Is it possible we are suffering from some form of inflammation?

Could it be that our Central Nervous Systems are inflamed and that is the reason for our various symptoms?  Also, the things that help me are things that naturally reduce inflammation like the keto diet, supplements like fish oil that I take, and exercise.  Also, I have recently been prescribed an anti-inflammatory medication for a problem I have with my knee.  I don't like taking any kind of medication so I have resisted taking them.  But I did take one today and I noticed that my symptoms decreased substantially.  I'm interested in hearing what you guys think. 

Keto diet reduces glutamate, fish oil helps nerve remyelination. Inflamation increases glutamate in the body.

I agree there must be a connection, I have an inflammation issue as well.

Have you had your C-Reactive Protein level checked (i.e. in a blood test)? It's a reflection of systemic inflammation. Mine is low and has been low for quite some time, so in my case, I would say, no, inflammation is not the cause of what's happening to me.

 

Here's the Mayo Clinic info on C-Reactive Protein:

 

https://www.mayoclinic.org/tests-procedures/c-reactive-protein-test/about/pac-20385228 

Could it be that our Central Nervous Systems are inflamed and that is the reason for our various symptoms?  Also, the things that help me are things that naturally reduce inflammation like the keto diet, supplements like fish oil that I take, and exercise.  Also, I have recently been prescribed an anti-inflammatory medication for a problem I have with my knee.  I don't like taking any kind of medication so I have resisted taking them.  But I did take one today and I noticed that my symptoms decreased substantially.  I'm interested in hearing what you guys think.

Hi,

Yes, in part.  Immune factors and cytokines are very potent neuromodulators. And there are lots of different cytokines.

For example, NSAIDs in some studies have shown to have a statistically significant effect on neuropsychiatric disorders like depression (you can google the studies and find them easily) through this pathway

 

 

For PWS:

There’s a significant question as to cause and effect in the case of PWS, for example.  Is the immune system cytokine profile off kilter because of the protracted stress on the body, from PWS, and is that merely aggravating the PWS, or is the PWS onset itself caused by a disordered cytokine profile in those that have PWS?

 

Also there’s the greater question of the cross correlation of symptoms between extremely complex syndromes like CFS and fibromyalgia, for example, and the neurophysiology of PWS.

 

For example, benzos alleviate CFS symptoms in some patients, because the underlying neurophysiology of the CFS in these patents is biased toward hyperexcitability and this could be due in part to this irregular cytokine profile( this is as opposed to the other subset of CFS patients that are neurophysiologically biased in the opposite direction.  This might explain why benzos don’t help in all CFS patients)

 

The cytokines as neuromodulators is a very interesting area of study.

 

 

-cs123

In my case, NSAIDs weren't helpful at all. I had to take them because I fractured my foot from the dizziness (i.e. which was caused by benzos and SSRIs), and the pain was insane. Trying to walk on a fractured foot when dizzy is pretty horrific. And I couldn't wear the fracture boot due to the dizziness.

Anyway, NSAIDs can cause or worsen tinnitus (lots of info available on this), which I already had. And they certainly didn't help the dizziness.

 

It would seem to me that benefits from NSAIDs would be rather symptom-specific. Maybe some could be helped, but they would need to be aware of the associated risks of these meds (including tinnitus and gastrointestinal issues).

In my case, NSAIDs weren't helpful at all. I had to take them because I fractured my foot from the dizziness (i.e. which was caused by benzos and SSRIs), and the pain was insane. Trying to walk on a fractured foot when dizzy is pretty horrific. And I couldn't wear the fracture boot due to the dizziness.

Anyway, NSAIDs can cause or worsen tinnitus (lots of info available on this), which I already had. And they certainly didn't help the dizziness.

 

It would seem to me that benefits from NSAIDs would be rather symptom-specific. Maybe some could be helped, but they would need to be aware of the associated risks of these meds (including tinnitus and gastrointestinal issues).

 

I agree Lapis. Anecdotally,  I don’t feel right with ibuprofen, but aspirin is fine.

