The Efficacy of Baclofen in Reducing Alcohol Consumption

[Cassander]

Here is a link:

http://commons.pacificu.edu/cgi/view...195&context=pa

to an interesting summary prepared by a physician's assistant student in 2010 of the studies which have been conducted until then regarding the efficacy of baclofen in treating alcoholism.

I think all of the studies summarized in the report have been published and are generally known, but this article is useful because it summarizes the literature in one place.

[Greg]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Thanks for posting this. It seems well researched and written. Hopefully in time there will be a lot more research conducted on baclofen treatment of alcohol dependence, although the lack of financial incentives for pharmaceutical companies is an unfortunate problem.

Maybe one of them could come up with an extended/slow-release formulation of it, and make money from that as a treatment for alcohol dependence...I'm pretty sure that has already been suggested by one or two other people here.

[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Slow release baclofen

Greg;1224917 wrote: Maybe one of them could come up with an extended/slow-release formulation of it, and make money from that as a treatment for alcohol dependence...I'm pretty sure that has already been suggested by one or two other people here.

Yes it has, by a number of people... including me....

So I googled slow release baclofen (again) and discovered that some researchers in India have found that a single dose of slow release baclofen has the same efficacy as multiple doses of immediate release baclofen, with fewer side effects, albeit for the treatment of spasticity.

Here's the link:

http://www.neurologyindia.com/articl...;aulast=Sampat

[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Here is a link to another compilation of the research to date prepared in Germany, published in June 2010 and titled "Baclofen zur Behandlung der Alkoholabh?ngigkeit":

PsyCONTENT - Journal Article

Unfortunately, you need to pay for the entire article, which is written in German, but here is an English-language abstract:

Aims: This review summarizes the current state of knowledge about baclofen as a treatment for alcohol dependence, taking into account preclinical and clinical findings. Method: A systematic literature search using the medical database PubMed was conducted. The following keywords were used: baclofen, alcohol dependence, craving, treatment, pharmacotherapy, relapse prevention. Results: Both in preclinical and clinical trials, there is first evidence for the efficacy of the GABAB receptor agonist baclofen in the treatment of alcohol dependence. Different open and single-blind studies reported that baclofen was able to reduce alcohol withdrawal symptoms with good tolerability. Furthermore, the findings of several open and two randomized controlled trials suggest that the use of baclofen for relapse prevention is effective and safe. In addition, baclofen led to a reduction of anxiety in alcohol-dependent patients. However, a larger controlled study in the United States did not confirm these results, so that further studies are urgently needed. Conclusions: Baclofen is a promising agent for the extension of the currently available pharmaceutical treatment options for alcohol-dependent patients. However, further studies are required to clarify important questions regarding efficacy and tolerability, and to define the dosage with the most favourable risk-benefit profile as well as responding patient subtypes.

[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Effectiveness and safety of baclofen in the treatment of alcohol dependent patients.

Here is an extraordinary MUST READ article written by three of the leading baclofen researchers in the US and Europe which was published in Volume 9 Issue 1 of CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) in 2010.

The article summarizes ALL of the research conducted to date on the effectiveness and safety of baclofen for alcoholism.

A pdf of the entire article can be downloaded from Bentham Science Publishers on this page: Effectiveness and safety of b... [CNS Neurol Disord Drug Targets. 2010] - PubMed - NCBI


Here is the abstract:

CNS Neurol Disord Drug Targets. 2010 Mar;9(1):33-44.
Effectiveness and safety of baclofen in the treatment of alcohol dependent patients.
Leggio L, Garbutt JC, Addolorato G.
Source

Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA. Lorenzo_Leggio@brown.edu
Abstract

