Sylvie Imbert1, Samuel Blaise2, Jacques Bérard3, Renaud de Beaurepaire4*, Amanda Stafford5 and Philippe Jaury6
127 rue Louis Blériot, 31380 Plaisance, France
Received: 18 September, 2017; Accepted: 23 October, 2017; Published: 24 October, 2017
Renaud de Beaurepaire, GHPG, 54 avenue de la République, 94806 Villejuif – France, Tel: 33142117088, Fax: 33142117089; E-mail:
Imbert S, Blaise S, Bérard J, de Beaurepaire R, Stafford A, et al. (2017) A prescription guide for baclofen in Alcohol Use Disorder- For use by physicians and patients. J Addict Med Ther Sci 3(4): 032-041. DOI: 10.17352/2455-3484.000024
© 2017 Imbert S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Expert patients; Indifference; Individual adjustment; Adverse effects; Therapeutic alliance; Alcohol disorders; Baclofen
Since the discovery by Olivier Ameisen that high-dose baclofen can produce a state of indifference towards alcohol in those with Alcohol Use Disorders (AUD), the prescription of baclofen in AUD patients has exponentially increased. There are currently hundreds of thousands of patients with AUD who benefit from this treatment in France. However, the prescription of baclofen is difficult in many ways. First, the treatment, which consists in a slow progressive increase of doses, must be individually adapted, some patients needing low doses to achieve a state of indifference, while others need high or very high doses. Second, baclofen produces many adverse effects that can be very uncomfortable for patients, and may sometimes be dangerous. The third is that the patients must be strongly engaged in the management of the treatment, as they are the ones who will have to find the best way to target the moments of cravings and determine the distribution of the doses over the day to limit the occurrence of adverse effects. The doctor: patient therapeutic alliance is therefore a crucial element in the management of baclofen treatment. The present article is a guide written by both doctors and cured patients (“expert patients”) for the prescription of baclofen in AUD.
The Hypothesis of Professor Olivier Ameisen
Olivier Ameisen was a brilliant cardiologist suffering from an Alcohol Use Disorder (AUD), refractory to all alcohol dependence treatments. For him, alcohol dependence was a neurological disease: the symptoms of cravings and loss over control over drinking were due to abnormalities in brain functioning. Treating alcohol cravings with medication targeting the brain networks involved would treat the disease of alcohol dependence.
The conventional treatments for alcohol dependence could diminish but not eradicate cravings. When Ameisen looked at animal models of alcohol dependence, he found that baclofen was the only pharmaceutical agent capable of completely extinguishing cravings for alcohol. The effect of baclofen on cravings increases with increasing doses and the extinction of cravings happens at doses of around 3mg/kg. Amiesen hypothesized that the effect in rats might also happen in humans so he treated himself with similar doses of baclofen. At a dose of 270mg/day, Ameisen became “indifferent” to alcohol.
After having published a case report of his own experience in 2005 , Ameisen proceeded to publish a book about baclofen treatment for AUD “The End of My Addiction” , first in France in 2008 then worldwide.
The Concept of Indifference
The aim of baclofen treatment is to render the patient “indifferent” to alcohol. Baclofen is the only current AUD treatment capable of producing this effect.
“Indifference” is a new concept in Addiction Medicine, described for the first time by Olivier Ameisen as “bottles of alcohol don’t talk to me anymore” and is often not really understood. It is characterized by a complete eradication of obsessional thoughts about alcohol and, as a consequence, a drinking pattern that becomes effortlessly moderated to reasonable levels or to an abstinence which is freely chosen. As Ameisen described, “I am not forcing myself to remain abstinent, I just don’t feel like drinking anymore”. Indifferent AUD patients don’t need to work at reducing their alcohol consumption. Quite simply, they no longer feel the urge to drink: their addiction has disappeared.
People with AUD who have been successfully treated with baclofen will have drinking patterns identical to non-AUD individuals. A study released on the baclofen forum internet site baclofene.org , showed that about 30% of both groups chose to drink alcohol very rarely or not at all, 60% drank alcohol occasionally and the others more regularly but at safe levels (WHO criteria of less than 14 standard drinks per week in women and less than 21 drinks per week for men).
