Severely Depressed from Die-Off/Herx? Probiotics? Virus? Lyme? Co Infection? What's Happening?

[Hip]

The antidepressant remedies I find very useful when depression hits, as it seems to do on random weeks with me, are:

Inositol powder 1 to 3 heaped teaspoons.
Saffron 60 mg of stamens (has to be Spanish or Iranian saffron). Some small-scale studies have shown saffron to be as potent an Prozac, but without the side effects of SSRIs.
NADH 5 to 10 mg.
Raw chocolate 2 to 4 heaped teaspoons — a strong energy booster that has anti-depressant effects. Raw chocolate is like regular chocolate on steroids!
Pregnenolone 50 mg — pregnenolone boosts hormone levels in general, which I find helps pick up your mood.

Wolfberries (Goji berry) — eating a handful of dried nice wolfberries gives a nice mood boosting, antidepressant effect, but higher doses can cause diarrhea.
Ravensara essential oil drops diluted in 30 ml carrier oil (like baby oil) and rubbed on the skin, where it gets absorbed. This herb creates a happier mood, and is also antiviral.
Imipramine 25 mg — imipramine is an excellent TCA antidepressant like amitriptyline, but has lower side effects. Vitamin B6 may improve effectiveness of TCA antidepressants. It is best to take vitamin B2 with TCA antidepressants, as TCAs can deplete vitamin B2.
Amisulpride 12.5 to 25 mg daily works very well to combat depression, though it reduces libido.

I went through one or two years when depression was a constant battle, and I would take several of the above simultaneously. Nowadays my depression only comes back now and then, and to a lesser degree, but I still use the above remedies when it does.

 

[Lotus97]

It is best to take vitamin B2 with TCA antidepressants, as TCAs can deplete vitamin B2.

That's good to know about tricylic antidepressants. I've been on amitriptyline for years (as a sleep aid). I was actually planning on upping my dose of B2 anyways. I'm switching to the coenzymated form after someone told me you can only absorb around 30 mg of the non-active B2 at a time.

 

[Lotus97]

I've been taking probiotics for a couple of days and I'm getting depressed again. Although I am going to stop the probiotics, there is another possibility. I didn't share my original hypothesis because it seemed unlikely. When I first got depressed 2 months ago it happened around 8 days after I started a new bottle of Prozac. Although the Prozac was by the same generic company as before I wondered if it was a bad batch. When I had gone off Prozac in the past it took about 8 days before I got depressed because Prozac has such a long half life. When I switched to taking 20 mg capsules my mood improved. Now I've been off the 20 mg Prozac for about 8 days (I switched to Paxil) and I'm getting depressed. I will see if stopping the probiotics for a few weeks makes a difference, but I don't want to rule out the other possibility.

 

[triffid113]

Did I read that right, that the person you mention, Velha, took 5 grams of L-carnitine fumarate? I have never gone above around 1.5 grams per day when I take L-carnitine. Sounds like a rocket fuel approach to treating ME/CFS!

Yes, you read me right. I may be wrong, but it was at least 3.5 g / day. I am guessing she is supplying all the carnitine she needs via supplement rather than via the methyl cycle. It makes me think maybe she needed TMG and did not take it. Or maybe she was hyperthyroid and using up carnitine faster than normal. Or??? She specualted that she has a - well I forget - I think she might have said some sort of fat metabolism issue. Once she foud what worked she stuck with it. It worked for her sister too.

 

[Lotus97]

It seems with me there's some kind of herx going on which is causing the depression rather than the cytokine flare that some people suggested. For anyone following this thread who does suspect a cytokine induced depression for themselves I found what seems to be a pretty good explanation as to why it happens
The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans
by
Wichers M, Maes M.
Department of Psychiatry and Neuropsychology,
Maastricht University, 6200 MD Maastricht, The Netherlands.
Int J Neuropsychopharmacol 2002 Dec;5(4):375-88

