Volume 168, Issue 2, March 2010, Pages 159-162
doi: 10.1016/j.amp.2009.12.008 | How to Cite or Link Using DOI
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Remove dependency on alcohol and alcohol consumption by high-dose baclofen: an open trial
Suppression of alcohol dependence using high-dose baclofen: An observational study
W Ameisenhas, , and R. Beaurepaireb
a State University of New York Downstate Medical Center, New York, United States
b Centre Hospitalier Paul-Guiraud, 54 Avenue de la R?publique, 94806 Villejuif, France
Available online 8 February 2010.
Summary
This article reports the results of a test open for three months of baclofen in alcohol-dependent subjects. Baclofen was prescribed in increasing doses, with the upper limit 300 mg / day until the patients experience a reduction or elimination of their appetite for alcohol. The results show that three months, 88% of patients had completely stopped or significantly reduced their alcohol intake, and most of them have become indifferent to alcohol without effort. The doses of baclofen were required vary from one patient to another, ranging from 15 mg / day to 300 mg / day, with an average of 145 mg / day. About two thirds of patients required a dose greater than that allowed 80 mg / d.
Abstract
The present paper reports the results of An open 3-month trial of baclofen for the Treatment of Alcohol Dependence. Was prescribed baclofen at escalating doses, with 300 mg / day have set upper limit, up to the point at Which Patients Experienced DECREASE has gold deletion of Their motivation to drink. The results show That, at 3 months, 88 of the patients% HAD Either totally Stopped drinking, or HAD Significantly Decreased alcohol intake and Their Many of Them That HAD Become indifferent to alcohol, effortlessly. Efficacious doses Were Highly variable from patient to patient, Ranging from 15 mg / day to 300 mg / day (average 145 mg / day). Approximatelaly two thirds of the patients needed a dose approuv? Higher Than the 80 mg / day dose.
Keywords: Abstinence, Alcoholism, alcohol dependence, alcohol palatability; Baclofen
Keywords: Alcohol Dependence, Alcoholism, Baclofen; Motivation to drink
Article Outline
1. Introduction
2. Self-Observation
3. Baclofen
4. Discussion
5. Conclusion
Conflict of interest
References
1. Introduction
Alcoholism is a devastating disease for which there is still no truly effective drug treatment [7]. For twenty years, based on the idea that the "reduction" of craving could reduce the risk of relapse and thereby improve the prognosis of this disease in the United States alone is responsible for 100,000 deaths per year, a therapeutic model has been proposed [16] and [20]. This model makes use of therapeutic drugs called "anticraving", which include naltrexone, acamprosate, baclofen at low doses (30 mg / day), topiramate and ondansetron. All have proven their effectiveness in reducing craving in randomized clinical trials, but despite their use in multi-million alcohol-dependent subjects for nearly two decades [15], no reduction in mortality or morbidity of the disease of alcohol dependence has been reported.
2. Self-Observation
In 2004, one of us (Olivier Ameisen) postulates that, unlike what happens with other diseases, which suppress symptoms does not alter the prognosis of the disease (bacterial pneumonia, tuberculosis, coronary heart disease , etc..) in the addictions (including alcoholism) it might be sufficient to "suppress the symptoms of addiction to remove dependence" [4]. And the current model of "reduction" of craving may therefore be that "subtherapeutic." He noted that in all studies conducted in animals rendered dependent on alcohol, drugs anticraving above all to have ownership, at best, reduce the motivation of animals to consume alcohol, but only one of them, baclofen (which like other anticraving does at low doses that reduce the motivation) has however the unique property of removing the motivation from a threshold dose. This effect is dose-dependent [9]. The merit of the first description of an effect "canceling" the motivation to consume a substance in animals dependent by a molecule (baclofen) and the description of dose-dependent nature of this effect comes back to Roberts and Andrews who had described for cocaine in 1997 [18]. This unique property suppressive baclofen has subsequently been demonstrated for heroin, nicotine and d-amphetamine. Ameisen hypothesized that the suppressive effects of baclofen could be transposed to humans. It proposes a model in which translational therapeutic high-dose baclofen may remove any desire to consume alcohol in alcohol-dependent subjects. Himself a doctor and alcohol-dependent, and whose disease was refractory to all medical treatments led, after self-administered high doses of baclofen he publishes his own clinical cases of complete suppression of the disease of alcoholism by suppression of symptoms. He described that baclofen has made completely "indifferent to alcohol" and that "without the slightest effort." He contrasted this to the current model of abstinence that the patient requires constant effort to not drink, which not only dramatically alters his lifestyle, but also explains why over 80% of patients successfully detoxified and become abstinent relapse rapidly, as confirmed by a recent study [11]. Ameisen calls to test the therapeutic model of "suppression" (as opposed to mere "reduction") symptoms of alcohol dependence in randomized clinical trials of high dose of baclofen [4] and [5].
