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Seratonin directly affects the Immune System
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Prof Trevor Marshall
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 Posted: Fri Jan 30th, 2009 04:42

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For some time we have been noticing that the anti-psychotic drugs, including Prozac and Zoloft, seem to be affecting the immunopathology suffered by our members.

I have just noticed a paper "A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells"
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/107/3/1010
 
The paper was published in 2006, I am not sure why we missed it. But never mind...

Obviously the SSRIs, such as Prozac and Zoloft will act in this way. In fact, this study confirmed that Prozac blocked Seratonin uptake by lymphocytes in inflamed tissue.

I am currently thinking that much of the immunopathology arises from flow-down actions of the Th1 cytokines and chemokines in the adaptive immune system, so drugs which affect adaptive immunity are as interesting to me as drugs which affect innate immunity:)

As far as I know Klonopin is the only benzodiazepam which significantly interacts with the seratonin metabolism.  It is also affected by the CYP3A4 metabolism more than are the other benzos. I wonder whether there are any studies are out there yet which throw light on the reason why Klonopin causes so much trouble for our members, and why it is so hard to wean? Can somebody help me look for these?

..Trevor..
 

wrotek
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 Posted: Fri Jan 30th, 2009 05:28

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I have experience with only two benzodiazepines -  tetrazepam (Myolastan). It worked wonders, i felt normal on it and no after effects. i took it for muscle relaxations, prescribed by jaw surgeon, to relax skeletal muscles. 

Diazepam(valium), fror the other hand, did not work well all the time. First it was pleasant, then not.

Dunno why the difference.



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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 in low lux NoIRs 25D<7 Oct06
Sheila-Fl
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 Posted: Fri Jan 30th, 2009 10:02

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Klonopoin helps me to feel better when I use it but could it be the reason the my pain is so bad.  Would Xanax be OK.  I tried 2 1/2 Mg Diazapam last night and tried it once before.  Each time I had a terrible reaction.  Make my nervous system and pain much worse at time of use.   I just started phase 2 yesterday and I need to use something. What would be safe for MP.  :(  Sheila

 



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CFS,CFIDS,Fibromyalgia,MCS,IBS,IC,Thyroid Nodule Osteoarthritis,Malaise, start MP 11/05/08, 25D-39 11/15/08, 25D-30 01/09/09, 1,25D-47 01/09/09, Armour Thyroid, Ambien, Dry Eye Drops, Excedrin, Bio-Freeze, Affrin, Klonopin, Indoors most of time, NOIRS
Sheila-Fl
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 Posted: Fri Jan 30th, 2009 10:42

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Dr. Marshall, also wondering if a person has TH1 disease and is not on MP but uses any of above mentioned drugs will they have worse symptoms.  When I think back to 16 years ago when I had CFS and was not on any of the above drugs I had very little pain.  I started having panic attacks and then I went on the Klonopin and sometimes Xanax  instead of Klonopin and it seems that is when my pain started really manifesting.  I went 10 years with CFS and did not use the meds and had  very little pain.  :shock:    Sheila

 



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CFS,CFIDS,Fibromyalgia,MCS,IBS,IC,Thyroid Nodule Osteoarthritis,Malaise, start MP 11/05/08, 25D-39 11/15/08, 25D-30 01/09/09, 1,25D-47 01/09/09, Armour Thyroid, Ambien, Dry Eye Drops, Excedrin, Bio-Freeze, Affrin, Klonopin, Indoors most of time, NOIRS
Rico
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 Posted: Fri Jan 30th, 2009 11:47

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SSRIs form a subclass of serotonin uptake inhibitors, which includes other non-selective inhibitors as well. Serotonin-norepinephrine reuptake inhibitor, serotonin-noradrenaline-dopamine reuptake inhibitors and selective serotonin reuptake enhancers are also serotonergic antidepressants.



Venlafaxine (Effexor, Efexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class



Bupropion (INN, previously known as amfebutamone;[1] Wellbutrin, Zyban) is an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor



Is it possible, then, that antidepressants like Effexor or Wellbutrin also have similar issues? My wife has had a difficult time weaning from Effexor in particular.

Last edited on Fri Jan 30th, 2009 11:48 by Rico



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jlunn247
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 Posted: Fri Jan 30th, 2009 15:35

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Stronger meds on more specific receptors?
With immune suppressing abilities.
Do not tell the drug makers or they will have an excuse to re market the junk.