ABSTRACT

Administration of the cytokines interferon-alpha and interleukin-2 is used for the treatment of various disorders, such as hepatitis C and various forms of cancer. The most serious side-effects are symptoms associated with depression, including fatigue, increased sleepiness, irritability, loss of appetite as well as cognitive changes. However, great differences exist in the prevalence of the development of depressive symptoms across studies. Differences in doses and duration of therapy may be sources of variation as well as individual differences of patients, such as a history of psychiatric illness. In addition, sensitization effects may contribute to differential responses of patients to the administration of cytokines. In animals administration of pro-inflammatory cytokines induces a pattern of behavioural alterations called 'sickness behaviour' which resembles the vegetative symptoms of depression in humans. Changes in serotonin (5-HT) receptors and in levels of 5-HT and its precursor tryptophan in depressed people support a role for 5-HT in the development of depression. In addition, evidence exists for a dysregulation of the noradrenergic system and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis in depression. Some mechanisms exist which make it possible for cytokines to cross the blood-brain barrier. Pro-inflammatory cytokines such as IL-1beta, IFN-alpha, IFN-gamma and TNF-alpha affect the 5-HT metabolism directly and/or indirectly by stimulating the enzyme indoleamine 2,3-dioxygenase which leads to a peripheral depletion of tryptophan. IL-1, IL-2 and TNF-alpha influence noradrenergic activity and IL-1, IL-6 and TNF-alpha are found to be potent stimulators of the HPA axis. Altogether, administration of cytokines may induce alterations in the brain resembling those found in depressed patients, which leads to the hypothesis that cytokines induce depression by their influence on the 5-HT, noradrenergic and HPA system.​

 

[Lotus97]

Someone just started a thread saying curcumin caused a herx with them. One person suggested in that thread suggested that it was because curcumin was a Th2 stimulant and many people here are Th2 dominant. I was also reading that probiotics can initiate a Th2 immune response so I'm considering that a possibility to why I had the reaction I did. I also found out that some of the cytokines mentioned in that article about cytokine-induced depression are associated with Th2 responses (also others are associated with Th1 responses). I noticed this mentioned monocytes and my monocytes were high last time I was tested.

 

[Lotus97]

I recently found out that ginger and turmeric both have antibacterial, antifungal, antimicrobial, and antiviral properties. I've been taking Zyflamend PM twice a day (4 capsules total) which has very potent full spectrum extracts of ginger and turmeric. I guess I'll stop those for awhile too.

 

[Jarod]

Lotus97 I started dumping heavy metals from methylation startup which made me terribly depressed. This was measured with a pee test.

I may have been going too fast, but dumping metals (especially during the initial startup) can make one terribly depressed.

 

[Lotus97]

I wasn't going to post any more in this thread unless I thought there was information I thought would be useful to others. It seems with me, the depression was (and is) due to inflammatory cytokines. Part of this was from the probiotics causing a herx which can cause inflammatory cytokines. I confirmed this after taking various antibacterial/fungal/microbial supplements and experiencing the same depression. There seems to be more, however. I was taking immune supplements that stimulate Th1 and Lyme can also cause an overactive Th1 immune response. I posted about it in this thread:
http://forums.phoenixrising.me/inde...in-late-stage-lyme-and-buhner-protocol.22068/
Part of the inflammatory Th1 response seems to be due to microglia. The first article talks about microglia in regards to infectious diseases in general, but does have a section specifically about Lyme. The second and third are about microglia and Lyme specifically. The last article (which the diagram is from) talks about inflammation in regards to glutamate, microglia, and depression. Except for the third article, there is a lot more information than what I'm posting here so anyone who wants to learn more about this subject I'd recommend following the links to the full articles. Only the second and third article are specifically about Lyme. The first and fourth article are broader in their scope (although the first one does have a section devoted specifically to Lyme as I mentioned earlier).
===========================
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847353/
Microglia in Infectious Diseases of the Central Nervous System
Abstract

Microglia are the resident macrophage population in the central nervous system (CNS) parenchyma and, as such, are poised to provide a first line of defense against invading pathogens. Microglia are endowed with a vast repertoire of pattern recognition receptors that include such family members as Toll-like receptors and phagocytic receptors, which collectively function to sense and eliminate microbes invading the CNS parenchyma. In addition, microglial activation elicits a broad range of pro-inflammatory cytokines and chemokines that are involved in the recruitment and subsequent activation of peripheral immune cells infiltrating the infected CNS. Studies from several laboratories have demonstrated the ability of microglia to sense and respond to a wide variety of pathogens capable of colonizing the CNS including bacterial, viral, and fungal species. This review will highlight the role of microglia in microbial recognition and the resultant antipathogen response that ensues in an attempt to clear these infections. Implications as to whether microglial activation is uniformly beneficial to the CNS or in some circumstances may exacerbate pathology will also be discussed.
Keywords: microglia, bacterial meningitis, brain abscess, Lyme neuroborreliosis, Toxoplasmaencephalitis, cerebral malaria, fungal infections, review
Microglial recognition of Borrelia burgdorferi and Lyme neuroborreliosis