Both preclinical and clinical research studies have shown the GABA(B) receptor agonist baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that baclofen is able to suppress withdrawal symptoms in alcohol-dependent patients affected by the alcohol withdrawal syndrome. Moreover, baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. These trials also demonstrated that baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving. However, more work is needed to clearly demonstrate the efficacy of baclofen and to ascertain whether efficacy is limited to certain subtypes of alcoholic patients. For example, a recent US trial failed to demonstrate a robust effect of baclofen in treating alcohol-dependent patients though the relative moderate severity of alcohol-dependence in that trial has been suggested as one factor that may have contributed to the finding. In the present review, the authors will summarize the published clinical studies on the role of baclofen in alcohol dependence and will also present some unpublished secondary analyses. Finally, the authors will discuss possible future directions to further investigate the role of baclofen in alcohol dependence (e.g., baclofen's biobehavioral mechanisms, different baclofen doses, differences in severity and in alcoholic subtypes, different formulations of baclofen, possible combination of baclofen with other medications).

The article concludes:

The overall findings from studies performed to date indicate that baclofen represents a promising new pharmacotherapy for the treatment of alcohol dependence.

First, baclofen represents an interesting medication because of its role in reducing withdrawal symptoms as well as in reducing alcohol drinking and craving, thus promoting alcohol abstinence.

Second, baclofen has displayed a very safe profile, with the lack of serious or severe side-effects.

Third, baclofen has also been shown to be a manageable drug, without any potential of abuse, a feature of paramount importance when administering a medication to an addicted population.

Future studies involving larger number of patients should be conducted to confirm the present findings, as well as to identify the best subpopulation of alcoholics which is more likely to respond to treatment with baclofen.

Studies testing higher doses of baclofen, its combination with other medications, as well as laboratory studies aimed at elucidating the biobehavioral mechanisms of baclofen are also of importance.



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[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

I spent much of last night and this morning reading Effectiveness and Safety of Baclofen in the Treatment of Alcohol Dependent Patients by Leggio, Garbutt and Addolorato.

This study appears to be the most comprehensive analysis of the research regarding baclofen for use in treating alcoholism to date. The fact that it is authored by these three men is important since they have been involved in almost all of the clinical studies of baclofen for alcoholism over the past 10 years. Together with Ameisen they have been at the forefront of baclofen research.

While the article calls for more research to confirm efficacy, to resolve some uncertainties and to further understanding of how baclofen works, in general it strongly supports the hypothesis that baclofen is both safe and effective for treatment of alcoholism. It finds that the animal and human studies to date support the efficacy of baclofen and find no evidence that the drug is unsafe or addictive, even at higher doses.

It concludes as follows:

The overall findings from studies performed to date indicate that baclofen represents a promising new pharmacotherapy for the treatment of alcohol dependence.

• First, baclofen represents an interesting medication because of its role in reducing withdrawal symptoms as well as in reducing alcohol drinking and craving, thus promoting alcohol abstinence.
• Second, baclofen has displayed a very safe profile, with the lack of serious or severe side-effects.
• Third, baclofen has also been shown to be a manageable drug, without any potential of abuse, a feature of paramount importance when administering a medication to an addicted population.

Future studies involving larger number of patients should be conducted to confirm the present findings, as well as to identify the best subpopulation of alcoholics which is more likely to respond to treatment with baclofen. Studies testing higher doses of baclofen, its combination with other medications, as well as laboratory studies aimed at elucidating the the biobehavioral mechanisms of baclofen are also of importance.


For those with a little more time and/or interest here is a summary of the article.

The authors state that the animal studies which have been conducted to date support the hypothesis that baclofen can suppress withdrawal signs and can reduce both alcohol drinking and alcohol seeking behaviors.

They review the reported studies which indicate that baclofen might represent an effective medication in the management of alcohol dependent patients affected by alcohol withdrawal (AWS). They say that larger studies are needed to investigate the ability of baclofen in preventing and treating more serious AWS complications (i.e., DTs, seizures).

They review a number of so-called open-label (no placebo) baclofen trials which have been conducted and state that “the primary value of these open-label trials has been to show that baclofen administration to alcoholic patients is both feasible and generally well tolerated. The improvements in drinking behavior, anxiety and craving are suggestive of efficacy and, along with the reported effects on alcohol withdrawal symptoms, raise the possibility that levels of anxiety, craving and/or alcohol withdrawal symptoms represent targets to identify baclofen efficacy.”