Last edited on Fri Jan 30th, 2009 15:40 by jlunn247



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Living in the land of the lost. JUST OLMECIP 5 x a day.Sarcoidosis Dx.
Bone disintegration,lungs,joint/muscle/stomach pain, diarrhea,incontinence. Weakness on my left side sweats,fatigue,neuropathy,headaches,mood swings,cognitive diss.
dgt
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 Posted: Fri Jan 30th, 2009 19:48

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Help! I don't know how to decipher all the big words at this time of night. I have tried twice since mid November to wean off of fluoxetine & both times felt it best to go back on so as not to carry on as a mad woman. I was hoping that my brain bugs had been sufficiently killed off to be able to function without the fluoxetine, but apparently not. Tell me whether continuing to take fluoxetine is slowing my recovery and what I can do if it is.

Dr. Marshall, do you ever take time to sleep????? You're amazing!

Thanks ever so much.

Just muddling through, Darlene



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Darlene postLyme RLS 1,25D47.3 Ph1May08 25D27.3Apr08 fluoxetine, NoIRs avoid outdoors/stay in shade/ zinc oxide Ph2July08 25D39 10/23/08 25D35 Ph3Nov08 11/10/08 25D32 1/27/09 25D20 began full z/m/c 3/6/09
Scottk
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 Posted: Fri Jan 30th, 2009 20:24

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at the onset of my symptoms,  but before diagnosis,  I occasionally took the recreational drug 'ecstacy'/MDMA. As far as I am aware ecstacy releases seretonin in the brain in a large amount. Once I became ill my symptoms were extremely aggravated upon taking ecstacy.

One of my most prominent early symptoms was uncontrollable laughter. Interestingly the only time I did not have this symptom was the day after taking ecstacy. Usually I would have nervous laughter from any interaction with people but the day after taking ecstacy, where the seretonin levels were very low, I felt emotionally very strong and did not have uncontrollable laughter. Some might say that with a seretonin depleted brain my propensity for laughter was simply diminished. On the other hand, the uncontrollable laughter, although I felt happy, did not come about because a situation was particularly funny. I  would therefore conclude that a low level of seretonin did in fact temporarily cure that particular symptom.



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Prof Trevor Marshall
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 Posted: Fri Jan 30th, 2009 20:54

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I work when I want to, sleep when I feel like it. Since Liz works nights and evenings several days a week, our household tends to follow a pretty atypical rhythm :)

I have no firm opinion on any of the various medications. When I look at the cohort I see results which are too variable to be dogmatic. One could focus on those with the most problems, who also tend to be taking the most medications and supplements, or one could look at people doing quite well with sleep meds, and even benzos. A decade ago, I myself never had any trouble with brand-name Diazepam occasionally, but certainly had bad reactions to other benzos. I think it all depends on the particular microbiota which one is saddled with.


ps: Nowadays I can take ten times the diazepam dose that used to make me warm and fuzzy (a decade ago) and it has essentially no effect  :):):) The human body is an amazing (and complex)  thing :):):)
 
 

Last edited on Fri Jan 30th, 2009 21:46 by Prof Trevor Marshall

dgt
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 Posted: Sat Jan 31st, 2009 11:04

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I do feel like I'm making progress (3 steps forward 1 step back). Early last year when my head was hurting constantly (before I began MP), I was also feeling very overwhelmed with work related issues so my PCP recommended I increase my Prozac to 20 mg. I had been on 10mg since 2002 and she felt maybe it was time for an increase. Fortunately, I requested double the amount of 10mg. caps instead of taking 20mg. caps so I could "experiment" with dosages. I found I felt better emotionally taking 10mg. in the morning and 10mg. in the evening. I was also taking Relora 200mg. 2-3x daily just to take the edge off. During the summer, after the school year ended (and I had begun Phase 1), I went back to 1 10mg. cap a day and remained at that dose until I began to try weaning from it in November. Oddly enough, in Dec. 1999 I had a hysterectomy and began taking estrace-first 1mg. then 2mg, then 3mg. I kept increasing (with my PCP's approval) because it took more to keep the symptoms down-especially feelings of sadness. That lasted until an unusual mammogram sent me to a breast surgeon who said I was increasing my risk of breast cancer (the estrogen was making my breast cells grow too fast-at least that's what I remember). So I went off estrace and endured the tortures of menopause and it wasn't until 2002 that I asked for some help with the depression (at that time, I had a new student who was autistic and running away and climbing on everything, as well as the news that my mom in Minnesota had been diagnosed with pancreatic cancer). Once I began to take the prozac and saw how it felt to have the bleak cloud lifted, I realized I probably should have started taking it a lot sooner! Anyway, the longer I'm on the MP, the farther back I can trace symptoms that indicate I was probably sick way before the tick bite in 1997.

