Monday, August 10, 2009

Ameisen's Miracle Molecule

Applauded by many for his personal courage and slated by some for his controversial claims, Dr Olivier Ameisen bared his darkest secret to the world in his recently published memoirs and triggered an impassioned debate over his claim to have discovered a cure for alcoholism.

The Paris-born cardiologist had a brilliant career at one of America’s top teaching hospitals when he developed a profound addiction to alcohol. His binges would last several days until the damage he inflicted on his body would compel him to admit himself to hospital with serious, and at times, life-threatening injuries.

He broke bones with no memory of falling; he nearly lost his kidneys; he almost died from massive seizures during acute withdrawal. For him, “alcoholism was a biological prison and there was no way to break down the walls”.

When Olivier feared his addiction could put his patients at risk, he abandoned his flourishing practice in New York City, and then, fearing for his own life, immersed himself for three years in Alcoholics Anonymous, various therapies, rehab – eight times – and a plethora of medications. Nothing worked.

During this struggle, he repeatedly complained to his doctors that if they could treat his chronic anxiety disorder, his alcoholism would be cured. Then he happened upon an article in the New York Times in 2000 about a researcher studying the effect of a muscle relaxant called baclofen on a drug addict’s addiction to cocaine.

Baclofen has been used safely for years as a treatment for various types of muscle spasticity, but has more recently shown promising results in studies with laboratory animals addicted to a wide variety of substances.

Olivier self-prescribed the drug and experimented with increasingly higher doses until he finally reached a level high enough to leave him free of any craving for alcohol. That was more than five years ago.

"After years of battling uncontrollable addiction, I have achieved the supposedly impossible: complete freedom from craving," he says with a forthright sincerity that is characteristic of his writing in his book “The End of My Addiction”.

Olivier theorises that baclofen relaxed his chronic muscular and nervous tension, kept it from intensifying into chronic anxiety and panic, and thereby short-circuited the craving for alcohol to resolve that extreme distress.

The results for him were truly remarkable, and his self-case report published by the journal Alcohol and Alcoholism in 2005 gathered slow but intensive interest.

His findings presented a new concept: medication-induced complete and prolonged suppression of substance-dependence symptoms with alleviation of co-morbid anxiety.

But this thesis was largely met with resistance from the some members of the medical community - though his work was later supported by the findings of other researchers - and in response, he says, he wrote this book.

‘The End of My Addiction’ (Piatkus 2009) is both an autobiography and a groundbreaking call to action – “an urgent plea for research that can rescue millions from the scourge of addiction and spare their loved ones the collateral damage of the disease”.

When it was first published in France in late 2008, it became an instant bestseller. With its eye-catching message, ‘Le Dernier Verre’ (‘The Last Glass’) prompted thousands of recovering alcoholics to ask their doctors for baclofen. The English translation, which was published in March this year, sparked a predictable worldwide escalation of interest in this cheap and once inconspicuous drug.

In sharing the story of this discovery and his recovery, and with unsparing honesty, Olivier also bravely recounts every explicit and painful detail of his fall from grace, from reason, and from the lofty heights of a specialist medical practice among America’s elite.

Born and raised in Paris, Olivier says he was a lifelong sufferer from chronic anxiety and panic attacks. The son of Holocaust survivors, he was a prodigiously gifted pianist, but opted ultimately for a career in medicine, which he thought would give him the security he craved. In 1983 the young doctor moved to New York to join the prestigious cardiology team at New York Hospital and Cornell University Medical College (now New York-Presbyterian Hospital and Weill Cornell Medical College), where he became respectively an associate attending physician and associate professor of clinical medicine. In addition, he opened a successful private cardiology practice in Manhattan in 1994.

As an active participant in cardiology research at New York Hospital/Cornell, Olivier co-authored 16 papers in peer-reviewed medical journals on the evaluation of coronary artery disease and related topics.