There have been a small number of placebo-controlled trials which the authors state strongly indicate that baclofen has efficacy in alcohol dependence. They report that baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. They say that these trials also demonstrated that baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving, but call for more work to clearly demonstrate the efficacy of baclofen and to ascertain whether efficacy is limited to certain subtypes of alcoholic patients.

In particular, they note that a recent US trial failed to demonstrate a robust effect of baclofen in treating alcohol-dependent patients. They observe that the relative moderate severity of alcohol-dependence in that trial may have been a factor that have contributed to the finding. They also observe that differences in patient populations, e.g. severity of dependence, treatment goal, may explain the variations in outcome across trials.

With respect to safety and “manageability” they observe that baclofen has been employed for years as a particularly manageable and safe antispasticity drug. Thery state that none of the clinical studies investigating baclofen efficacy in alcohol dependence have shown a problem with manageability or any serious or severe side effects. They observe that the manageability and safety of baclofen in the treatment of alcohol dependence is also supported by two case reports (one of which is Ameisen’s) on the suppression of alcohol consumption achieved with high doses of baclofen.

With respect to “tolerability” they concluded that tolerability was fair in all baclofen-treated patients. They noted a fair degree of tolerability in patients previously treated with baclofen who subsequently required a new cycle of baclofen for a sudden episode of alcohol craving; none of these patients displayed severe side effects or reported drug-induced sedation and all continued their usual daily activity. Finally, they report that no patient treated with baclofen reported mood dysfunction, dysphoria, euphoria or other pleasurable effects or any degree of craving for the drug.

On discontinuation of baclofen, no drug withdrawal syndrome and/or side effects due to drug suspension have been observed. The absence of serious side-effects was also noted in cocaine dependent patients and in certain nicotine dependent patients.

They note that the administration of baclofen in alcohol dependent individuals has been shown to be safe even when administered to alcoholics who had severe liver damage. However, they do call for long-term trials to confirm these results with cirrhotic alcoholics. They observe that the absence of hepatotoxic effects could be related to low liver metabolism of baclofen, which is mainly excreted unmodified by the kidney. No renal side-effects were recorded. In summary, they conclude, baclofen has been shown to be safe in alcohol-dependent patients with cirrhosis, at least in those without kidney diseases, hepatorenal syndrome, or both.

Overall, they conclude, the preponderance of human studies indicates the efficacy of baclofen for reducing alcohol intake and craving. Moreover, the suppressing effects exerted by baclofen on craving for alcohol and drinking during AWS identify baclofen as a promising and unique pharmacotherapy for use in the treatment of alcohol dependence.

They go on to say that baclofen is of particular interest in view of its efficacy on several aspects of the disorder, namely AWS, anxiety and maintenance of abstinence. These properties of baclofen, if confirmed, could result in a simplified pharmacotherapy of alcohol dependence and higher compliance to treatment.

They state that pharmacotherapies for alcohol dependence could have beneficial effects on long-term abstinence and reducing drinking through a variety of biobehavioral mechanisms, such as: i) attenuating urges to drink during abstinence that might otherwise elicit alcohol-seeking behavior and lead to relapse; ii) decreasing attention to alcohol cues that might lead to relapse, especially after repeated exposures to alcohol cues; iii) attenuating some of the positive reinforcing (pleasurable) effects of alcohol that an alcoholic may experience if the subject takes a drink; iv) increasing some of the negative (aversive) effects of alcohol that might be experienced if an alcoholic takes a drink; v) decreasing negative consequences of prolonged consumption such as anxiety that can act as triggers for relapse.