If you find that there is a different antidepressant that might be better to use while on MP, I'm interested.

Thanks for always being on top of things.



____________________
Darlene postLyme RLS 1,25D47.3 Ph1May08 25D27.3Apr08 fluoxetine, NoIRs avoid outdoors/stay in shade/ zinc oxide Ph2July08 25D39 10/23/08 25D35 Ph3Nov08 11/10/08 25D32 1/27/09 25D20 began full z/m/c 3/6/09
jlunn247
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 Posted: Sat Jan 31st, 2009 14:09

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Too bad many people who self medicate usually have to stop suddenly because of concerns about health.
The mp has helped me wean from certain drugs but i still want to use nicotine
occasionally. Mostly cigarettes along with a caffeinated beverage. At least once a week.
When I feel normal.:?



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Living in the land of the lost. JUST OLMECIP 5 x a day.Sarcoidosis Dx.
Bone disintegration,lungs,joint/muscle/stomach pain, diarrhea,incontinence. Weakness on my left side sweats,fatigue,neuropathy,headaches,mood swings,cognitive diss.
jlunn247
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 Posted: Sat Jan 31st, 2009 15:43

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the risperidone i have tried sure interfered with my  IP. :(
 But it helped for a short while.
Maybe there is a palliative medicine for the MP that is fast acting
and not long lasting.



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Living in the land of the lost. JUST OLMECIP 5 x a day.Sarcoidosis Dx.
Bone disintegration,lungs,joint/muscle/stomach pain, diarrhea,incontinence. Weakness on my left side sweats,fatigue,neuropathy,headaches,mood swings,cognitive diss.
Lee
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 Posted: Sat Jan 31st, 2009 16:32

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I lately tried "Lyrica" and it did give me more energy and some pain relief before causing swelling in my ankles and achilles.  These are my prime granuloma spots and the original ones.  I have tried "valium" and it only works to help me sleep sounder.  This is ok though.  I also tried zanax and it too helped me to rest better but did not help me with pain control.  My only hope for pain relief now is with the hydrocodone and I have lately found I am not so sleepy on it. 



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MP-Feb05 ABX Breaks 7mth,18mth,3yr,5yr 2003 Sarc, Hyper-flex FM, Hashimotos, COPD, skin, joint pain and Glaucoma. 2014 blood work normal D-levels 4-5.
dgt
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 Posted: Sat Jan 31st, 2009 16:39

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I find that the 10mg. prozac works well. I discontinued the Relora at the suggestion of moderators and occasionally take a Valium in the evening. I was just concerned when I saw the post because I don't want to take anything that interferes with my recovery. I'm still hopeful that I'll eventually be able to discontinue the prozac. I just know that now is not the time. January through May is the busiest for me at school.



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Darlene postLyme RLS 1,25D47.3 Ph1May08 25D27.3Apr08 fluoxetine, NoIRs avoid outdoors/stay in shade/ zinc oxide Ph2July08 25D39 10/23/08 25D35 Ph3Nov08 11/10/08 25D32 1/27/09 25D20 began full z/m/c 3/6/09
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 Posted: Sun Feb 8th, 2009 14:11

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Not sure if this is of interest regarding this thread but I found it interesting as a lit review of the literature.

 

1: J Psychiatry Neurosci. 2009 Jan;34(1):4-20.

Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder.
Anisman H.
Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada. hanisman@ccs.carleton.ca

Activation of the inflammatory immune system provokes numerous neuroendocrine and neurotransmitter changes, many of which are similar to those provoked by physical or psychological stressors. These findings, among others, have led to the suggestion that the brain translates immune activation much as if it were a stressor. In this review, I provide synopses of the effects of traditional stressors on the release of corticotropin-releasing hormones at hypothalamic and extrahypothalamic sites, variations of serotonin and its receptors and changes of brain-derived neurotrophic factor (BDNF). These effects are similar to those elicited by activation of the inflammatory immune system, particularly the impact of the immune-signalling molecules interleukin-1 beta, interleukin-6, tumour necrosis factor-alpha and interferon-alpha on neuroendocrine, neurotransmitter and BDNF function. In addition, it is reported that stressors and cytokines may synergistically influence biological and behavioural processes and that these treatments may have long-term ramifications through the sensitization of processes associated with stress responses. Finally, I present an overview of the depressogenic actions of these cytokines in rodent models and in humans, and I provide provisional suggestions (and caveats) about the mechanisms by which cytokines and stressors might culminate in major depressive disorder.

