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I am a doc using the Road Back Protocol for the first time. The patient on 200 mg minocine twice daily (I know we started high) feels great the day of the drug, horrible the next day. On the weekends she feels horrible and really wants to take it more often. I have read through the physicians package and the studies on line and can't find the rationale for alternate day (or less frequent dosing). Can someone point me in the right direction to the answer to this question.
ps can't figure out how to delete a modicon sorry for the sad face.
Calgary Doc
Hi Calgary Doc,
Welcome to the RBF BB!
The best discussion I've found for the rationale in using pulsed dosing is in the book by Henry Scammell, “The New Arthritis Breakthrough,” which includes “The Road Back,” penned by Dr Brown, himself. Also, “The Infection Connection,” by Dr. Katherine M. Poehlmann is a great resource in this context.
In the physician's packet on the main RBF website, under the Education tab, however, there is a brief overview of the “hypersensitivity state,” which provides a synopsis of Brown's prime rationale for using low dose pulsing with the tetracyclines. I've cut and pasted the relevant piece below the link.
https://www.roadback.org/index.cfm?fuseaction=studies.display&display_id=184#Anchor-The-14210
The Hypersensitivity State (toc)
“The treatment approach in the microbial hyper-sensitivity state is determined to be altogether different from standard anti-microbial therapy. In rheumatoid disease, the hyperreactive state itself suppresses microbial antigen replication and accounts for the high degree of localization of mycoplasma foci of involvement. The primary objective of treatment is the suppression of antigen production and at the same time avoiding the sudden release of excess antigen and delayed drug sensitivity by over medication.
Effective treatment has evolved to be the converse of the treatment of standard infection. The dosage of medication is relatively low instead of high, it is generally interrupted instead of sustained, and the treatment is usually long-term.
In all microbial hypersensitivity states, the causative agent virtually goes underground as the tissue reactivity becomes manifest. Thus, in the highly reactive state, very little anti-microbial medication is needed to further control the disease. And if too much is given, the body begins to react against the medicine itself and defeats the purpose of the treatment. This is the main reason for the intermittent treatment. All bacterial hypersensitivity states require intermittent antigen suppressing treatment as exemplified by tuberculosis, rheumatic fever and brucellosis.”
From a patient/layman's perspective, my limited understanding of it is that the rising and falling serum levels of minocycline elicit a state of controlled herxing that is more tolerable to the patient in lower doses. In this context, herxing is a good sign, because it means die-off is occuring as the body is reacting to the release of pathogenic toxins being emitted. However, the goal of low dose pulsing is to keep the herxing tolerable to gradually “retrain” the immune system to function normally on its own and to bring the rheumatoid patient's hypersensitive state into one of relative quiescience.
On the other hand, constant serum levels of minocycline (after an initial herx period) are believed to be more immunosuppressive (as per the ACR's recommendations of mino for DMARD use). While some amount of pathogenic die-off probably still occurs on 100mg bid minocycline, it's the rising and falling serum levels that seem to evoke greater die-off, hence why some patients may feel worse on their pulsed “off” days. I actually felt worse within a few hours of taking my mino and much better on my day off. So, it seems to vary amongst patients (maybe due to pathogen type/load?) as to whether they feel better on their “on” or “off” days.
John McDonald is one of the better-versed patient advocates here who may be able to give you a much more informed, scientific perspective.
Peace, Maz
Calgary Doc – you will also find a private message waiting for you in the above right hand corner of this page with further information, which can be retrieved by logging in and clicking on “1 new message.”
Thank you for your interest.
Maz
Hi Doc,
There is an other protocol that gives a very good explanation. http://www.marshallprotocol.com It is terribly difficult to follow but the information in it is priceless. LynneThanks Lynne, I have read the Marshall Protocol before but I think it's time to give it another look. Ellie
Doc,
My background is physics, not medicine so I am not qualified to speak to this, but if you are still with me after that caveat I will relate my thoughts on QOD dosing. I generally prefer to speak about personal experience vs. theory with which I am only passingly acquainted but here goes.
Firstly the QOD dosing is predicated on the theory that the etiology is microbial and that the microbes are slow dividers such as the Mycoplasmas or Mycobacterias. So in that light it is thought that having a strongly varying serum level is not going to give the microbes any advantage. Since this is a long term therapy it is a big advantage to the patient to deal with much less antibiotic. The antibiotics don't have much in the way of side effects but they do cause dizziness and GI tract discomfort and that is considerably reduced if the patient doses QOD or MWF. There is also the Jarisch-Herxheimer effect in which the patient temporarily feels much worse due to bacterial die off. Marshall thinks that is due to macrophage apoptosis when the immune system becomes aware that the macrophages are infected. The herx can be quite difficult as with your patient but it can be moderated by decreasing or increasing the dose and frequency. That bit I can definitely speak to from personal experience. Oddly enough sometimes dosing BID can make the herx much easier to bear and dosing QOD can make it more difficult.
The herx experience can occur on either the dose day or the off day but I see it most commonly reported on the off day just as your patient is experiencing it. I have experienced it both ways but for me too it was and is more common and stronger on the off day. I follow Marshall respecting this, in that doc lets me adjust my antibiotics quantity to make the herx tolerable. I started with a small dose and worked up to a larger dose, but in my case always QOD.
