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Dutch Baclofen trial on Twitter

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Stot

Did anyone read this article that was posted on Twitter. It's quite clear that the study had many flaws but an interesting read all the same.  The funding sources make it all a bit suspect too. 

Edited by Stot
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Molly78

The alcohol intake in the participants was surprisingly low - why would any female who drinks 14 units a week want to be part of a trial aimed at reducing alcohol intake?

Why do the funding sources make it suspect?  I couldn't see that the funding came from Big Pharma, which would make it suspect!

Thank you for posting that - all studies are of interest on this site.

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Baclofenman

Hi Stot

As you rightly suggest the "trial" has many flaws

Firstly, it is a trial to compare the differences on alcoholism between three groups, one taking high dose Baclofen, one low and the other, a placebo

The main problem I have with this trial, if you can call it a trial is that only 15% of the 58 participants assigned high dose Baclofen managed to get to the 150 mg per day that was the maximum target dosage 

Further more with a mean average of 90 (something) mg per day this means a considerable amount of participants failed to meet 80 mg per day, which IMO is where "high dose Baclofen" comes into play - I have not seen the actual individual figures but it is likely that in excess of 50% failed to get to 80%, yet their results are included in the high dose Baclofen statistics - There is no way I would consider >30 mg a day to be high dose Baclofen - I also think the titration (10 mg every other day) was too steep and this lead to excess drop outs due to the side effect rapid titration can cause

So, of course if 85% of people fail to make the maximum design dosage, the trial is flawed, pointless - I have other issues with the trial as a whole but this means it does not get past the first hurdle

Unfortunately, unless one actually looks at the nuts and bolts of any given trial they are turned by the headline makers who generally are after the glory rather than the content - Rather like our friend, over there

Regards

 

Bacman

Edited by Baclofenman
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Otter

I was sent this article a while ago.  I don't think I have seen it posted anywhere.  Here is the abstract:

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High-dose baclofen for the treatment of alcohol dependence (BACLAD study): A randomized, placebo-controlled trial

Christian A. Müller  Olga Geisel, Patricia Pelz, Verena Hill, Josephine Krüger, Anna Sticker, Anne Beck, Klaus-Dieter Wernicke, Rainer Hellweg, Andreas Heinz

Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30–80 mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30–270 mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence.

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Otter
On 12/14/2016 at 11:28 PM, Baclofenman said:

Hi Stot

As you rightly suggest the "trial" has many flaws

Firstly, it is a trial to compare the differences on alcoholism between three groups, one taking high dose Baclofen, one low and the other, a placebo

The main problem I have with this trial, if you can call it a trial is that only 15% of the 58 participants assigned high dose Baclofen managed to get to the 150 mg per day that was the maximum target dosage 

Further more with a mean average of 90 (something) mg per day this means a considerable amount of participants failed to meet 80 mg per day, which IMO is where "high dose Baclofen" comes into play - I have not seen the actual individual figures but it is likely that in excess of 50% failed to get to 80%, yet their results are included in the high dose Baclofen statistics - There is no way I would consider >30 mg a day to be high dose Baclofen - I also think the titration (10 mg every other day) was too steep and this lead to excess drop outs due to the side effect rapid titration can cause

So, of course if 85% of people fail to make the maximum design dosage, the trial is flawed, pointless - I have other issues with the trial as a whole but this means it does not get past the first hurdle

Unfortunately, unless one actually looks at the nuts and bolts of any given trial they are turned by the headline makers who generally are after the glory rather than the content - Rather like our friend, over there

Regards

 

Bacman

The main problem with this trial is with the way in which participants were selected.  They had all completed a counselling based rehab.   I expect that if one looks at the rehab treatment they received, they were all expected to be abstinent when they entered the program of rehab. This means they had been able to stop drinking many weeks before the trial.  