PMID: 19125209 [PubMed - in process]

PMCID: PMC2612083



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MP Start June'08|CFS and FM diagnosed 1990| Severe relapse after florquinoline antibiotics 2007|Chronic lung congestion and infections|Graves Disease diagnosed 18 months into MP. Dec 2007, 1,25D=69 25D=26, latest 25D is Nov 12, d25=10.
dgt
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 Posted: Sun Feb 8th, 2009 14:43

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If I read the article right (which was difficult because it was so scientific!), depression can be brought on by an illness which causes the immune system to interact in some way with brain chemicals.....



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Darlene postLyme RLS 1,25D47.3 Ph1May08 25D27.3Apr08 fluoxetine, NoIRs avoid outdoors/stay in shade/ zinc oxide Ph2July08 25D39 10/23/08 25D35 Ph3Nov08 11/10/08 25D32 1/27/09 25D20 began full z/m/c 3/6/09
goyop
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 Posted: Fri Feb 13th, 2009 18:53

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As we are all learning, everything affects everything.  How profound I am!

So what to do when you are totally screwed up and nothing works right?  Thankfully, I found the MP which will hopefully actually deal with the root cause of most of my disease issues and other ongoing problems.

In the meantime I have suffered a systemic fungal infection which messed up everything in my body.  Followed by total exhaustion and burnout twice and wrapped up with sarcoidosis.  During all of this most every system in my body has been affected.  One of the chief complaints is disturbed sleep.  And of course anyone who is sick for a long time will eventually suffer from depression.  So again, what to do?

Occasionally, the Good Lord allows me to find a real doctor who is intelligent, thoughtful, wise, and doesn't think they are God.  One of those doctors has taught me to address each area in a methodical and sane way in the hope that if you can sleep a little better, be a little less depressed, be more awake in the daytime, etc, then the sum total will be a boost in well being.  And of course they all feed one another.

The MP is a whole other reality due to herxing and dosing and adjustments but we can still try to apply some salve to the different areas of suffering.  So for me, unless Dr. Marshall says that a certain antidepressant or sleeping remedy actually hinders the MP in a significant way then I proceed as usual.  The procedure is to research as much as possible, see what works for others (knowing that it may not be the same for you), find an expert in that field and try things.  It is all a crap shoot to find what works but worthwhile until you get to a better place when either you can do without it or reduce it.

During my time on the MP I have lowered and raised the various other drugs and my goal is to be free of them completely but we have to be patient and realistic.  Just wanting to be better does not make us better.  We will know when we are better.

Regarding some specific drugs, try not to stress too much.  There are just some drugs which are harder to stop taking.  Effexor is notorious for this. Clonopin is also a tough one to stop taking.  If you really need to stop taking it or are sure you don't need it, then just wean yourself gradually in steps and know that at the end you are going to feel bad for some days.  That is just the way it is.  (By the way 2.5 mg of clonopin is alot)

I have not done much research lately into these drugs but Prozac was never a very effective drug.  There are so many new and better drugs that you might consider.  Also, in my experience xanax is a bad drug.  It is super fast acting and strong but because of this it can turn nasty quickly.  Some like valium but others have no luck with it.  The point being do the research, get with a good MD, narrow it down on paper, then using much caution and prudence try things to see what helps you.

Good luck.

Joyful
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 Posted: Fri Feb 13th, 2009 20:44

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Greg, indeed...

Just wanting to be better does not make us better. We will know when we are better.
...profound you are! :)



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TikBitten
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 Posted: Fri Feb 13th, 2009 23:07

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Joyful wrote: Greg, indeed...

Just wanting to be better does not make us better. We will know when we are better.
...profound you are! :)


Ditto, that statement jumped out at me as well as soon as I read it. And, honestly, believing that is what probably keeps us all going...

TB

Last edited on Fri Feb 13th, 2009 23:26 by TikBitten



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Dx:Neurborreliosis 8/05|25D=46 1,25D=62 10/07|Avoid Sun&VitD since 10/07|Started Ph1&NoIRs 3/08|25D=18 3/08|25D=17 6/08|ModPh2 6/08|Ph2 9/08 stopped NoIRs|Ph3 1/09|25D=13 3/09|25D=10 5/09|25D=11 7/09|25D=15 9/09|25D=9 4/11
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 Posted: Mon Jul 13th, 2009 14:21

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Rico found...Bupropion (INN, previously known as amfebutamone;[1] Wellbutrin, Zyban) is an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor.
Wellbutrin is used for ADD as one of the issues is low dopamine leading to lack of focus, depression, etc.

I have a family member who finds it helps enough that if she forgets to take it she usually has a pretty difficult day.



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