The spirochete B. burgdorferi (sensu lato) is the etiologic agent of Lyme disease, the most frequently occurring vector-borne infection in the USA (Hengge et al. 2003; Rupprecht et al. 2008). B. burgdorferitransmission occurs through Ixodes ticks and is also endemic in Europe and parts of Asia. Lyme disease initially propagates in the skin before it disseminates through the blood stream to other organ systems. In addition, B. burgdorferi displays tissue tropism for the nervous system, where neurologic involvement occurs in up to 20% of patients who present with cranial neuritis, meningoradiculitis, or encephalitis (Pfister et al. 1994; Rupprecht et al. 2008). Colonization of the CNS with B. burgdorferifrom the blood is associated with inflammation of the meninges, nerve roots, brain, and spinal cord resulting in the clinical manifestations of neuroborreliosis (Pfister and Rupprecht 2006; Rupprecht et al. 2008). Furthermore, marked levels of pro-inflammatory molecules such as IL-6 and TNF-α are associated with Lyme disease, as well as the induction of an important inflammatory enzyme, cyclooxygenase-2 (COX-2; Ramesh et al. 2008; Rasley et al. 2002). However, the inflammatory mechanisms that are involved in the CNS immune responses to B. burgdorferi are not currently well understood based on the limited availability of an adequate animal model. To date, the only animal model where evidence of Lyme neuroborreliosis has been demonstrated is in rhesus macaques (Pachner et al. 2001).
===========================
http://www.ncbi.nlm.nih.gov/pubmed/12225885
Borrelia burgdorferi induces inflammatory mediator production by murine microglia.

Abstract

Lyme disease has been associated with damaging inflammation within the central nervous system. In the present study, we demonstrate that Borrelia burgdorferi is a significant stimulus for the production of IL-6, TNF-alpha, and PGE(2) by microglia. This effect is associated with induction of NF-kappaB, and increased expression of Toll-like receptor 2 and CD14, receptors known to underlie spirochete activation of other immune cell types. These studies identify microglia as a previously unappreciated source of inflammatory mediator production following challenge with B. burgdorferi. Such production may play an important role during the development of Lyme neuroborreliosis.
===========================
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000659
Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis in SH-SY5Y Neuronal Cells
Abstract

Inflammation has long been implicated as a contributor to pathogenesis in many CNS illnesses, including Lyme neuroborreliosis. Borrelia burgdorferi is the spirochete that causes Lyme disease and it is known to potently induce the production of inflammatory mediators in a variety of cells. In experiments where B. burgdorferi was co-cultured in vitro with primary microglia, we observed robust expression and release of IL-6 and IL-8, CCL2 (MCP-1), CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES), but we detected no induction of microglial apoptosis. In contrast, SH-SY5Y (SY) neuroblastoma cells co-cultured with B. burgdorferiexpressed negligible amounts of inflammatory mediators and also remained resistant to apoptosis. When SY cells were co-cultured with microglia and B. burgdorferi, significant neuronal apoptosis consistently occurred. Confocal microscopy imaging of these cell cultures stained for apoptosis and with cell type-specific markers confirmed that it was predominantly the SY cells that were dying. Microarray analysis demonstrated an intense microglia-mediated inflammatory response to B. burgdorferi including up-regulation in gene transcripts for TLR-2 and NFκβ. Surprisingly, a pathway that exhibited profound changes in regard to inflammatory signaling was triggering receptor expressed on myeloid cells-1 (TREM1). Significant transcript alterations in essential p53 pathway genes also occurred in SY cells cultured in the presence of microglia and B. burgdorferi, which indicated a shift from cell survival to preparation for apoptosis when compared to SY cells cultured in the presence of B. burgdorferi alone. Taken together, these findings indicate that B. burgdorferi is not directly toxic to SY cells; rather, these cells become distressed and die in the inflammatory surroundings generated by microglia through a bystander effect. If, as we hypothesized, neuronal apoptosis is the key pathogenic event in Lyme neuroborreliosis, then targeting microglial responses may be a significant therapeutic approach for the treatment of this form of Lyme disease.
===========================
http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1590
Inflammation, Glutamate, and Glia in Depression: A Literature Review
Abstract
Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-α treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.
Introduction
Depression is a common and debilitating disorder for which current treatments are inadequate. The pathogenesis of depression is not well understood. The annual prevalence of depression is 7% and the lifetime prevalence is 16%.1,2 In addition to significant disability,3depression is associated with excess mortality,4,5 particularly from cardiovascular disease.6 Current antidepressants, which target monoamines, only produce remission in 30% of patients. Part of the problem lies in the fact that the pathophysiology of depression has not been elucidated, and treatments are based on empirical data, not mechanisms of action. It remains unclear how these drugs actually work, since their ability to increase synaptic concentrations of monoamines is immediate, while their clinical effects take 2–4 weeks to become apparent.7 The aim of this article is to provide an overview of studies implicating inflammation in depression, and propose a model of how excess inflammation may interact with glutamate and glia to cause depression.

