Tuesday, October 29, 2019

Disulfirm/Antabuse

Its true: Antabuse/disulfiram is the most exciting new therapy for Lyme since daptomycin.

We are getting a lot more experience with disulfiram/Antabuse.  In some cases, it seems to be very effective.  I don’t think it is clear which microbes it is active against. It is an old drug repurposed as an antibiotic.  Its antimicrobial spectrum may remain unknown for the foreseeable future (there is no money researching it).  One thing worse than dreaded MRSA is VRSA – vancomycin resistant Staph aureus.  In vitro it was shown that the addition of disulfiram to vancomycin conferred the ability to kill this dreaded superbug. This should be catching some eyes, even outside the Lyme world.

Disulfiram clearly has potent antibiotic effects. It also has side effects. Twenty five percent of users have some rise in liver function tests –markers of liver inflammation. The rise is usually modest, and therapy can continue if AST/ALT numbers don’t exceed 2-3 twice the normal limit, with close monitoring. Three times makes me nervous. My comfort zone limits closer to 2.  Waiting for numbers to normalize and restarting with a lower dose may work. Severe liver disease may occur 1-2% of the time, not a trivial number.

ONLY YOUR DOCTOR CAN MAKE CLINICAL DECISIONS REGARDING ANTABUSE AND LIVER TEST.  THIS IS WRITTEN FOR GENERAL INFORMATIONAL PURPOSES ONLY; FULMINANT LIVER DISEASE CAN BE FATAL.

You should never treat yourself. The man who has himself as his doctor has a fool for a patient.

Side effects may include, dizziness, brain fog, fatigue, GI intolerance and others – in my patients. Many patients have had to discontinue because of side effects. Monotherapy may be fine. It runs counter to my experience, so I tend to prescribe it with doxycycline.

A word for the wise. We don't really know how safe the drug is.  Sometimes problems only become known when an occasional drug becomes one in common use. We have seen it over and over, for example, fenfluramine off fen-fen fame caused unexpected heart and lung disease and Vioxx the great new anti-inflammatory caused heart disease. Drug companies who have studied drugs extensively and had FDA approval call this "post-marketing" side effects.

Yes, Antabuse is an old drug used by hundreds of recovering alcoholics. When this old drug, largely disregarded from decades, it is suddenly used by thousands of lyme sufferers it many ways acquires characteristics of a new drug. In this case one that has not been tested. Quality control of generics is increasingly becoming an issue, e.g. Zantac.

I am prescribing the drug, just not throwing caution to the wind.

There is the issue of dose.  For alcoholics the loading dose is 500 mg and maintenance dose is 125-250 mg. This suggests that lower doses have efficacy.

There is some confusion about Lyme Herxheimer reactions.  From experience, Lyme, Babesia and Bartonella have separate and distinct Herxheimer responses.  Herxheimer reactions occur when mass killing of chronic, entrenched infection leads to an over-reaching immune response, a cytokine storm. The average, non-Lyme doctor, is unaware of the phenomenon treating mostly acute infections. These same doctors no doubt encounter a fair number of Herxheimer reactions which are misdiagnosed, e.g. drug allergy. Some patients have an “allergy” to every antibiotic. No, they don’t. Other patients say, “every time I take an antibiotic it hits me hard.”

Babesia and Bartonella Herxheimer reactions are very vexing, chronic and sometimes difficult to manage. They are qualitatively different from Lyme Herx reactions.

Lyme “Herxes” tend to be easier and follow a specific pattern.  An antibiotic is introduced, with days severe symptoms ensue, like fatigue (inability to get out of bed fatigue) low grade fevers, brain fog, achiness etc. After a period of days, weeks, usually no more than 3 weeks, symptoms begin to improve and go away and the patient improves. The Herxheimer reaction (Lyme only) should not return in cycles. Such cycles, apparent recurring Herxes, may be the result of normal ups and downs of the disease or due to killing something else other than Lyme. If we add one or more drugs, which gain access to a previously off-limits group of bacteria (round forms, biofilms etc.) a Herx may return, maybe even a more difficult Herx.

