If baclofen is so great, why isn’t everyone using it already?

It should be pretty simple.

Alcoholism is a huge health and social problem in many countries in the world.

There are an estimated 270,000 alcohol dependent people in Australia. Every day in Australia, 15 people die and 430 are hospitalised for alcohol related illness.

Some alcoholics respond to simple interventions. Others try but fail the current treatments on offer. For most, alcoholism is a chronic relapsing condition at best and at worst, a fast track to poor health and social disintegration.

If you’ve reviewed the section How baclofen is different from other alcohol addiction treatments, you’ll know already that the current alcoholism treatments are pretty ineffective and that there have been no really new or innovative advances in the treatment of alcohol addiction for decades now.

So what if a new treatment came along? If there were studies showing it to be much more effective than currently used treatments and lots of reports from patients describing how it worked where all else had failed.  As a bonus this was not a new and untested medication but an old cheap one which had been used for decades so we knew a lot about it over short and long term use. This old medication was being proposed for a new use, in alcoholism with its devastating health consequences and largely ineffective treatments. This would put the risk:benefit ratio greatly in favour of giving it a go. It wasn’t going to work in everyone but it looked like it could help 50% or more of people who had failed all other treatments. Worth a try at least.

So why isn’t everyone who looks after alcoholic patients prescribing it?

When I searched through the information about baclofen for alcohol addiction treatment, I wondered what the problem was. As I read further about the French experience with baclofen and discussed baclofen with medical colleagues who treated various aspects of alcoholism in Perth, I started to see why this was not going to be a smooth road.

Baclofen turns basic ideas about the treatment of alcoholism on their head.

There were some new and radical concepts emerging:

  1. Maybe it’s not that alcoholism is really hard to treat, rather that we didn’t have effective enough treatment for it.
  2. Maybe alcoholism isn’t inevitably a chronic, relapsing disease with a poor prognosis. Maybe if we treated alcohol dependence earlier with more effective treatments, we would see a radical change in the natural history.

That’s the root of the problem. It’s a new paradigm and in a fundamentally conservative profession like medicine, new ideas often take a long time from invention to adoption, around 10-15 years on average. This is not all bad. The first principal of medicine is “first do no harm”. But can also create long delays in important new treatments becoming widely available.

When I delved into the story of baclofen in France, it was obvious that there were two radically different opinions about baclofen for alcoholism treatment.

On one side were the Baclofen Supporters who felt that the slow acceptance of baclofen as a safe and valid treatment for alcoholism was criminal because of the health and social carnage caused by alcoholism in France. They cited the 130 deaths per day from alcoholism which continued while French health authorities argued that baclofen was not safe enough and that there was not enough scientific evidence to support it’s use.

The Baclofen Sceptics deplored the unconventional way in which baclofen treatment for alcoholism had become known. An alcoholic doctor experimenting on himself then publishing his anecdotal experience in a book designed for the general public.

What was interesting about the Baclofen Sceptics was that they didn’t contest the efficacy of baclofen – this had been shown in clinical trials, albeit few in number. Their argument was not that baclofen didn’t work but rather that it was too dangerous to be used for the treatment of alcoholism. This didn’t really make sense to me. Baclofen hadn’t been considered a dangerous medication while being used during four decades to relieve muscle spasms. Remember that baclofen wasn’t TREATING the cause of the muscle spasm, the spinal injury or multiple sclerosis, it was simply providing symptom relief and comfort.

Using baclofen for alcoholism was a very different proposition: it was being used to treat a condition which caused serious health problems and premature death and where current treatments failed most patients. So the argument of the Baclofen Sceptics that baclofen was too dangerous for use in alcoholism seemed nonsensical to me. Logically we should be accepting more, not less, risk for alcoholism treatment.

The Baclofen Sceptics also emphasised the side effects of baclofen, especially at the higher doses required to achieve suppression of cravings in some patients. That baclofen had side effects had never been disputed by baclofen supporters- the side effects can be very unpleasant but they generally disappear with time and are always reversible with reducing or stopping baclofen. It seemed to me though that alcoholism has such devastating effects on the health and lives of patients, that the focus should be on helping patients manage baclofen’s side effects so they could get the therapeutic effects. And in the end, it’s actually patients who decide to continue or cease baclofen treatment in the face of side effects

Other main argument of Baclofen Sceptics centred around their strongly held belief that the only possible aim of alcohol addiction treatment was permanent and total abstinence. They were appalled at the claim of baclofen prescribers that alcoholic patients on baclofen could aim for safe levels of drinking rather than abstinence if they wished. This was seen as totally irresponsible and impossible to achieve (link). This attitude didn’t make sense to me. If baclofen treatment could extinguish cravings for alcohol, then patients could potentially drink alcohol in a normal pattern ie in an occasional fashion or at safe levels. I couldn’t see how baclofen’s ability to allow safe levels of drinking made it dangerous to use.