They mention other pharmacotherapies being studied and report that the biobehavioral mechanisms mentioned above have been studied for naltrexone, acamprosate and topiramate. They report that human laboratory studies have shown that naltrexone reduces urge to drink and attention to the alcohol cues during alcohol exposure. Studies with alcohol self-administration after an initial drink demonstrated that naltrexone-treated subjects drink fewer drinks and report lower levels of alcohol craving during the self-administration of alcohol, especially if the self-administration is delayed, instead of being right after the initial drink. Other human laboratory studies showed that acamprosate attenuates the subjective alcohol craving induced by a priming drinking and that topiramate exerts its beneficial effects by altering the subjective experiences of alcohol consumption. They observe that such biobehavioral mechanisms have not as yet been investigated in human laboratory settings for baclofen though such studies could prove very informative. They observe that the combination of baclofen with other medications helpful in treating alcohol dependent individuals represents another aspect to be investigated and that animal studies have shown the potential utility of the combination of baclofen and naltrexone in the treatment of alcohol dependence. Although the rationale to test this combination in humans has been highlighted, no clinical data are currently available. A randomized, double-blind, placebo-controlled pilot study is currently in progress (study registered with ClinicalTrials.gov, number NCT00614328).

Lastly, they touch on research regading dosage and release mechanisms. Baclofen is currently available as an immediate release (IR) formulation. They report that two modified formulations, baclofen sustained release (SR) and gastric retentive system (GRS), have been proposed to be equivalent in efficacy to baclofen IR with the administration of a single daily dose. They cite a recent study conducted in patients with chronic neurogenic muscular spasticity showed that once-daily baclofen SR and GRS are efficacious, convenient, and better tolerated alternatives to baclofen IR in patients with neurogenic spasticity. They also report that a pharmaceutical company, Alkermes, is currently conducting a phase 1, open-label study aimed at comparing the pharmacokinetic profile of the currently used formulation of baclofen (immediate-release; 30 mg) with a new extended released formulation of baclofen 30 mg (study registered with ClinicalTrials.gov, number NCT00802035). The use of an extended formulation of baclofen in treating alcoholics has not yet been explored. Potentially, such formulations might have the benefits of reducing possible side-effects and improving compliance to the medication.



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[missyabby1]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Yeah Cass

Thanks Cass

Missy xx


t

[suneelca]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Cassander -- many thanks for this. What's interesting to me is that this might get even more traction -- in terms of getting the neurologists and neurobiologists interested in pursuing research on Baclofen -- is if it's pitched as alleviating underlying anxiety, rather than reducing / eliminating alcohol abuse and dependence. At a more basic level, that Baclofen remediates amydala dysfunction. That's the kind of stuff that turns these folks on. Alcoholism as a potential expression of an underlying neurochemical / neurochemical disorder. Other expressions can include alleviating some symptoms of autism, as I think I read about in another thread.

I'm sure you covered this in the other thread about Baclofen and anxiety, Cassander. I just Googled Baclofen and anxiety again, and I came up with nothing in terms of published studies. Only message board posts and threads, many or most from here! Then just Googled Baclofen and amygdala, and came up with studies from 1992 and 1994 on the effect of Baclofen on 'amygdala kindling' in rats. As I recall, these are studies that Dr. Amiesen cited in his book(s).

As have indicated, am going to bring Baclofen to the attention of my brother, who is a neurologist who runs a research institute focusing on rehabilitative neuroscience. He knows that I've had problems with drinking over the years, so I don't have a problem availing him of that. That said, perhaps our pushing the research community to look at Baclofen and get NIH grants to study it is a matter of positioning. If we position this as research to determine the effect of Baclofen on anxiety and the amygdala, rather than on alcoholism per se, would that make them more likely to want to look at it?

Either way, am going to impress on my brother, as well as my MD shrink who originally recommended Baclofen to me, that it is borderline criminal to not drive further research on a compound that can potentially have such a profound effect on the lives of so many suffering people.

[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

suneelca;1225266 wrote:
As have indicated, am going to bring Baclofen to the attention of my brother, who is a neurologist who runs a research institute focusing on rehabilitative neuroscience.