 

There’s another significant pathway to consider in this respect, the eicosanoid pathway (COX, TXAs, PGHs, etc)  Eicosanoids are directly modulated by NSAIDS, as you know

 

Eicosanoids are also neuromodulators (google it, there’s some research in this area, but not as much as cytokines as neuromodulators)

Since ibuprofen acts differently than aspirin in regards to this, this might be why one affects a person differently than the other in terms of neuro.

 

There is so many things to consider when trying to analyze inflammation and the immune system in regards to neurophysiology.....

Right....and everyone seems to have such a different symptom profile. There's a ton of variation. And genetics must play a huge role in all of this.

 

I'm in the midst of reading another study that acknowledges the long-term negative effects of benzos, as well as the interactions between them and antidepressants, which I also took. Those who have taken multiple meds are likely dealing with a more complicated picture than those who took only one type of medication.

Here's the study I mentioned: "Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology" . There's a section on the "Neurobiological effects of chronic benzodiazepines". Well worth checking out.

 

https://sci-hub.tw/https://www.researchgate.net/publication/341688809_Understanding_the_effects_of_chronic_benzodiazepine_use_in_depression_a_focus_on_neuropharmacology

 

 

 

The NSAID that I was prescribed is called Etodolac.  https://en.wikipedia.org/wiki/Etodolac

 

It worked so well in reducing my symptoms that I'm afraid of taking it because I have a deep suspicion that it is fools gold and that it is giving me short term benefits in exchange for prolonging my healing.  I'm very wary of taking any medications at all.  The pain from head aches and other things has to be unbearable before I even consider taking an advil. 

Here's the study I mentioned: "Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology" . There's a section on the "Neurobiological effects of chronic benzodiazepines". Well worth checking out.

 

https://sci-hub.tw/https://www.researchgate.net/publication/341688809_Understanding_the_effects_of_chronic_benzodiazepine_use_in_depression_a_focus_on_neuropharmacology

 

Thanks Lapis

It’s a good article

 

 

I agree that antidepressants + benzos complicate the picture a lot

 

As the article states, the rigorous combination testing is horribly lacking (yet they are liberally and routinely prescribed in this manner)

 

The benzo neurogenesis angle is something that I had written about last year, and I believe what they are getting at, because adult neurogenesis is highly dependent on a properly functioning GABAergic system.  There’s tons of good research in this area.

 

As the article states, the acute vs. chronic effects of benzos are, in general, polar opposites, across a variety of systems.(See figure 1).

 

If we add voltage gated CCs, NOS, and immune system effects to figure 1,  that’s a good model.  It’s a very tangled web.

 

-cs123

 

 

Here's the study I mentioned: "Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology" . There's a section on the "Neurobiological effects of chronic benzodiazepines". Well worth checking out.

 

https://sci-hub.tw/https://www.researchgate.net/publication/341688809_Understanding_the_effects_of_chronic_benzodiazepine_use_in_depression_a_focus_on_neuropharmacology

 

Thanks Lapis

It’s a good article

 

 

I agree that antidepressants + benzos complicate the picture a lot

 

As the article states, the rigorous combination testing is horribly lacking (yet they are liberally and routinely prescribed in this manner)

 

The benzo neurogenesis angle is something that I had written about last year, and I believe what they are getting at, because adult neurogenesis is highly dependent on a properly functioning GABAergic system.  There’s tons of good research in this area.

 

As the article states, the acute vs. chronic effects of benzos are, in general, polar opposites, across a variety of systems.(See figure 1).

 

If we add voltage gated CCs, NOS, and immune system effects to figure 1,  that’s a good model.  It’s a very tangled web.

 

-cs123

 

I'm glad you had the chance to look at this study, cs123. Lots of good info in this one. I just had someone print it out for me so that I can take another look.

 

When they refer to "acute" and "chronic" in Figure 1, I wonder what the time frames are. Does "chronic" mean more than 4 to 8 weeks? In the very beginning of the paper, they mention the fact that "there are no efficacy trials published beyond 8 weeks", which is astounding, since SO many prescriptions carry on and on and on.

 

 

 

 

Here's the study I mentioned: "Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology" . There's a section on the "Neurobiological effects of chronic benzodiazepines". Well worth checking out.

