3-fatty-acids-fish-oil/
http://survivingantidepressants.org/index.php?/topic/1300-magnesium-natures-calcium-channel-blocker/

 

It sounds to me like Celexa was always excessively stimulating for you. This may have incurred underlying dysregulation that made you susceptible to withdrawal syndrome. Whatever the mechanics, recovery is the same.
 

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!


Register a new account

Sign in

Already have an account? Sign in here.


Sign In Now