Dr. Zhang has dichotomized Lyme bacteria for us: active forms (free spirochetes) and stationary/persister forms (round bodies, biofilms).

After a reasonable amount of treatment with antibiotics targeting both populations, e.g. doxycycline, rifampin and Flagyl we would like to think there are few Lyme bacteria left. We are incorrect.

Add in disulfiram and an intense Herxheimer reaction may ensue (in some cases, not all).  Patient tolerance to  varying doses of the drug is all over the map.  Some handle 500 mg out of the gate, others struggle with 125 every other day.

It makes sense to start with a low dose and gradually increase over time.  I am more aggressive apparently than many others.  Most patients can increase from 250 mg daily ramped to 500 mg over a week or two. For sensitive patients much lower doses and more gradual ramping is required.

I have seen patients on the border of needing IV antibiotics  get better with Disulfiram.

It doesn’t always work. There is still no one drug that works for every patient.  And symptoms still relapse quickly with discontinuation after a few months.  Some patients are still going to need IV antibiotics, (Rocephin, daptomycin, doxycycline) if possible.

In my experience disulfiram doesn't appear to kill Babesia. My experience. Babesia is an opportunistic infection riding on Lyme’s coat tail.  Lyme has inherent immune suppressing properties. If Lyme is largely gone, Babesia symptoms may abate as well. In a normal host the body's immune system can eradicate Babesia, or reduce it to a mild parasite causing no symptoms. Just a thought.

So far, we only know that Antabuse kills Lyme spirochetes and Staphylococcus. Hopefully research will be funded so we can learn more about the drug. We really don't know what it does or doesn't kill.

Bottom line: Go for it! Monitor labs, watch for side effects (no alcohol including herbal tinctures): disulfiram –is  not an overnight miracle cure -- but it is quickly rising to the top of the list of  go-to Lyme drugs.  

2 comments:

Unknown said...

Dr. Jaller,

What are your thoughts on the use of disulfiram versus other persister drugs particularly Dapsone in patients who have failed conventional protocols?

Dapsone has certainly received a lot of hype over the years, but certainly has not turned out to be what some thought it would have. Perhaps the same will be true in the case of Disulfiram.

Lyme report: Montgomery County, MD said...

No. It is not the same.

And, there is no such thing as a conventional protocol. Optimal Lyme therapy is an evolving work in progress.

Dapsone failed to work in a test tube and Zhang at Hopkins took a good look at it.

Disulfiram was extremely effective in a test tube, Stanford.

Caveat: drugs that work poorly in test tube may work very well in vivo (living subject). The opposite is true as well.

FDA drugs can be repurposed if there is a sound clinical or scientific basis. In my experience, dapsone was a bust. Disulfiram has been clinically effective. Disulfiram is being studied scientifically, Fallon/Columbia. Results wont be known for a year or two. There may be design flaws, e.g. patients treated for only 8 weeks/dose too high/high drop out rate due to side effects, etc. Patients who are desperate and very ill understandably do not want to wait for publication of a peer reviewed publication. Its likely the results will be contested even if benefits are clear. Fallon has been through this already.

Dapsone did not work for my patients and I stopped using it. Disulfiram appears surprisingly effective for many patients. Many naysayers(mostly doctors) state clinical experience is no substitute for good clinical research. It is too early to use the drug. Detractors might even say it is irresponsible to use the therapy. (maybe in the best of all possible worlds this is true, however, that is not the world we live in). I have two things to say: Placebo effects are common but benefits do not persist and therefore clinical experience is very important and Lyme deniers should get Lyme disease, perhaps his/her perspective will change. (You don't get it until you get it).

Translational medicine is well accepted in cancer. Why is Lyme different?

In balancing risk v benefit/efficacy and based on early clinical reports it looks like disulfiram may be a game changer. It is no wonder thousands of patients are sharing their experiences in social media.

I just want patients to get proper care working with a trained physician.