Consolidated Baclofen Information Thread

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

Information about HDB related to safety and efficacy:

terryk;1112163 wrote: and this one:

High-dose oral baclofen: experience in patients with multiple sclerosis.

Smith CR, LaRocca NG, Giesser BS, Scheinberg LC.

Neurology. 1991 Nov;41(11):1829-31.

PMID:
1944915
[PubMed - indexed for MEDLINE]

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

Safety/SEs/Dosing

More from the man who has forgotten more than I will ever know:

terryk;1115380 wrote: Some extracts (and commentary by me) from Clinical and pharmacokinetic aspects of high dose oral baclofen therapy (emphasis mine):

On the safety and possible side effects of high-dose (up to 300mg /day) baclofen:


“A recent trend among clinicians is the use of high-dose baclofen (80 to 300 mg/day) to control severe spasticity in patients with multiple sclerosis (MS) or spinal cord injury (SCI) when it does not respond to conventional dosages.”

“Side effects presumably due to baclofen were reported by five patients. These included transient muscle fatigue, hypotension, mild sedation, lightheadedness, and nausea. In most cases, symptoms resolved without change in baclofen dose. Although no toxic level applicable to all patients was found, levels beyond the tolerance of individuals were defined.”

“There was a strong correlation […] between incidence of possible side effects and patient age.”

“In this study, ten of eleven patients received higher doses of baclofen than the 80 mg daily maximum recommended in the 1992 Physicians’ Desk Reference. […]. Although side effects occurred in five patients, they tended to be mild, developing most often in older patients.”

“Clinical experience has shown wide variations in effective baclofen dosages among individuals, and it is often necessary to use doses that signigicantly exceed 80mg/day to achieve adequate symptomatic relief of spasticity. In our study, such doses were generally safe and effective, with a tendency for side effects to occur in older patients.”



On large individual doses of baclofen (like a whole handful or day’s worth of pills at once):

“Baclofen has been demonstrated to stimulate gastric motility in the rat, suggesting that larger doses of baclofen may be less well absorbed.”



On the sometimes unexpected non-linear blood levels of baclofen in patients:

“An earlier study suggests that baclofen levels can diminish with time on a stable dose. Our data demonstrated increasing blood levels over time in three of five patients on a stable regimen which ranging [sic] from 120 to 240mg/day.”

A large part of the article discusses the phenomenon observed in this study of a non-linear relationship with baclofen dosing and baclofen blood levels, in several patients. To put it in simple terms, one would expect that after ingesting a drug, the drug would be absorbed in to the body, achieve a peak blood level, and then that level would diminish as time went on and the body metabolized/excreted the drug. The process would repeat with each successive dose. It was observed in this study, however, that this did not always happen. In one case, a patient’s kidneys did not excrete the baclofen as efficiently as they should have. The patient’s baclofen-blood level kept increasing (and she actually enjoyed the benefit of increased relief from spasticity) until it caused her blood pressure to drop too low. The article goes on to explain other aspects of , and possible reasons for, this phenomenon. It gives me food for thought as to why folks here are reporting all kinds of differences in ability to titrate up and present/cope with side effects.





And finally for your amusement…

“The major portion of a dose is recovered in the urine in amounts ranging from 50 to 80 percent.”

Yup, I knew that most of the baclofen dose that you take leaves the body unchanged (15% is metabolized by the liver the other 85% is filtered by your kidneys), but it wasn’t until I read that sentence that a light-bulb went off in my head.

You could theoretically drink your own (baclofen-fortified) urine to stave off withdrawal in emergency baclofen shortages. (I had a funny side note here, but I edited it out on second thought).
-tk

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

tk- I'll remove those posts if you want to transfer them over yourself.
Would you be so kind as to provide a brief synopsis of the first two posts, much as you did with the last. This stuff is Greek (or rather, Latin) and I was WAY too out of it when I first got here to figure it out without help. (Still need help, but not for the same reason! Now it's just very evident that I'm no scientist. Yet.)

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

Dose dependence of effectiveness

Last one for me today, folks. I think I started on page 25 of the old thread, and left off on page 29, if anyone else wants to explore and transfer valuable information.
Hope it's a good bac-filled, boozeless day! (for the bac-ers and the same minus the bac for the non-bac-ers.)

Ne/Neva Eva;1119055 wrote: brand new article, sent courtesy of Dr. OA. (Thank you!)

I will post the link when I figure out how to do it!