Having stopped drinking already, I do wonder what the point of the trial was.  Baclofen is for those who are unable to stop on their own.  These people were low level alcoholics, if that means anything at all

 

My problem with all the research is that it all weeds out those alcoholics who are too ill to self-administer baclofen on their own.  Some studies have tried to get participants who are at the more serious end of the addiction but the problem there continues to be that they may be unable to keep up the dosage schedule and may show a poorer outcome because of their inability to keep to a dosage schedule.

 

There are a number of other issues which make trials unreliable.  One is that entrance into the trials is based on self-describing of alcoholics as being alcoholic and the degree to which they are affected by the illness. This makes the entire trial entirely subjective in terms of the seriousness of the illness in the participants.  The results also rely on self-reporting of the effects of both baclofen and placebo so there is the risk that those on placebo are reporting better results than they achieved because of a psychological desire not to have failed.  

This study simply shows that where baclofen is given to those who are able to control their own drinking without medication, baclofen doesn't add anything.  Going to a higher level would not be medically indicated, would it? Why would you increase dosage for someone who hasn't been drinking at the beginning of a trial?  This appears to be a trial which uses baclofen to prevent relapse, which is not what it is intended for or why it is a remarkable drug.  It isn't, surely, of much significance that this type of "alcoholic" isn't aided by the unnecessary administration of baclofen to curb cravings which have already been checked adequately by psychosocial counselling.  

 

One way of getting more consistent results which can be compared to other trials would be to use a scientific test to determine both who participates and what the results say.  Blood tests and liver tests come to mind.  I'm no expert in that but in summary, I don't think this particular trial was well thought out and the criticisms of it say the same thing.  Seems to me to have been a waste of money and not at all helpful in determining whether baclofen should be prescribed for those with serious, chronic alcohol problems.

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Molly78
3 hours ago, Otter said:

 This appears to be a trial which uses baclofen to prevent relapse, which is not what it is intended

I thought that's how Ameisen used it?  He wasn't a daily drinker, he could go for 3 months at a time without drinking, but always relapsed before he took baclofen, if I'm remembering his account correctly.

It's only on here & MWO that I've read about people drinking 2 bottles of wine a day while titrating up.

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Otter
8 hours ago, Molly78 said:

I thought that's how Ameisen used it?  He wasn't a daily drinker, he could go for 3 months at a time without drinking, but always relapsed before he took baclofen, if I'm remembering his account correctly.

It's only on here & MWO that I've read about people drinking 2 bottles of wine a day while titrating up.

Aha!  

I have to admit that my experience of alcoholics is of people who drink every day from morning until night. I had relatives, a work colleague, my wife and many clients who were alcoholics and they were unable to stop for any length of time, not even a day.  

It does seem I must be at cross purposes.  I think it comes back to how we define this illness.  

Molly, I certainly did not read Ameisen's book and think he was drinkng occasionally. He portrayed himself as a daily drinker who could not stop.  That was the whole point of the book.  He was simply unable to stop, ever.

 

I think the problem is that you haven't experienced daily out and out falling down alcoholism as I have with my wife.  I think you would be shocked to realize how serious this can be.  

I think you must imagine Ameisen to have been drinking sporadically because you can't conceive of someone drinking a litre of Vodka every day from six in the morning and spending three out of every four weeks in bed.  I think in the end Ameisen had to give up work because he was just shot away.   You may recall that when he left rehab he began drinking immediately, on the journey home.

I have to say that your post has been a revelation.  I wonder if the sceptics of baclofen realize that it works in cases such as my wife's where someone is drinking a litre of spirits a day.

 

When I was in contact with Dr Heydtmann we discussed Dr Chick and he said that Chick's patients were different from his own.  Heydtmann had terminal cases of liver disease.  I spoke to him about about their drinking habits and he was not surprised by the level of my wife's drinking.  It was typical of his patients.  Chick had a middle-class private professional clientele.  He is less committed to baclofen over AA because of this and he recommends AA to everyone.  My wife had been on baclofen for nine months before seeing him so was able to present herself sober but we only went to see him to get our GP to increase dosage from 80.