Indications and Contraindications
Baclofen is indicated for all forms of alcohol use disorder, whichever its form, abuse or dependence, occasional or continuous. Baclofen is indicated whether the aim of the patient is a complete abstinence or a simple reduction of alcohol consumption. Baclofen is also indicated in all medical illnesses resulting from chronic alcohol overconsumption, such as cirrhosis. Baclofen has no absolute contraindications except true allergy. Baclofen treatment is not recommended in patients with certain rare inherited diseases of the carbohydrate molecules, glucose and galactose or in patients with lactase deficiency or intolerance to galactose. Besides, there are a number of clinical conditions, e.g. obstructive sleep apnoea and renal insufficiency, that must be thoroughly evaluated with the patient before treatment initiation, in order to minimize the risk of adverse events and medical morbidity .
Information for Patients
The aim of baclofen treatment in AUD is that the patient becomes indifferent to alcohol. That means that the desire for alcohol no longer dominates thought processes. With time, thoughts about alcohol become like any other thought, passing through the patient’s mind then disappearing. The aim is that ultimately, the patient will feel free of the compulsion to drink. This means it is no longer necessary to demand strict, lifelong abstinence when treating AUD.
Baclofen is an old medication which has been prescribed for over 40 years. It has been used to reduce “spasticity”—the muscle spasms which occur when muscles are partly or completely paralyzed—for example in a paraplegic patient with paralyzed legs. Because baclofen has been used to treat patients for many decades, we know a lot about baclofen’s side effects and its effects in long term treatment , as explained later in this article. There is also information on baclofen prescribed at high doses as well as baclofen’s potential effects when taken with alcohol . This means that we have a good idea of what to expect with baclofen treatment.
The dose of baclofen needed to reach a state of “indifference” to alcohol is not a standard dose but is individual to each patient. The effective dose is found by assessing the patient’s reactions and changes during the treatment as the dose is increased over time. The patient will be able to tell when s/he is at the right dose. It is impossible to predict in advance whether side effects will occur during treatment or what dose of baclofen will be needed to reach for effective treatment.
It’s very important to stick to a steady, progressive increase in the baclofen dose to minimize the unpleasant side effects which happen when the dose is increased too rapidly.
The unpleasant side effects of baclofen are well known but not everyone gets them. The patient may have no side effects at all or, in contrast, have multiple side effects that can be mild or severe in nature. Their evolution over time is variable but overall, they tend to improve with time. In any case, they all completely disappear if the baclofen dose is reduced or treatment is ceased.
To summarize the treatment protocol for baclofen in AUD:
Progressively increase the baclofen dose until the effective dose is reached, which will be individual for each patient. This effective dose can be defined in a few different ways: indifference to alcohol (“bottles of alcohol no longer speak to me”) or the absence of craving for alcohol—the loss of the desire to drink or the disappearance of all ideas to obtain alcohol where previously this would have been an obsession.
Stay on the effective baclofen dose for a number of months in order to consolidate the positive response obtained by the treatment.
Then very slowly decrease the dose over a period of time which may last many months or many years, watching carefully for any reappearance of cravings, in which case the dose should be increased back up again.
The long-term aim is to stop the baclofen treatment which should be possible once the new pattern of cessation of uncontrolled drinking has been established for a long enough time.
The titration of baclofen involves increasing the dose slowly and progressively. There is no set way to do this. The pattern of dose increases will vary between baclofen prescribers who will have their own ways of doing the titration and will vary between individual patients: how independently they normally function, their wishes, how much they want to guide their own treatment and what other health problems they already have.
The most commonly used titration protocol for baclofen, the one that we recommend, is to increase the total daily dose of baclofen by one tablet of 10mg every three days. This is adjusted according to how the patient feels, particularly according to whether side effects appear.
The titration regime continues by continuing additions of 10mg to the total daily dose until the effective dose for that individual is reached. This is the dose at which there is a complete suppression of cravings, i.e. “indifference”. The patient will recognize when the effective dose has been reached.
The titration regime is adjusted for each patient and guided by the reaction to the treatment. If the patient doesn’t tolerate baclofen well, for example has side effects which are unpleasant, the increases in dose must be slowed down: by increasing the dose by 10mg only every 4-5 days, every 7 days, every 10 days or even by longer periods of time. Alternatively, the dose can be increased by 5mg (half-tablet) rather than 10mg.