Yet, he was still plagued by feelings of self-doubt and imminent failure. “Throughout my life I had been plagued by anxious feelings of inadequacy, of being an impostor on the brink of being unmasked constant anxiety,” Olivier writes.

He was unable to quell the anxiety he constantly felt until, in his 30s, he turned to alcohol as a form of self-medication. He recalls: “I hated the taste. I would drink whisky and hold my nose as I drank.” And from a social drinker, he became a hopeless alcoholic.

“As my drinking had increased, I had scrupulously honoured my first duty as a doctor - to do no harm. I stopped driving. And I never set foot in my office or the hospital when I was not completely sober.

“But the fact is, I was terrified of living without alcohol. Without it, I would be an anxious wreck. Despite the outward successes - at the very nadir of my alcoholism I was awarded the French Legion of Honour for services to medicine - I struggled with a deep sense of failure, and feared that the world would see that my accomplishments were nothing but a sham,” he confesses.

Occasionally, in a veiled appeal for help, Olivier would discreetly ask his medical colleagues about how to help ‘someone’ with a drinking problem. They’d ask, “Is the person close to you?” If he said no, they’d say, “You don’t want to get involved, it’s a minefield.” If yes, “Well I really don’t know what to say. It’s very complex…”

Recent studies have shown that, at least among doctors who are not specialists in the field, missed or delayed diagnosis is the rule, rather than the exception, in cases of addiction. One study videotaped doctors and patients and found that when patients mentioned addiction issues, doctors tend to change the subject as quickly as possible.

“I didn’t know what to make of this phenomenon when I first encountered it. But it dawned on me that doctors are uncomfortable with the subject because they don’t have a reliable treatment to deliver or recommend,” Olivier suggests.

The lack of a reliable treatment also explains the moral assumptions attached to addiction, he continues. “Admitting my problem drinking to most of my friends and my colleagues terrified me, too. I feared being ostracised, and since I felt that drinking should be under my control I felt ostracism would be justified.”

Naively, he assumed that very few doctors had a drinking problem, when in fact research has shown that ten percent of doctors will become dependent on alcohol at some point in their lives. And, according to the British Medical Association, doctors are three times more likely than the general population to have liver cirrhosis from alcohol abuse.

Between binges, Olivier clung to abstinence, called his AA sponsor regularly, visited his therapist and worked overtime in his practice so that he had no free time for drinking. But inevitably the cravings would consume him again and he would drink for days.

“Through my drinking I broke my shoulder, my wrist and three ribs. I often considered taking my own life. I had a feeling that I could easily have a bad accident that would result in me breaking my back and living the rest of my life as a paraplegic. But something held me back. It was this feeling that if I died, I was sure that someone would discover the cure for this disease the day after.”

As his need for alcohol increased, he began to ease himself out of his practice. He told all his doctors: “I use alcohol as a tranquilliser. If you rid me of anxiety, I'll stop drinking.” His doctors all told him: “You're anxious because you drink. Stop drinking and your anxiety will subside.”

Olivier’s suspicion was that his chronic physical uneasiness was triggering addictive behaviour, which was then exacerbated by this self-medication gone wrong.

He began to have paralysing panic attacks. These began innocuously enough with a twitching in his calf muscles. The next symptoms were tightness in his chest; he felt he couldn't breathe. And then unstoppable panic took over his whole being.

“I began increasing my intake of the drug that brought relief: alcohol. Talk about a slippery slope. The more I drank to ease my anxiety, stave off panic and counter insomnia, the more I had to drink for the same effect.

“I was an accident waiting to happen. When, in August 1997, I wound up in New York Hospital with acute withdrawal seizures that nearly killed me, it was devastating - and a great relief. I thought: 'I am no longer hiding my drinking from anyone. Now I will get proper treatment and recover’,” he admits.