From Science Magazine:


NEWS&ANALYSIS
ADDICTION RESEARCH
Anonymous Alcoholic Bankrolls Trial of Controversial Therapy
Ameisen says dosing is crucial. Another study by Addolorato?s group published in April showed that alcoholics who take 60 milligrams of baclofen do better, sug- gesting that 30 milligrams is below the optimal dose. Ameisen says both 30 and 60 milligrams are ?ridiculously low:? Neu- rologists who use the muscle relaxant to treat spasms have long treated patients with up to 300 milligrams daily without serious side effects except sleepiness, he says.
But other scientists say it?s prudent to be careful with a drug whose side effects have not been studied systematically. The U.S. Food and Drug Administration?s limit for treating spasticity is 80 milligrams. The Amsterdam study now on the drawing board will escalate the dose while carefully mon- itoring patients, Wiers says; the research- ers might put the study?s ceiling at 150 or
200 milligrams. Others say that?s quite high. Garbutt has proposed a new trial that would go up to 90 milligrams a day, which is ?already pretty aggressive,? he says. Addo- lorato says he would not go beyond 100 milligrams.
Ameisen is frustrated with the slow pace of research, but his zeal to convince the world is rubbing some the wrong way. ?When people know all the answers before having the data, it?s usually not worth listening to,? Heilig says. Nor has Ameisen?s treat- ment of skeptics?in interviews with Science, he described several scien- tists as ?stupid??made the cardiol- ogist any friends. An adviser to the Amsterdam study, Ameisen says he?s already disappointed in the commu- nication with Wiers?s team. That may be because he often fires off multiple
AMSTERDAM?For 6 years, French cardiolo- gist Olivier Ameisen has tried to persuade addiction researchers to set up a large clinical trial of what he claims is a safe and highly effective cure for alcoholism: high doses of a decades-old muscle relaxant called baclofen.
Ameisen?s main argument: his own case. There was a time when he could down a bottle of Scotch a day and, in his bestsell- ing 2008 book The End of My Addiction, the cardiologist describes how baclofen broke that habit and saved his life.
Now, Ameisen may finally get the study he wants. As a gesture of thanks to Ameisen, a Dutch donor has given the University of Amsterdam half-a- million euros to conduct a rigorous placebo-controlled study of the drug,
to be led by psychopathologist and addiction researcher Reinout Wiers. The philanthropist?s name is being kept secret, but Ameisen, who met him at a lecture, says the man was a ?hopeless alcoholic? until he gave his physician a copy of Ameisen?s book and received baclofen.
The study could help settle what Markus Heilig, clinical director of the National Institute on Alco- hol Abuse and Alcoholism, calls a ?controversy in a low-key way.? Ameisen?s advocacy for baclofen? which mimics the action of a neurotransmitter called gamma- aminobutyric acid (GABA) in the brain?has generated a lot of publicity, and increasing numbers of alcoholics demand a prescription from their doctors. But hard evidence for its efficacy has been lacking. A handful of trials have generated conflicting evidence; all were small and used much lower doses of baclofen than Ameisen recommends. The anonymous gift is a ?fantastic opportu- nity,? says alcoholism researcher Giovanni Addolorato of Catholic University of Rome.
A successful cardiologist working in Manhattan, Ameisen saw his life and career coming apart in the 1990s, when his binges frequently landed him in the emergency room. Highly motivated to kick his habit, he tried all sorts of treatments, attended thousands of Alcoholics Anonymous meet- ings, and checked into rehab centers. Yet he always relapsed. Then he read a story about
baclofen, a drug that in animal models of alcoholism appeared to suppress craving. He devised a study protocol in which he took escalating doses of baclofen. At 270 milligrams a day, he wrote in a rare first- person case study published in a 2005 issue of Alcohol and Alcoholism, ?I experienced no craving or desire for alcohol for the first time in my alcoholic life.? He still takes lower doses of baclofen daily to keep his anxiety in check and hasn?t taken a drink since 2003.
Scientists believe that GABA may play a role in addiction, and another drug can-
Craving evidence.
In a book about his recovery (inset), Olivier Ameisen urged scientists to do clinical trials
of baclofen.
didate for alcoholism, topiramate, also tar- gets the GABA receptor (Science, 11 April 2008, p. 168). The anecdotal stories about miraculous recoveries with baclofen extend beyond addiction to alcohol to people with cocaine and other drug problems. The few randomized controlled trials?the gold standard in medicine?have shown mixed results, however.
In a study among 84 heavy drinkers with liver damage, published in The Lancet in 2007, Addolorato showed that 30 milli- grams of baclofen a day helped 71% abstain from drinking, versus 29% of those on pla- cebo. But in a 2010 study of the same dose among 80 diagnosed alcoholics by James Garbutt of the University of North Caro- lina, Chapel Hill, baclofen did not outper- form placebos.
long e-mails per day, Wiers counters. Yet even those who are skeptical about baclofen, such as Heilig, applaud the new study because it may help bring doctors and patients some answers. The study will aim to enroll at least 200 diagnosed alcoholics, Wiers says, and will also aim to find out whether the drug is most effective in peo- ple also suffering from anxiety disorders, as some studies suggest. Functional mag- netic resonance imaging will help estab- lish whether the drug affects brain circuits
involved in anxiety. Wiers is ?a highly respected investiga-
tor in the field of alcohol dependence,? says Lorenzo Leggio of Brown University?s Cen- ter for Alcohol and Addiction Studies. ?I am sure it will be a very good study.?
?MARTIN ENSERINK
Science SCIENCE VOL 332 6 MAY 2011 Published by AAAS
653
CREDITS (LEFT TO RIGHT): ?FRANCK FERVILLE; COURTESY FARRAR, STRAUS AND GIROUX
Downloaded from Science on May 6, 2011