If side effects are really unpleasant, further dose increases must be avoided. Either the patient can stay at the same dose at which the side effect appeared, knowing that side effects always tend to decrease with time, or the dose can be decreased back down to the previous dose at which this side effect did not occur. Once the side effect has settled, the patient can continue to increase the baclofen dose but more slowly and/or use smaller dose increases e.g. 5mg rather than 10mg.
Some patients increase their baclofen dose more rapidly than recommended, especially if they experience few or no side effects and are strongly motivated to reach their effective dose quickly. Increasing the dose rapidly will allow patients to reach their “indifference” dose faster. It also avoids patients becoming discouraged by the sometimes long period of titration needed, during which there is little positive effect on their AUD. However, overly rapid titration can also lead to patients experiencing abrupt, severe adverse effects. Therefore most prescribers recommend not to raise the baclofen dose too rapidly, even when it is well tolerated.
The doctor: patient relationship, the “therapeutic alliance”, is of critical importance in baclofen treatment. The patient needs to take an active role in treatment, under the guidance of the prescriber. The patient must inform the prescriber of what effect the baclofen treatment is having and therefore whether the dose should be increased, decreased or kept at the current level.
The effective dose varies between individuals and cannot be predicted in advance. There appears to be no correlation between the effective dose and factors such as patient weight, gender, height or how long they have suffered from an AUD. Nevertheless the effective baclofen dose seems to correlate with the severity of the alcohol dependence . But overall, it is impossible to predict in advance what the effective dose will be. Each patient is unique.
The clinical trials show that the average effective dose needed is around 140-180mg/day with a wide range from 10mg/day to 500mg/day or even more [7-11]. Two patient surveys done by the Baclofen Association in August 2013 and September 2015 showed the same results, with an average dose of 170-180mg/day and the same wide dose range . Importantly, it’s how the patient feels which guides the rate of dose increases and decides the final dose needed for effectiveness.
With regard to drinking alcohol alongside the baclofen titration, experience shows that it is not necessary to detox before starting baclofen treatment, although we have noted that starting treatment with a detox can reduce the final baclofen dose needed. Deciding whether to start baclofen treatment with a detox or not should be discussed by the patient and doctor. If an initial detox is to be carried out, it is worth remembering that the abrupt cessation of alcohol (as for baclofen also) will lower the seizure threshold.
The prescribing doctor can suggest that the patient voluntarily moderates his/her alcohol intake during the first weeks of baclofen treatment, until the state of indifference occurs. This can also help the patient to feel more actively involved in the treatment. In no longer seeking out social occasions for drinking, s/he comes to realize the habits and rituals around alcohol and can change them while looking to use things other than alcohol to face life’s stresses.
To summarize, the titration phase aims to get the patient up to the effective dose of baclofen that induces a state of indifference towards alcohol. The upward titration of the dose requires regular adjustment of the amount and timing of the daily doses.
In this phase, the patients’ feedback and the therapeutic relationship between patient and prescriber will guide the treatment.
Baclofen treatment needs to be adapted to each patient’s drinking pattern i.e. targeted to the times when patients feel cravings for alcohol. There are patients who start drinking from the morning, others who start only around midday or in the afternoon and others who only drink in the evening, without feeling a desire to drink over the rest of the day. Experience has shown that it’s generally not useful to take baclofen during the parts of the day in which there is no desire to drink. However this is not an absolute rule: later in this protocol, another regime will be described, that of “saturation”.
If a patient drinks each day between 6pm and 11pm but the first strong cravings start in the middle of the morning, the doses should start in the morning. It’s important to ask patients who drink only in the evening if this is also the case on the weekends. If on weekends they start drinking in the morning or any time before the evening, it is the time which craving starts on the weekend that should be used to determine the timing the first dose of the day for all days of the week.
To understand why it is important to target baclofen doses to times of cravings, it helps to understand how baclofen is processed in the body. It is rapidly absorbed by the intestines and diffuses throughout the body. The maximum level of baclofen in the blood occurs between 30 minutes and 90 minutes (0.5-1.5 hour) after taking the tablets. Baclofen is passed rapidly out of the body and by 3.5 hours, only half of the baclofen taken is still in the body (the “half-life”). At a practical level, this means that the action of baclofen will start rapidly but then decrease after about 4 hours. This means that baclofen needs to be taken multiple times a day (Figure 1).