This is the first case reported in the literature of "suppression" of alcohol dependence in humans. It was reproduced following the same therapeutic model [3] and [8]. Baclofen had been tested in randomized clinical trials or open for over 15 years in alcohol-dependent subjects [1], [2], [10] and [13]. These authors, who all used the low dose of 30 mg / day (0.5 mg / kg) had reported that a "reduction" of craving, which therefore did not add baclofen no advantage over other drugs anticraving (naltrexone, acamprosate, topiramate, and ondansetron), for which purpose reducing the craving had been described. These clinical results are consistent with animal models in which baclofen begins to exert its suppressive properties as from 1 mg / kg.
3. Baclofen
Baclofen is used for over 40 years and received his permission to put on the market (AMM), with the only indication of neurological spasticity and what the maximum dose of 80 mg / day. From this amount, if spasticity is not adequately controlled, neurologists were required to use intrathecal who received his MA for spasticity refractory to oral baclofen 80 mg. The intrathecal present significant hazards and serious complications are frequently reported in literature (especially infectious). Number of neurologists experienced, to avoid exposing their patients to these complications - while spasticity is a disorder Benin and that baclofen is a treatment for comfort - prefer to use the oral baclofen high dose (> 80 mg / day), so off-label, up to 300 mg / day, that is to say until the desired effect is achieved as the patient tolerates the treatment [19 ].
Even in children, for balance disorders benign baclofen has been used for eight consecutive years, at a dose of 180 mg / day [12]. The safety of baclofen is considered particularly remarkable: a series of suicide attempts of 23 consecutive patients with massive doses of baclofen (up to 2.5 grams) was published. Among them, some just needed to be observed or treated in intensive care. Not a single death has occurred and all patients left the hospital without sequelae [14]. Furthermore, no cases of irreversible or severe complications during treatment with oral baclofen has been reported in the literature since the baclofen is used. Cases of severe complications reported all occurred when he was not used at high doses and oral off-label, but only when it was used as part of the MA intrathecally. The most common side effects of oral baclofen are drowsiness and muscle weakness, both reversible in 24/48 hours. For alcohol, the use of baclofen raised the problem it is therefore out of the WMA and could expose them to risks of adverse effects, the nature and severity are still poorly understood. What is however certain is that the side effects of the alcohol consumed in excess are well established and known to be extremely severe. Alcoholism is a very serious illness, a source of high morbidity and high mortality. It is therefore important to weigh the risk / benefit of treatment with a drug known as old and well tolerated with the evolution of a deadly disease for which there is no effective therapy. Denying a potentially effective treatment for patients is therefore equivalent to a loss of opportunity that can legally get them to turn against their doctor. According to the lawyer Odile Paoletti: "If, on the pretext that a drug has received marketing authorization, you do not prescribe to your patient, so he could improve his health or the curing Your liability could also be sought! " [17]. In other words, it could be a lack of ethics does not prescribe baclofen for alcohol-dependent individuals who request it.