Many physicians believe that Minocycline's benefit is primarily immuno-suppressive. Those physicians choose to dose BID to keep the serum levels high and constant. Many patients on this site dose 100mg BID and they improve nicely over the long haul, just as the pulse dosers do. We have had debates amongst us patients about which regimen is better but the fact is that both BID and QOD work. But some patients have a difficult time with either one or the other. I happen to think that the QOD or MWF dosing is more effective in the long run and may produce results more quickly but there is no doubt in my mind from watching this site over several years that BID dosing also brings considerable relief.
These bacterio-static antibiotics, especially Minocycline are known to be both immuno-suppresive and anti-bacterial. Marshall argues that you can emphasize the immuno-suppresive properties of Minocycline, by frequent dosing (BID) and can emphasize the antibacterial properties by pulse dosing. Many of the Marshall cohort report that their herx responses are greatest when the Minocycline serum levels are at the 48 hour minimum. The story that may go with that is that the initial high dose of Minocycline suppresses both the immune system and the microbe, but at some serum level or rather at some ebbing tissue concentration, the immune system may recover before the microbe and with that advantage can destroy the microbe, thereby eliciting a herxheimer response. I don't know if that is true, but it describes my own experience with respect to dosing and eliciting herxheimers so I find the explanation attractive.
To me the key to this therapy is the herx experience. I can't think of any better explanation for a reliable, repeatable Jarisch Herxheimer response other than bacterial destruction. My personal herxheimer experience, together with my indisputable recovery from RA makes me strongly favor the microbial etiology. The real challenge to me was Marshall's assertion that a herx is necessary, even desirable for healing. That is controversial on this website and you will find patients here who report considerable recovery, even remission without a definable herxheimer experience. However it is nevertheless an intriguing claim. Mycobacteria and Mycoplasmas and Chlamydias are well known to parasitize the macrophages that would ordinarily be tasked with eliminating them. It is plausible that the Th1 immune cells once awakened to the infection might opt to destroy infected macrophages just as they destroy cells infected with virus. And it is plausible that macrophage apoptosis might well dump all sorts of inflammatory cytokines in situ. It is easy to imagine inflammation getting worse before it gets better. So Marshall's claim seems reasonable in that light, that if you can elicit herxing then you should do so.
This is your field, not my own. So you will be in a much better position than I to understand and validate or dispute these things. This is a small part of the story that I have assembled to explain my own remarkable recovery on this protocol. I am uncomfortable speaking about the theory but I can assert with confidence that when I started AP my disease immediately went from stable to unstable, good days and bad days, good weeks and bad weeks, for about 8 glacial months. At that point I became surprised that undetected to me I had actually improved quite a lot. After 8 months I caught myself carrying about 6 or 8 heavily laden plastic bags of groceries from car to house. I could not have done that when I started AP. In 3 more months I was beginning to speak about possible remission. Now after a few years using my own numbers I say that I am 97% or 98% cured of Rheumatoid Arthritis. RA just isn't a part of my life anymore. I am on the Marshall Protocol and I can still elicit a trace of arthralgia late in the 10-day antibiotic cycle but the inflammation occurs in only 2 or 3 days out of 10 now, and only amounts to about 1/4 to 1/2 of 1 out of a scale of 10 or so. I can't be troubled to take an aspirin for it. The AP/MP protocol has been really effective.
I hope this has been helpful. Thank you for working with your patient with antibiotics.
John McDonald
John thanks for that detailed response and for the observation that there is flexibility in the dosing schedule. Also for sharing the commonalities between Road Back and Marshall. It's a bit scary to be prescribing antibiotics in a medical world that frowns upon such endeavors. My patient is already appreciating the feedback.
Ellie Stein
Calgary Doc,
I've been reading this thread with much interest and must tell you, thank you for being one of the few docs willing to go against the tide to do what is best for the patient. I wish there were more like you in the world.
— whaleharbor
Minocycline 100mg every other day with food...lots of food: Zydus brand. Celecoxib 200mg twice per day: Greenstone brand.
Hi
If you wish the phone number of the doctor up at Harvards Beth Israel Deaconess Hospital in Boston would be gladly supplied –he is a very strong advocate of daily dosing and would be very willing to discuss it with you –he was principal investigator for the MIRA studies as well as conducting studies on scleroderma and the use of minocycline —
Richie
Dear Calgary Doc – you will find the rationale for pulse dosing in the material Maz pointed you to. You will find more at the site http://www.rheumatic.org . This is NOT a regime where more is necessarily better – often the reverse and protocols often have to be tweaked for individual patients. Yours may be having a herx response (and that is a good thing) on the off mino days. I had great success on MWF dosing over 5 years and never had a yeast problem (even before pro-biotics were started).
There is alot of good info in this lecture by Harold W Clark, a long-term colleague of Dr Brown's (a microbiologist I believe). It includes a pulse dosing rationale. Link is pasted below. Great that you are taking so much interest. Lynnie
Be well! Lynnie
Palindromic RA 30 yrs (Chronic Lyme?)
Mino 2003-2008 100mg MWF - can no longer tolerate any tetracyclines
rotating abx protocol now. From Sep 2018 MWF - a.m. Augmentin Duo 440mg + 150mg Biaxsig (roxithromycin). p.m. Cefaclor (375mg) + Klacid 125mg + LDN 3mg + Annual Clindy IV's
Diet: no gluten, dairy, sulphites, low salicylates
Supps: 600mg N-AC BID, 1000mg Vit C, P5P 40mg, zinc picolinate 60mg, Lithium orotate 20mg, Magnesium Oil, Bio-identical hormones (DHEA + Prog + Estrog)
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