 

https://sci-hub.tw/https://www.researchgate.net/publication/341688809_Understanding_the_effects_of_chronic_benzodiazepine_use_in_depression_a_focus_on_neuropharmacology

 

Thanks Lapis

It’s a good article

 

 

I agree that antidepressants + benzos complicate the picture a lot

 

As the article states, the rigorous combination testing is horribly lacking (yet they are liberally and routinely prescribed in this manner)

 

The benzo neurogenesis angle is something that I had written about last year, and I believe what they are getting at, because adult neurogenesis is highly dependent on a properly functioning GABAergic system.  There’s tons of good research in this area.

 

As the article states, the acute vs. chronic effects of benzos are, in general, polar opposites, across a variety of systems.(See figure 1).

 

If we add voltage gated CCs, NOS, and immune system effects to figure 1,  that’s a good model.  It’s a very tangled web.

 

-cs123

 

I'm glad you had the chance to look at this study, cs123. Lots of good info in this one. I just had someone print it out for me so that I can take another look.

 

When they refer to "acute" and "chronic" in Figure 1, I wonder what the time frames are. Does "chronic" mean more than 4 to 8 weeks? In the very beginning of the paper, they mention the fact that "there are no efficacy trials published beyond 8 weeks", which is astounding, since SO many prescriptions carry on and on and on.

 

Hi Lapis

 

You bring up a great point.  I would assume for the benzo, long term would be anything over 4-8 weeks per the standard big pharma literature

 

From a research perspective and a scientific perspective i think neuro-adaptations in “standard populations” start to occur in about 4 weeks and progressively get more entrenched once dependency develops and then tolerance. (They note tolerance in the figure 1)

 

It would be really interesting to do a statistically rigorous clinical trial for these chronic effects, but anything over 4-8 week benzo testing on humans isn’t ethical so patient data is the best we have.  I think there would be a very wide dispersion about the mean in real life populations, with some getting hit with “long term effects” as soon as 2 weeks(weaker stress resiliency), and others out 4-6 months.(strong stress resiliency) or never.

 

Thanks again for posting this article.  One thing I’ve noticed in the research , almost universally cortisol is lowered (in the absence of overt tolerance), and HPA cortisol response no longer responds to stress in an appropriate manner(ie, output should increase with stress, but does so only  in a “blunted” fashion due to benzo effects on CRH response).  Without proper cortisol response stress response deteriorates. This is one reason why stress resiliency decreases with benzo use.  This is paradoxical to why many go on benzos in the first place. 

 

 

-cs123

Hi cs123,

Yes, I've thought often about the impossibility of ever seeing the kind of data that we'd like to see. Those studies would be considered unethical to do on human beings, but it would be so enlightening to see the results. Obviously, each of our cases is so unique, and so many people end up being prescribed multiple types of medication at once. That muddies the water with regards to the data specifically about benzodiazepines. And data from rats and mice always leave me questioning whether such info can be extrapolated to human beings.

 

I'm glad you enjoyed the article, c123. I was quite pleased to see it as well, and I'd be even more pleased to think that prescribing physicians might actually read it! Here's hoping.....

 

 

 

 

Have you guys considered reaching out to the team at the University of Arizona who held the benzo withdrawal symposium?  They might be able to answer some these questions regarding possible studies on benzos. 

That article is unavailable, can someone maybe relate some info?

 

What does it say about ADs and benzos?  I was ok on benzos until an AD threw me into acute.

 

Thx

Yes, Barbara Ave., it looks like that particular link isn't working right now. I'll just post the abstract for now. It's on PubMed here:

 

https://pubmed.ncbi.nlm.nih.gov/32459725/

 

International Clinical Pyschopharmacology. 2020 Sep;35(5):243-253.

 

doi: 10.1097/YIC.0000000000000316.

 

Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology

Bryant Lim  1 , Beth A Sproule  2  3 , Zarin Zahra  1 , Nadiya Sunderji  4 , Sidney H Kennedy  1  5  6 , Sakina J Rizvi  1  5  6

 

Affiliations

Affiliations

 

    1

    Department of Psychiatry, St. Michael's Hospital.

    2

    Pharmacy Department, Centre for Addiction and Mental Health.

    3

    Leslie Dan Faculty of Pharmacy, University of Toronto.