In that sense, the success of baclofen worked against us. Chick would only go up to 100 mg a day and lined my wife up with another patient to take her to an AA meeting.  My wife had been through AA 50 meetings regime and residential rehab at Clouds House.  Like Ameisen, it didn't work.  

This then cause another problem. The GP reluctantly went up to 100 mg but that was it and it was not enough.  

I then went and got myself a prescription from a different GP on the basis that I had restless leg syndrome, which was true, and got an additional 30mg a day but this still was not enough, so I thought.

As I had no idea how to administer the drug I assumed it should be taken in three daily doses and I calculated the dose based on body weight to get 270mg a day.  I then insisted my wife take 90mg at a time and she refused because of the side effects.  That is when I found Heydtmann who explained how to spread the dosage evenly and he prescribed over 100mg.  But, that was a year and a half into the treatment regime for my wife and I was working full time, desperate to hang on to my job so I took time off work to oversee the new dosage.  By using an hourly schedule of small doses, the litre a day habit stopped dead in its tracks.  That was like a miracle.  The problem then was that my wife went into severe DTs after three days of being dry and that led to our legal problems when I called out our GP who decided to send my wife to a big inner city hospital where they did not use baclofen and they deal with alcoholics by having them arrested and taken to the police station.  I realized this as the ambulance drove off but my ever so clever GP assures me that this was ok rather than sending her to our local hospital where Dr Heydtmann worked.  I actually ran down the road after the ambulance.  My next phone call was from the police and then my wife was in my court and I was being disciplined by my employer, had social services trying to take me to court and eventually I lost my job because I was ill from stress.

Perhaps this is why I have had people say I am a zealot and they don't see where I am coming from. If you have seen an alcoholic drinking like my wife does, for years, and utterly destroying her life and yours, and baclofen just makes them reach for a glass of water, you realize how radical and extraordinary this drug is.  I can also see why, if a lot of occasional heavy drinkers are taking baclofen, that the side effects would pose a problem because of their jobs

Does that make sense?

 

Edited by Otter

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Molly78

Ameisen describes "a routine of debilitating binges punctuated by gruelling abstinence".  He also says "I never set foot in my office or the hospital when i was not completely sober".  So I don't think he could have been drinking continuously all day.  He notes that the danger period was late afternoon - as for so many of us who exist for a while as "functioning alcoholics".  I never saw him as someone who drank a litre of vodka every day while trying to work as a doctor.

I think we have got back into the old circular argument of who is or isn't "a proper alcoholic".  This discussion has caused unrest in the past, I think we should drop it.

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Otter

Yes, but in the end, he stopped practicing and that is when he started taking baclofen.  I didnt' read the book as saying he was abstaining after he left his practice.  I don't remember what his level of drinking was but one story he told was of trying to kid his doorman that he wasn't an alcoholic by wearing his Legion of Honour award.

The issue  of "who is and who is not an alcoholic" is a false argument.   The diagnosis of alcoholism is not based on scientific or medical tests.  It's based on social consequences to the sufferer and is largely arrived at by self-description. 

In my paper, I raise this issue because I try to make the point that alcoholic addiction arises from a neurologcial anxiety condition.  I would think that some people have this to a greater degree than others. It is progressive.  Everyone is different.  

My attitude is more:  No one is an "alcoholic" because the term doesn't clearly identify an illness, only negative social consequences.  If one were able to administer tests, such as liver tests, brain scants blood tests, and one could ascertain in each case exactly what the cause of the illness was, then one could give it a name, and it might be of a different origin in different cases.  Some people may have a genetic disposition to it, in that they have a low level of a particular brain chemical,  GHB, for instance. Some people may have low serotonin levels.  Some people may have brought their condition about by drinking alcohol, and stopping alone may restore their health.

 

I don't have any real idea about this issue and how one would go about testing for it.  There is a blood test which can be administered to determine if alcohol is still in the blood but I don't know much about it. The French team talk about it as a way of determining whether trial participants are telling the truth about whether they have stopped drinking.