Fearing for his own patients, he gave up his practice and returned to Paris. Over the next three years Olivier tried everything from rehab to prescriptions for tranquillisers and anti-depressants. He also tried acupuncture and hypnotherapy, both of which had zero effect. He consulted a highly recommended specialist in cognitive behavioural therapy to try to resolve the emotional experiences that triggered drinking, but this therapist seemed more interested in turning Olivier from a binge spirits drinker into a moderate wine drinker.

“I told every doctor and therapist I saw that my fundamental problem was anxiety. None took this seriously.”

One day in November 2000, a former girlfriend sent him an article she came across in the New York Times about a researcher studying the effect of a muscle relaxant called baclofen on a drug addict's craving for cocaine.

“I read with fascination about how scans conducted by the psychologist Dr Anna Rose Childress, an addiction researcher at the University of Pennsylvania, showed a remarkable quieting of brain activity in a cocaine addict who was taking baclofen to control spasms. The addict said this medication reduced his craving substantially.

“I did not want to get my hopes up too much, but I did wonder: Could baclofen help me stop drinking?”

Over the next couple of months, he started taking baclofen, steadily increasing his dose to 180 milligrams a day. The short-term results were remarkable. It relaxed his muscles completely and gave him a peaceful sleep - both things he had never experienced before.

“It reduced my craving for alcohol and enabled me to remain abstinent for longer periods between binges. But I still had binges - and with them came the blackouts and accidents.

“In order to reach a point where I would lose the motivation to consume alcohol at all, it seemed I'd have to increase the baclofen dose. But I was in unknown territory, already taking six times the dose used in previous brief experiments with alcoholics.”

But in January 2004, he decided it was now or never: if he continued to follow his doctors' advice, he felt he would keep lapsing into binges and eventually die from drinking. He had to take my treatment into his own hands.

Based on animal studies, he decided that by increasing the dose gradually he could tolerate up to 300 mg. At 270 milligrams he went out with friends for tea. “I saw a man to my right drinking whisky - and I felt neutral. I looked at him again. Again I felt neutral. Since the onset of my alcoholism, this had never happened - I'd have wanted a drink, too. Within five weeks of taking the higher does, baclofen had made this change in me happen. I dared to look at the bar with its gleaming bottles. No alcohol thoughts came to mind; no craving for alcohol troubled me. I thought: 'I am in a fairy tale or a dream. In a moment the spell will break, and I will wake up to the horror of needing a drink.' But I didn't,” he says.

Olivier gradually reduced his intake of baclofen over the next two weeks to 120mg; it appears that going up to 270 mg had apparently triggered a threshold response, which could now be maintained at the lower dosage.

Five years later, Olivier is still taking Baclofen, and he remains free from cravings and liberated from the curse of alcoholism that had plagued him for almost two decades.

“By completely suppressing my addiction, baclofen saved my life. I believe it can save and improve the lives of many others by completely suppressing their addictions, and I have written his book to that end”.

Olivier currently is Visiting Professor of Medicine at State University of New York Downstate Medical Centre, and divides his time between New York and Paris.

What his colleagues say:

Some doctors have decided to overlook the fact that baclofen is not authorised for treating alcoholism, and are reporting exciting results.

"I prescribed it to two alcoholics who were really at the end of the road. To be honest, it was pretty miraculous," says Dr Renaud de Beaurepaire of the Paul-Guiraud hospital at Villejuif near Paris. "Ameisen has made an extraordinary discovery," he adds. "The whole world will thank him for it."

Dr Pascal Garche of the Geneva University Hospital alcoholism unit has also conducted a limited experiment. He gave 12 patients a course of baclofen. Seven showed remarkable signs of recovery. "I have never had reactions like this before," he comments. "We cannot ignore findings such as this - The book is going to set the cat among the pigeons." Dr Garche admits that some patients withstand large doses of baclofen better than others. He has sought permission to extend his programme.