We have therefore opted to prescribe increasing doses of baclofen, a compassionate approach to patients who had a long history of alcoholism treatment-resistant and made the step to come personally to ask this treatment. The requirements began in November 2008, following the publication in France of the book of one of us (Ameisen Olivier), a book that related the experience of self-medication of Olivier Ameisen by baclofen [6]. Following the publication of this book, many patients suffering from alcoholism called Olivier Ameisen, which sent the consultation of the other author of this article (Renaud de Beaurepaire), who conducted the treatment. The desire of some patients was able to completely discontinue their use and for others to regain control of their consumption. One of the diagnostic criteria for alcohol dependence is precisely this "loss of control of consumption" (DSM-IV, ICD-10).
4. Discussion
Baclofen has been prescribed in increasing doses (higher than 30 mg / week) until the patients experience a decrease or suppression of their appetite enough to make them indifferent to alcohol. Virtually all patients experienced a reduction or elimination of their palatability, but not all have decreased or stopped their alcohol intake. Sixty patients were followed for more than three months (the time deemed sufficient to assess the medium-term effectiveness of baclofen). At three months, they were classified into two categories according to their response to treatment:
? "success or goal achieved" (significant improvement of the control, elimination of dependence), corresponding to a complete stop taking alcohol, or taking a minimum and well controlled by them, or to a decrease of more than 50% of alcohol intake compared to before treatment. It should be noted that many patients in this category, have become "indifferent to alcohol" and that "abstinence" or reducing their intake of alcohol does not result "no effort" on their part to Unlike abstinence achieved with other treatments, which is the result of significant efforts and constant;
? 'failure', lack of control of consumption with no reduction in the consumption of drink.
The results show that three months 88% of the patients were categorized as "success", and 12% as "failure." The doses of baclofen were required vary from one patient to another, ranging from 15 mg / day to 300 mg / day, with an average of 145 mg / day. About two thirds of patients required a dose greater than that allowed 80 mg / day. There was nothing to predict the dose needed before treatment, this dose did not appear related to patient body size or with sex (but accurate analysis was not done).
Over 80% of patients reported side effects, for most minor and already described in all the aforementioned clinical trials of baclofen in the low dose of 30 mg / day. They should in no way constitute a limitation on the use of high dose of baclofen in these patients because they are weighed against the major side effects and often fatal alcohol, and that baclofen can delete or control the consumption of alcohol. The removal of alcohol dependence by the high-dose baclofen should be evaluated by randomized clinical trials. Approximately 20% of patients, because of these side effects, did not increase the doses to those that would probably have been necessary for a more effective impact. The most common side effects were somnolence, dizziness, insomnia, nausea / vomiting, digestive disorders, sensory disturbances, headaches and tinnitus. Several patients developed depression, which is difficult to say whether they were directly connected with baclofen or if they were related to psychological adjustments in connection with decreasing the desire to drink or if the alcohol had a function in these patients antidepressant that has disappeared with the decline of intoxication. The most likely occurrence is simply a psychological reaction to the awareness of very fast (sudden return of patients to clarity after years of intoxication) with sudden recognition of the catastrophic losses they suffered. An adverse event of concern was the occurrence of a state of mental confusion in several patients. Again, the relationship with baclofen is questionable since these are always mental confusion occurred in major stress situations, where patients over-consumption of alcohol and drugs (benzodiazepines), in addition to baclofen.
5. Conclusion
In conclusion, the results of this open study confirm that baclofen is the only drug able to completely remove the dependency on alcohol without effort by removing the motivation to consume alcohol. It has a considerable interest in the treatment of alcohol dependence, since it could greatly reduce the likelihood of relapse, although this risk is reduced by any of the other drugs in alcoholism and thus there is no effective treatment. Furthermore, doses well above those permitted are often necessary to obtain a suppressive effect of the disease. The mild side effects (sleepiness, dizziness, nausea) are the same as those described in clinical trials for baclofen 30 mg / day and placebo. They should in no way constitute a limitation on the use of high doses of baclofen in these patients because they are weighed against the major side effects and often fatal alcohol, and that baclofen can delete or control the consumption of alcohol.
Conflict of interest
None.
References
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