As much as I searched and researched the arguments of the baclofen sceptics, I simply couldn’t find any which passed the credibility test for me.

It was also very instructive to look at how other radical new treatments had fared in the early years after their discovery. Baclofen is not the only treatment to have had a slow and difficult birth.

There was much to be learned from the experience of Nobel Prize winners, Dr Barry Marshall and Robin Warren and the story of their discovery of the role of the bacteria H. pylori in causing stomach ulcers and stomach cancer. They were both working at my institution, the Royal Perth Hospital, when they made their initial discoveries.

It’s well known that they had struggled for years to have their radical idea accepted: that a bacteria found in the stomach was the direct cause of stomach ulcers. This new idea challenged the accepted wisdom that stomach ulcers were caused by psychological stress leading the stomach to produce excessive acid which ulcerated the stomach lining.

We know that eventually the idea that H pylori caused stomach ulcers and cancer was accepted and radically changed the treatment of this common condition. But it took well over 10 years.

This extract of an article from Barry Marshall makes instructive reading: (Link)

Interviewer: How did you get the word out about your discovery?

Barry Marshall: I presented that work at the annual meeting of the Royal Australasian College of Physicians in Perth. That was my first experience of people being totally skeptical. To gastroenterologists, the concept of a germ causing ulcers was like saying that the Earth is flat. After that I realized my paper was going to have difficulty being accepted. You think, “It’s science; it’s got to be accepted.” But it’s not an absolute given. The idea was too weird.

Then you and Robin Warren wrote letters to The Lancet.

Robin’s letter described the bacteria and the fact that they were quite common in people. My letter described the history of these bacteria over the past 100 years. We both knew that we were standing at the edge of a fantastic discovery. At the bottom of my letter I said the bacteria were candidates for the cause of ulcers and stomach cancer.

That letter must have provoked an uproar.

It didn’t. In fact, our letters were so weird that they almost didn’t get published. By then I was working at a hospital in Fremantle, biopsying every patient who came through the door. I was getting all these patients and couldn’t keep tabs on them, so I tapped all the drug companies to request research funding for a computer. They all wrote back saying how difficult times were and they didn’t have any research money. But they were making a billion dollars a year for the antacid drug Zantac and another billion for Tagamet. You could make a patient feel better by removing the acid. Treated, most patients didn’t die from their ulcer and didn’t need surgery, so it was worth $100 a month per patient, a hell of a lot of money in those days. In America in the 1980s, 2 to 4 percent of the population had Tagamet tablets in their pocket. There was no incentive to find a cure.

You published a synthesis of this work in The Medical Journal of Australia in 1985. Then did people change their thinking?

No, it sat there as a hypothesis for another 10 years. Some patients heard about it, but gastroenterologists still would not treat them with antibiotics. Instead, they would focus on the possible complications of antibiotics. By 1985 I could cure just about everybody, and patients were coming to me in secret—for instance, airline pilots who didn’t want to let anyone know that they had an ulcer.

I found it unbelievable that gastroenterologists would refuse to give ANTIBIOTICS. Treatment of a medical condition with antibiotics is not exactly radical so I did doubt this. Until I found this 2004 discussion of the Marshall:Warren story. Here is the relevant paragraph with the link below.

As mentioned, there were already highly effective treatments for PUD by the early 1980s. The rate of complete healing of endoscopy-proven duodenal ulcers, after several weeks of treatment with potent inhibitors of acid production, is about 95 percent (Straus 1996). Symptomatic relief occurs within a couple of weeks (McFarland et al. 1990). Such treatment, moreover, is remarkably safe and free of side effects. The same cannot be said for metronidazole, the first widely used antibiotic for H. pylori. This and other proposed antibiotic treatments for H. pylori have unquestioned side effects, some of which mimic the symptoms of the very disease for which they are prescribed. These can pose significant disincentives for patients who would like to feel better.

Read Bacteria, Ulcers, and Ostracism? H. Pylori and the Making of a Myth.

There are a lot of parallels between the unfolding of the H pylori/antibiotic and baclofen stories:

  • a simple, effective but revolutionary treatment is discovered by individuals who are not decision or opinion makers in this area.
  • these individuals see the potential to help many patients with a common and debilitating health issue.
  • the cause of the problem has been blamed on the patient – stress for peptic ulcers and lack of willpower/motivation in the case of alcoholism.
  • the new treatment paradigm is met with scepticism by the profession who logically should embrace it in the interests of their patients.
  • the response is ridicule, hostility or disinterest.
  • the “new” treatment is not a new/novel medication. It’s well known and safe having been used for decades in patients for other indications.
  • while the profession does not believe that the new treatment works for this indication, they also don’t undertake or facilitate the research to prove this.
  • the profession actively dissuades patients from having the new treatment by citing the complications of the treatment.
  • the new treatment has no profit potential because it is out of patent.
  • there is an active conflict of interest from pharmaceutical companies who are making money from the established treatments, even though they are inferior to the new treatment.
  • patients were more willing to try the treatment than doctors were to prescribe it.