Hi Sune

Here is a link to a page where I was able to download the entire article. Hopefully it will work for you. (I tried to attach the entire article to my post, but mwo informed me that the document exceeds mwo's size restrictions).

You will see that there are extensive references, including some to the underlying neuroscience. Perhaps you could give your brother a copy of the article with references...

Bentham Science Publishers

Cassander

[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Ok. Why (you might ask) is this article so important? Here is my interested but layman's answer:

1 It is authored by three extensively published researchers who have been engaged in alcoholism research for many years. Addolorato has co-authored at least three studies on baclofen over the past 10 years. His was one of the studies which Ameisen used to support his investigation. Garbutt was a co-author of the (low dose) US study which did not establish efficacy, but as this study acknowledges, did not disprove efficacy either. This report suggests that there may have been some explanations why the US study was not as robust as might have been predicted. I think it is telling that Garbutt is co-authoring this report, notwithstanding the results of his earlier study.

2 The article surveys all of the literature and finds no meaningful failures of hypothesis. There is still much to be definitively established but there are no game stoppers.

3 As we have seen here, the article acknowledges a connection between anxiety, alcoholism and baclofen. It suggests follow up in this area.

4 The article acknowledges that high dose baclofen may be warranted in certain cases and calls for testing at higher dose levels.

5 The article finds no evidence that baclofen is unsafe or addictive.

6 The article suggests that the side effects are safe, tolerable and manageable.

7 The article suggests that with more testing there may be more positive developments, including in the areas of time release doseage and combination of medications to obtain even better results.

I think the article supports Ameisen's conclusions, but is more compelling since it is not a self-report and surveys a broader history than was available to Ameisen. It also suggests to me that additional work is being done (while we wait). I took a look at Leggio's bio at Brown University and, among other things, he is currently working on A Double-Blind, Placebo-Controlled, Randomized Human Laboratory Pilot Study of Baclofen in Anxiety Disorders with Comorbid Alcohol Dependence. Here's a link: The Directory of Research and Researchers at Brown: Lorenzo Leggio

I know this isn't the definitive double blind study that is so desperately required before there is broad acceptance of baclofen in the medical community, but it is very positive, nonetheless.



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[RudyB]

The Efficacy of Baclofen in Reducing Alcohol Consumption

really great stuff here, cassander. thank you so much for compiling and distilling and putting so much work into this, it is so helpful and encouraging to read. thanks for sharing it with we who need and value it most.

[bleep]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Thanks for your hard work here Cassander, much appreciated.

I'll go through these when time permits, your summaries will prove very helpful!

[Cassander]

The Efficacy of Baclofen in Reducing Alcohol Consumption

bleep;1225944 wrote: I'll go through these when time permits...

Bleep, pls do look carefully at the Leggio/Garbutt/Addolorato article. Its the best summary I have yet seen of where the research is (and isn't) and I think its a pretty good indicator of what the scientific community (atleast in the guise of these three very knowledgeable researchers) thinks about all of this.

In many ways I think that some of you on this board know as much as anyone in the world about HDB, but we also know the medical community will not embrace HDB until the science is established. I think this article tells us where the science is (or was when the article was prepared in 2009).

I would love to hear your reactions to it. As I would the rest of the board's.

Thanks, Cass

[Greg]

The Efficacy of Baclofen in Reducing Alcohol Consumption

Cassander;1224964 wrote: So I googled slow release baclofen (again) and discovered that some researchers in India have found that a single dose of slow release baclofen has the same efficacy as multiple doses of immediate release baclofen, with fewer side effects, albeit for the treatment of spasticity.

Here's the link:

Once daily baclofen sustained release or gastro-retentive system are acceptable alternatives to thrice daily baclofen immediate release at same daily dosage in patients Sampat NG, Kulkarni RV, Sase N, Joshi NH, Vora PB, Bhattacharya AK, Lakhani JD, B

I'm a bit late in replying, but wanted to say thanks for including this and other information.

[c0ffee]

The Efficacy of Baclofen in Reducing Alcohol Consumption

cassander, what borough do you live in?