[terryk]

Consolidated Baclofen Information Thread

Ne/Neva Eva;1211286 wrote: More from the man who has forgotten more than I will ever know:

I haven't forgotten.

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

terryk;1211319 wrote: I haven't forgotten.

hmmm. You forgot that there was a new and improved CBT and continued to post on the old one. Smarty pants. Don't worry. I'll be around to remind you where you can put your endless wealth of knowledge.
:l
Thanks for all of it.

[redhead77]

Consolidated Baclofen Information Thread

Sorry, post deleted. I think I should just stay out of the brain threads. I kind of missed some important points here. Remember, I do suffer from ADD. :H Ne, thanks for posting the study, tk originally found. Tk, I hope you'll do a synopsis for us.

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

Yo! I got a malware warning from one of the journal entries on the first list, Lo0p. It's this link:

http://www.urbanfool.us/MWO/newdrug.pdf

[Ne/Neva Eva]

Consolidated Baclofen Information Thread

Also in the link to the Aldorato's Lancet article. bummer. And I'm late to meet with a new doctor! oy.

Mx, can you use your internet superpowers to check that out?

[Cassander]

Consolidated Baclofen Information Thread

Lo0p;1182074 wrote: Wow! Nice find!

Here is the full version PDF: http://dl.dropbox.com/u/15371700/Alc...rato-312-7.pdf

I'll edit it in when I can.

Hey Lo0p--

Here's another one to edit into the Consolidated Thread when you have a chance.

Effectiveness and safety of b... [CNS Neurol Disord Drug Targets. 2010] - PubMed - NCBI

Thanks,

Cass

[Lo0p]

Consolidated Baclofen Information Thread

With all due respect, Cassander, isn't it just a student's paper?

I am still looking for someone with the ability to start up a website where quite a few of us would have control as to the content and uploads and such. I alone can't even keep my own piddly consolidated thread updated.

If you are that person, please step up up!!!

[Lo0p]

Consolidated Baclofen Information Thread

Oops! Nevermind! I thought you were talking about that paper you found before I even clicked on the link!

edit: I'll see if I can find the full one real quick, but I've got to rush off to work early today.

edit edit: I'm having problems with my Johns Hopkins VPN, but I'm picking up my PhD student friend who's account it belongs to tonight at the airport after work! :happy: So I'll be able to check into it soon. Busiest time of the year for me work and family wise though. :argh:

[Cassander]

Consolidated Baclofen Information Thread

Hey Lo0p

Yep its the new Leggio/ Garbutt /Addolorato paper I was referring to which I think is really pretty good and pretty important. Worthy of the Consolidated thread, I think...

Here's another link to it

Bentham Science Publishers

If you go to this page and click on "View" you can easily get a pdf, but I was not able to upload the pdf to my post. Stymied.

I get it about your busy time of year and I agree it would be nice if some webmaster type would step up to the plate. Maybe webmasters don't drink?

Best,

Cass

[Cassander]

Consolidated Baclofen Information Thread

bump for newbies and lurkers
this is a great place to start learning about baclofen if, for example, you have some New Year's Resolutions in mind...

[Mirawizad]

Consolidated Baclofen Information Thread

Baclofen Benefits

For a balanced view, I would like to see the Baclofen Benefits listed on the main page right next to the adverse reactions link -

https://www.mywayout.org/community/f2...its-45389.html