Baclofen is not as radical a change in treatment as Marshall and Warren’s discovery of H pylori but looking at their story goes a long way to explaining why baclofen’s adoption as a treatment for alcoholism has been so slow.

When Olivier Ameisen published a case report of his self treatment with baclofen in 2005 in Alcohol and Alcoholism Papers, he was convinced that baclofen treatment would be rapidly adopted and would revolutionise the treatment alcoholism of alcoholism in a few short years. When this didn’t happen, he published his book “The End of My Addiction” in 2008 in which he not only described his experience but also that of clinical trials already done and reports of patients who had used baclofen to get benefit. The book sparked a lot of interest amongst alcoholics and their families who clamoured to get baclofen treatment. The problem at that time was finding a doctor in France who was prepared to prescribe it. Ameisen’s book cited only one prescriber in France, Dr Renaud de Beaurepaire, but soon a few other “early adopters” started to prescribe. This number has increased steadily and there is now a network of around 10,000 prescribers in France. They are predominantly GPs who, after listening to the arguments for and against baclofen treatment, were prepared to prescribe it “off label” for their alcoholic patients and judge the results for themselves. In France the number of patients treated with baclofen for alcoholism has seen an exponential growth since 2008 with current numbers exceeding 100,000 patients.

The rapid rise in uptake baclofen use for alcoholism has been because of “people power” – the relentless pressure from patients to be prescribed baclofen because they have learnt about it from popular media, blogs and patient association websites. This is a new phenomenon, very much of our age. It’s a type of Trip Advisor for treatments – patient experiences en masse being available for everyone to see and the “good, bad and ugly” are all exposed.

As with the H. pylori story, the baclofen story involves clashing with the interests of pharmaceutical companies. They are businesses and their job is to sell their medications to make a profit. Their bottom line is not about helping patients get the BEST treatment, just THEIR treatment.

This has two effects on innovative treatments, especially those which are out of patent:

  1. There is a tangled relationship between the pharmaceutical companies and established, influential clinicians and their professional bodies. The pharmaceutical companies provide easy, abundant money to do research and advance the field but only in the interests of their products. The clinicians can find itself in a difficult place because there are often precious few non-industry sources of money for clinical research. When a newly developed medication is either not as effective as alternatives or frankly dangerous, there is a serious conflict of interest between the interests of patients and of the pharmaceutical company. The pharma industry will go to great lengths to keep their product outselling others. They use specialist opinion makers to give their products credibility, they suppress unfavourable data both pre and post release of the medication, often with the complicity of clinicians who have serious conflicts of interest and do not speak up. Many examples of this have been revealed over the years such as the Vioxx story. http://www.nytimes.com/2004/11/14/business/despite-warnings-drug-giant-took-long-path-to-vioxx-recall.html?_r=1
  2. When an old, out of patent medication becomes the most effective treatment for a common medical condition, it creates a big problem for pharmaceutical companies because they stand to lose a lot of money. But that’s only the start of the problem which baclofen’s wider use would create for them. Remember that the current treatments only improve outcome by 10% over placebo. That sets the bar pretty low. Even a small improvement on this, say to 20% over placebo would be a big advance in a massively costly condition like alcoholism so developing a slightly more effective medication would be highly lucrative. But baclofen raises the bar a lot- improving outcome by 40-50% over placebo for a very modest price. It’s going to be hard to top that. The BACLAD study demonstrates the problem. Treatment with placebo resulted in 3 month abstinence rates of 24% of placebo treated patients and 68% in the baclofen treated group. Finding a novel medication which works better than baclofen will be difficult. It’s more likely that new developments in alcoholism treatment medications will seek to simply modify baclofen itself to improve characteristics such as the half life or side effect profile rather than looking for novel molecules, at least in the near future.

Any work which develops more effective or convenient baclofen variants or new medications is to be strongly encouraged because addiction medicine is in dire need of more effective treatments.

So my answer to the question “If baclofen is so great, why isn’t everyone using it already?” is that it’s not a problem with baclofen itself but about the various interests which have played out around it.

What convinced me to use baclofen and promote baclofen use for alcohol addiction was this combination of factors:

  1. Alcoholism has devastating health and social consequences.
  2. A lot of patients try and fail all the current treatments.
  3. The current treatments actually aren’t very effective.
  4. Baclofen is an old medication considered safe for over 40 years.
  5. Baclofen works better than current treatments.
  6. Baclofen sceptics don’t have any convincing arguments against using it.