 

[adreno]

I'm on Candex which is an antifungal, and the die-off seems to cause severe depression for me as well. Perhaps this is common in herxing.

 

[Lotus97]

Lotus97 I started dumping heavy metals from methylation startup which made me terribly depressed. This was measured with a pee test.

I may have been going too fast, but dumping metals (especially during the initial startup) can make one terribly depressed.

It seems like the depression from die-off/herx is caused by inflammation, but I wonder if the same thing is going on with the metal dumping. Besides Jarod, I've heard from one or two other people with metal toxicity who say they've experienced depression from too much methylation.
http://www.ncbi.nlm.nih.gov/pubmed/9707512
Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms.
Abstract
Hepatocytes, as well as nonparenchymal cells, secrete proinflammatory cytokines and chemokines that are involved in the pathology of many liver diseases. In particular, tumor necrosis factor-alpha (TNFalpha), as well as members of the CXC family of chemokines, including interleukin (IL)-8 in humans and macrophage inflammatory protein (MIP)-2 in rodents, have been implicated in both damage and repair processes associated with various hepatotoxins. In the liver, cytokine secretion is usually associated with nonparenchymal cells, particularly Kupffer cells. In the present studies, cytokine gene expression and secretion were investigated in hepatocytes treated with cadmium chloride (CdCl2) or vanadium pentoxide (V2O5). Using human Hep G2 cells and freshly isolated rodent hepatocytes, it was demonstrated that metals increase gene expression and secretion of CXC chemokines and TNFalpha. IL-8 and MIP-2 secretion induced either by the metals or H2O2 were inhibited by antioxidants such as tetramethyl-thiourea and N-acetyl-cysteine. In vitro neutralization experiments with TNFalpha and in vivo studies with TNFalpha receptor knockout mice indicated that the metals directly stimulate CXC chemokine secretion without the need for TNFalpha. Taken together these studies indicate that, in addition to other inflammatory mediators and acute phase proteins, cytokines and chemokines are produced by hepatocytes, which may participate in hepatotoxic responses. The events responsible for their expression involve cellular redox changes.

 

[Lotus97]

I found this from Wikipedia. Among the ones mentioned, tumor necrosis factor (TNF) and interleukin-6 (IL-6) are both linked to depression in the articles I posted earlier.
http://en.wikipedia.org/wiki/Jarisch-Herxheimer_reaction

The Herxheimer reaction has shown an increase in inflammatory cytokines during the period of exacerbation, including tumor necrosis factor alpha, interleukin-6 and interleukin-8

Also from an article on Herxheimer reaction. IL-1 and interferons (such as IFN-alpha and IFN-gamma) are also linked to depression.
http://www.jemsekspecialty.com/lyme_detail.php?sid=10

It is widely recognized that antibiotic therapy may promote endotoxin release by virtue of its microbicidal effect which leads to the disintegration of the bacterial organism and exposure, or presentation, of endotoxin. On recognition of the endotoxin, polypeptides such as IL-1, interferons, or tumor necrosis factor (TNF), otherwise referred to as endogenous pyrogen (EP) or pyrogenic cytokines, are released by the monocyte/macrophage system (115). It should be pointed out that only minute quantities of EP are needed in order to generate fever and other systemic symptoms.

Just as a side note I've had my monocytes tested twice. Both times they were high, but during the period where I had been making a recovery they were lower (from 9.4 to 7.7). Also, my sedimentation rate was high both times, but it was also lower during the period where I was making a recovery.