    4

    Waypoint Centre for Mental Health Care, Penetanguishene, Ontario.

    5

    Department of Psychiatry.

    6

    Institute of Medical Sciences, University of Toronto, Canada.

 

    PMID: 32459725 DOI: 10.1097/YIC.0000000000000316

 

Abstract

 

Benzodiazepines are frequently prescribed on an ongoing basis to individuals with depression, mainly to alleviate anxiety or insomnia, despite current guideline recommendations that continuous use should not exceed 4 weeks. Currently, there are no efficacy trials published beyond 8 weeks. Several antidepressant trials demonstrate that the concomitant use of a benzodiazepine is associated with poorer depressive outcomes and functional status; however, it is unclear why this is the case. Patients with depression receiving a benzodiazepine may reflect a more ill or high anxiety group, although even within anxiety disorders, the use of a benzodiazepine is associated with poorer outcomes. The neuroadaptive consequences of long-term benzodiazepine use may be a factor underlying these findings. Chronic benzodiazepine use results in decreased gamma-aminobutyric acid and monoaminergic function, as well as interference with neurogenesis, which are all purported to play a role in antidepressant efficacy. This review will discuss the oppositional neuropharmacological interactions between chronic benzodiazepine use and antidepressant mechanism of action, which could result in reduced antidepressant efficacy and function in depression.

 

Maybe Sci Hub will be available at some point, but it's not the first time I've had issues trying to find something there. I don't have access to any online medical libraries, so I don't have another way to get this study. But I'm glad I was able to print it out before it became unavailable. Very frustrating!

Could it be that our Central Nervous Systems are inflamed and that is the reason for our various symptoms?  Also, the things that help me are things that naturally reduce inflammation like the keto diet, supplements like fish oil that I take, and exercise.  Also, I have recently been prescribed an anti-inflammatory medication for a problem I have with my knee.  I don't like taking any kind of medication so I have resisted taking them.  But I did take one today and I noticed that my symptoms decreased substantially.  I'm interested in hearing what you guys think.

Hi,

Yes, in part.  Immune factors and cytokines are very potent neuromodulators. And there are lots of different cytokines.

For example, NSAIDs in some studies have shown to have a statistically significant effect on neuropsychiatric disorders like depression (you can google the studies and find them easily) through this pathway

 

 

For PWS:

There’s a significant question as to cause and effect in the case of PWS, for example.  Is the immune system cytokine profile off kilter because of the protracted stress on the body, from PWS, and is that merely aggravating the PWS, or is the PWS onset itself caused by a disordered cytokine profile in those that have PWS?

 

Also there’s the greater question of the cross correlation of symptoms between extremely complex syndromes like CFS and fibromyalgia, for example, and the neurophysiology of PWS.

 

For example, benzos alleviate CFS symptoms in some patients, because the underlying neurophysiology of the CFS in these patents is biased toward hyperexcitability and this could be due in part to this irregular cytokine profile( this is as opposed to the other subset of CFS patients that are neurophysiologically biased in the opposite direction.  This might explain why benzos don’t help in all CFS patients)

 

The cytokines as neuromodulators is a very interesting area of study.

 

 

-cs123

 

All this is speculation. The cytokine hypothesis of psychiatric disease has been around for 30 years or more but it is still a hypothesis. Saying that inflammation causes this or that is not helpful.

 

 

Hi cs123,

Yes, I've thought often about the impossibility of ever seeing the kind of data that we'd like to see. Those studies would be considered unethical to do on human beings, but it would be so enlightening to see the results. Obviously, each of our cases is so unique, and so many people end up being prescribed multiple types of medication at once. That muddies the water with regards to the data specifically about benzodiazepines. And data from rats and mice always leave me questioning whether such info can be extrapolated to human beings.

 

I'm glad you enjoyed the article, c123. I was quite pleased to see it as well, and I'd be even more pleased to think that prescribing physicians might actually read it! Here's hoping.....

 

Hi Lapis

 

“And data from rats and mice always leave me questioning whether such info can be extrapolated to human beings. ”

 

I fully agree!

I’m not sure how long term studies with benzos can be performed on human beings given the big pharma disclosure on this class of drug.  I wouldn’t even want to subject the test subjects to such a risk  .