When I met my wife she drank heavily over a period of a few days and would then stop abruptly.   She would have a few weeks of sobriety and then binge again.  It was a monthly event so I put it down to hormones. She stopped drinking when she fell pregnant and for several months afterward.  However, once the health visitor stopped coming to the house after our son was about six months old, she began drinking and the old pattern returned.    Then, for various reasons, she got into trouble with being seen with our son while appearing under the influence.  My office was across the street from the Social Services offices...

After they became involved initially and insisted we put our son into day care, that left my wife alone at home all day and she just started drinking every day.  I think that is what probably happens to a lot of people, that they go down the pan when they lose their jobs so there's no point going through painful abstinence.  I got the impression that, in the end, he gave into it completely.

In my paper I deal with this issue by suggesting DSM V be used to assess whether someone is suffering from an "illness".  It also relies on "negative outcomes" but since it is an accepted standard, it is a useful tool in determining how serious the illness is.  

My point about the Dutch study is that they selected people who had been in rehab.  My experience with residential rehab programs is that they insist that patients are abstinent when they start the program and most go for about 12 weeks.  This means the Dutch study not only selected people who were sober for some time, and had had psycho-social counselling, but these were people who were able to achieve sobriety on their own, prior to the rehab.  My wife was in that category when she went to Clouds but that was over 20 years ago and at the time she also held down a job and had worked all her life.  

Why I don't like the Dutch study is that it uses this measure to say that baclofen may not be effective for alcoholics.  First, they have accepted a definition of alcoholism based on self-description so we don't know what the physical cause of these people's addiction was.  Secondly, these must have been relatively low level alcoholics, because they were able to abstain prior to rehab, during rehab and were also able to self-administer baclofen during the trial.  

 

Here's the contradiction.  Having found this group of participants and seeing that they did no better than those on placebo they were then able to say for ALL alcoholics, that baclofen showed no promise.  However, in my wife's case, she could not, when she started baclofen, stop drinking at all, until she became so ill that she threw up for two or three days.  She could not stay sober to attend rehab, in fact she was kicked out of a subsequent course of counselling because she turned up drunk, and she was drinking a litre of alcohol a day so could not self adminster baclofen.  Yet, for this "alcoholic" the treatment worked by stopping the addiction dead in its tracks.  When I administered higher levels of baclofen through the day under supervision of Dr. Heydtmann, I would put a glass off water next to her vodka and she would reach for the water.  This is the point I am getting at.  If one drinks to excess only irregularly, and not a litre a day, one may reach the switch and realize one day that there is no craving, that one is at a restaurant and doesn't want a drink.  But, if you are drinking a litre a day, you will, with a high enough dose, just stop drinking completely and have no desire to drink alcohol, in the middle of a lengthy binge. 

 

My issue is that it is this type of "sufferer" who is most at risk from alcoholism.  In my discussions with Dr. Heydtmann and my visits to his ward, I realized that there were much worse cases than my wife.  She had many liver tests and luckily they were ok.  Many other patients of Dr. H drank more than a litre a day and my wife's habit was not out of the ordinary and, indeed, less severe.  I was amazed at how much severe alcoholics do drink. But, none of this type of alcoholic ever gets into the trials because they cannot self administer.  My wife's case is unusual because she only succeeded because I administered the baclofen and I did that daily for years.  When she was sober, I would hand her the pills at the right times and when she relapsed, I would put them in her mouth and pour water into her mouth.  It was that bad. 

It does cloud the issue to get into some kind of debate about who is and who is not an alcoholic. It's not like there are points awarded.  I'm not trying to one up anyone. What concerns me is that these trials don't pick participants out in a way that will show that baclofen works very well for alcoholics who are most dangerously addicted and in end stage alcoholism.  Dr. Heydtmann's patients are mainly cirrhosis patients.  These kind of results could deter doctors from using it for serious cases, because low level alcoholics didn't do better than placebo.  That may be because they didn't need it, or, since they were abstinent at the commencement of the trial, they found the side effects were off-putting.

 

 

 

 

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