 

[merylg]

And another probiotic supplement I'm taking is very similar to homemade yogurt mentioned. It's freeze dried fermented cabbage. I'm taking different brands because I wanted to populate my gut with as many different strains of probiotics as possible.

I found I could not tolerate the amines in Sauerkraut.

 

[lch1]

About a month ago I started to get really depressed. I've been having a lot of health problems for the past 5 months, but my mood had remained relatively good until last month. I've been on a lot of antidepressants over the past 15 years so I know when they're working and when they're not, but I still considered that possibility initially. My AD was working so well in fact that sometimes I actually felt stoned (and no I didn't smoke anything). Maybe there was some synergy with my supplements, but it was mostly the anti depressant. Aside from increasing serotonin, Prozac actually has dopaminergic properties.

I've been considering other options and the one that seems most likely is this. I started to get depressed right around the same time I began taking probiotics. I had been taking probiotics before, but I stopped for the month. I've also been taking prebiotics which some people say can make probiotics significantly more effective. I've heard that probiotics can cause a herx/die-off/Herxheimer effect in some people. And then some people experience depression from herx caused by antibiotics, antifungals, probiotics, antivirals, etc. I'm 98% sure I have Lyme disease so I was if when I started taking the probiotics if they triggered some kind of reaction in my body which is now fighting something. I'm also taking a few supplements for the immune system, but I'm not sure how they work. I've noticed when I've taken Pau D'Arco tea I've sometimes been depressed or moody, but it passed relatively quickly that I can't be sure if it was caused by that or not. I'd like to know
1. Is any of this possible?
2. Why is it happening?
3. What can I do about it?

Yes, I believe staring probiotics does cause a great deal of discomfort, including depression, flu-like symptoms, joint pain and even fever and upper respiratory stress. It is happening to me right now and I'm sure it's the probiotics. I'll continue because it should stop within a couple of weeks. If it doesn't subside, I'll just stop or cut down the dose to a quarter.

 

[digital dog]

Could it be that your antidepressants have stopped working? If you have been on different antidepressants for 15 years you may find that you are encountering this.
Sorry, not what you want to hear but these drugs do not work indefinitely.
Probiotics can definitely cause depression though.

 

[heapsreal]

Alot of serotonin is made in the gut, so I wonder if changing gut environment can change serotonin metabolism in some way.

I recently had some candida and mood was getting low. Treating this with antifungals and probiotics has improved my mood not just candida symptoms , so its made me wonder about serotonin/gut relationship???

 

[Violeta]

Reishi might be a better choice for working on the gut when probiotics cause side effects, because it also is antiviral and an antibacteriostat

http://www.ncbi.nlm.nih.gov/pubmed/24940906

Besides being antiviral and antifungal, it comes with it's own antioxidants to deal with oxidative stress.

http://www.ncbi.nlm.nih.gov/pubmed/20214017

 

[Gondwanaland]

I am glad this thread got bumped up. Yesterday my husband took S. boulardii at bed time and today he is feeling "the whole burden of the world on his shoulders".

Reishi might be a better choice for working on the gut when probiotics cause side effects

He has FODMAPs problems and can't tolerate mushrooms... I think I will follow one of Hip's suggestions above. Chocolate!

 

[lch1]

After years of back and forth with unfounded depression (I am NOT a depressed person--I am excited and interested in the world!), I finally found the answer. On and off of zoloft over the years, I decided I could not STAND the see-saw effects of those medications. I asked for Wellbutrin and secretly started taking a QUARTER OF A 75 MG TAB each day. That amount is laughable to psychiatrists. However, it works! It has worked for well over a year now. What that does is give me just enough boost of serotonin without overwhelming me. Also, I fortunately have found a doctor who was willing to go along with this hairbrained idea, and he admits we are on to something! Taking more and more, and full doses of antidepressants puts you in a place where you have way too much. So, I hope some people are helped by this post. Just a wee bit each day (and I do miss one or two days a week, not more) will do the trick.

 

[outdamnspot]

I was wondering if anyone else has experienced depression with gut treatments? Is this just part of the initial immune activation?

My depression is severe anyway (endogenous, plus having CFS is depressing). I started Symbioflor (e coli probiotic) last night and feel horrible today; just empty and constantly on the verge of tears.