Other medical specialists are sceptical and even angry that Dr Olivier Ameisen should claim there is a simple pharmaceutical solution to what they insist is a complex physical, mental and social disease.

"Encouraging people to think that there is a miracle molecule is to completely misunderstand the nature of alcoholism, and is extremely irresponsible," says Dr Michel Reynaud of Paul-Brousse hospital in Paris.

"We need comprehensive tests to determine how this drug acts, if it is effective and at what dosage, and if it is genuinely harmless in the longer term," says Alain Rigaud, President of France’s National Association for the Prevention of Alcoholism and Addiction. "But even if it turns out to work, that does not mean a drug alone is the solution."

Since the publication of Olivier’s book, a spokesperson for the French government agency, which tests and approves drugs, L'Agence française de securité sanitaire des produits de santé (Afssaps), has cautioned that baclofen is "not an anodyne drug" and can have adverse side effects. However, he said the agency is considering "how to organise clinical trials" which would put Dr Ameisen's claims to the test.

It has been remarked in the media that no pharmaceutical company would sponsor such trials because baclofen has been out of copyright since 1997.

Dr Olivier Ameisen issues a heart-felt appeal to medical colleagues in his book: “Until a randomised clinical trial of dose-dependent baclofen is mounted, I ask all doctors who treat addiction to consider prescribing baclofen off-label for case of those patients who remain ill despite exhausting therapies and have no alternative treatment for a devastating and often deadly disease.”

He also calls on Government health agencies and officials, politicians, non-governmental health organisations, and citizens to support full-scale randomised clinical trials of high-dose baclofen.

How does it work?

Exactly how baclofen produces craving suppression and alleviates underlying dysphoria must still be explained by further research. But important parts of the answer have been established. Baclofen affects the neurotransmitters dopamine, GABA, and glutamate. It enhances GABA activity, reduces glutamate, and through these effects reduces dopamine. In so doing it seems to play a role in balancing the brain’s reward mechanism.

In addition to the fact the baclofen has been shown to does-dependently suppress motivation to consume alcohol, cocaine, heroin, nicotine, and amphetamine in animals, low-dose baclofen has been shown in randomised trials with dependent patients to reduce craving for cocaine and opiates as well as alcohol, and in an open trial, craving for food binge eating and bulimia.

While Dr Olivier Ameisen has reported no side effects after five years of using baclofen, hallucinations and seizures have occurred from abrupt withdrawal of Baclofen. Side effects have included: somnolence, dizziness, paresthesia, nausea, vomiting, headache and constipation. There is a report of a Baclofen overdose (300 mg with alcohol), which led to severe respiratory depression requiring airway and respiratory support.

A 2007 study published in the Lancet concluded that baclofen is effective at promoting alcohol abstinence in alcohol-dependent patients with liver cirrhosis, and could have an important role in treatment of these individuals.

Dr Giovanni Addolorato, Institute of Internal Medicine, Catholic University of Rome, Italy, and colleagues did a trial of 148 alcohol-dependent patients with liver cirrhosis that had been referred to their institute.

The researchers found that 71 percent of the baclofen patients (30/42) achieved and maintained alcohol abstinence, compared to 29 percent (12/42) of those receiving placebo. Patients taking baclofen also abstained from alcohol for more than twice as long as patients given placebo (62.8 days versus 30.8 days).

Alcoholism –

Worldwide, about ten percent of the population is vulnerable to becoming dependent on alcohol, and significant percentages are vulnerable to developing dependence.

A report published by the Health Research Board (HRB) in 2007 shows that alcohol consumption in the Irish population has increased by 17 percent over the past 11 years, from 11.5 litres per adult in 1995 to 13.4 litres in 2006.

This rise in consumption has led to increases in alcohol-related harm and disease, and has resulted in more than 1,775 deaths.

According to an EU survey on alcohol consumption published in 2007, Ireland topped the poll, with 34 percent of Irish people questioned saying they "usually" binge drink,