The Journal of Neuroscience, 2 April 2014, 34(14): 5038-5043; doi: 10.1523/JNEUROSCI.4977-13.2014

Frontiers in Psychiatry, 03 December 2012

Renaud de Beaurepaire – Groupe Hospitalier Paul-Guiraud, Villejuif, France

Aims: The purpose of this study was to examine the long-term effects of baclofen in a large cohort of alcohol-dependent patients compliant to baclofen treatment.

Methods: A hundred patients with alcohol dependence, resistant to usual treatments, were treated with escalating doses of baclofen (no superior limit). Alcohol consumption (in grams) and craving for alcohol were assessed before treatment and at 3, 6, 12, and 24 months. Assessments were simply based on patients’ statements. The outcome measure was the consumption of alcohol, rated according to the World Health Organization criteria for risk of chronic harm.

Results: While all patients were rated “at high risk” at baseline, approximately half of them were rated “at low risk” at 3, 6, 12, and 24 months. The sum of patients who were at “low risk” and at “moderate risk” (improved patients) was 84% at 3 months, 70% at 6 months, 63% at 1 year, and 62% at 2 years. The constancy of improvement over the 2-years was remarkable. The average maximal dose of baclofen taken was 147 mg/day. Ninety-two percentage of patients reported that they experienced the craving-suppressing effect of baclofen. Significant relationships were found between the amount in grams of alcohol taken before treatment and the maximal dose of baclofen required, and between the existence of a mental disorder and a lesser effect of baclofen.

Conclusion: Baclofen produces an effortless decrease or suppression of alcohol craving when it is prescribed with no superior limit of dose. Potential limitations in the effectiveness of baclofen include the coexistence of a mental disorder, the concomitant use of other psychotropic drugs, a lack of real motivation in patients to stop drinking, and the impossibility to reach the optimal dose of baclofen because of unbearable side-effects (sometimes possibly related to too sharp a protocol of dose escalation).

Suppression of alcohol dependence using baclofen: a 2-year observational study of 100 patients

Neurology 1991;41 :1829-1831
Charles R Smith, MD ; Nicholas G LaRocca, PhD ; Barbara S.Giesser, MD and Labe C Sheinberg, MD.

Cet article écrit en 1991  montre l’emploi fréquent de hautes doses (>80mg/j) de baclofène dans le traitement de la spasticité.

Résumé de l’article – Nous avons examiné un échantillon aléatoire de 10%  des dossiers d’une clinique externe traitant la  sclérose en plaques afin de déterminer la fréquence avec laquelle le baclofène a été prescrit pour traiter la spasticité à doses élevées (> 80 mg / j). Environ 20% des patients avaient pris de haute dose de baclofène, et 15% recevaient encore une dose élevée. Prendre une dose élevée n’a pas été associée à l’arrêt du traitement.

Voici l’article original

High-dose oral baclofen : Experience in patients with sclerosis

Et sa traduction

Haute dose de baclofène par voie orale: expérience chez les patients atteints de sclérose

By Rehman Tungekar Jul. 05, 2011 – http://www.wbez.org/episode-segments/2011-07-05/drug-could-offer-respite-alcoholics-88719#

Baclofen was designed as a muscle relaxant. But a small group of physicians now prescribe it to patients suffering from alchoholism as a way to reduce patients’ craving for alchohol. Rehman Tungekar spoke with doctors and patients using the medication to help kick the habit. Rebecca agreed to meet in a quiet park, where there would be few people to overhear her speaking. Her real name isn’t Rebecca – she asked for an alias to be used. Rebecca’s been drinking since she was a teenager, but it was only in the past two years that she really began drinking excessively. “Oftentimes I would black out,” she recounted, “and every time I did it I would tell myself ‘Well, I’m not going to do that tomorrow night.’ And yet I did.”

In the past, Rebecca had tried Alcoholics Anonymous and even saw an addiction specialist, but it never seemed to be enough. “I think my drinking improved for a bit, but then it just kind of went back to drinking excessively,” she said, “so I really decided to start researching pharmacological agents to help with alcoholism.”

More : Baclofen Was Designed As A Muscle Relaxant

Traduction en français :  Le Baclofène est un relaxant musculaire

L’interview :

Dr. Olivier Ameisen has tried to persuade the medical community to test what he says is a highly effective cure for alcoholism: a decades-old muscle relaxant called baclofen. Now, a Dutch donor has given half-a-million euros to conduct a rigorous study of the drug. Is this a major step in improved addiction treatment? What other innovations are on the horizon?

Guests : Dr. Olivier Ameisen: US cardiologist born and raised in France, Visiting Professor of Medicine at State University of New York Downstate Medical Center and author of Heal Thyself, a book which documents his investigations into the use of baclofen in the treatment of alcohol dependence.
Dr. Omar Manejwala: Medical director of the Hazelden addiction treatment center in Center City, a psychiatrist and leading expert in addiction medicine whose practice includes a focus on addiction treatment for health care professionals.
Dr. Jon Grant: Professor of Psychiatry at the University of Minnesota and co-directs a clinic for Impulse Control Disorders at the University of Minnesota Medical Center

Emission radio

LA REVUE AMÉRICAINE « SCIENCE » CONSACRE UNE PLEINE PAGE AU LIVRE « LE DERNIER VERRE » D’OLIVIER AMEISEN AINSI QU’A SES TRAVAUX.
PARU LE 6 MAI 2011, L’ARTICLE RELATE LES 6 ANS DE COMBAT D’OLIVIER AMEISEN AFIN DE FAIRE RECONNAITRE LE BACLOFÈNE DANS LE TRAITEMENT DE LA MALADIE ALCOOLIQUE. SES APPELS REPETÉS ET RESTÉS SANS RÉPONSE POUR DES ESSAIS CLINIQUES A HAUTES DOSES… LE DON IMPORTANT D’UN PATIENT NEERLANDAIS GUÉRI PAR LE TRAITEMENT DÉCOUVERT EN LISANT LE « DERNIER VERRE »… ENFIN CE QU’OLIVIER AMEISEN PENSE DES ESSAIS EN COURS…

Science, revue américaine hebdomadaire publiée par « l’American Association for the Advancement of Science », est avec Nature la revue générale scientifique la plus vendue dans le monde, avec un lectorat total estimé à un million de personnes. Ces deux revues sont dans leur domaine les plus prestigieuses aussi.

L’article : Anonymous Alcoholic Bankrolls – Trial of Controversial Therapy

Sa traduction : Un alcoolique anonyme finance un essai clinique d’un traitement controversé

Par Addolorato G, Leggio L, Ferrulli A, Cardone S, Bedogni G, Caputo F, Gasbarrini G, Landolfi R -« Alcohol and alcoholism (Oxford, Oxfordshire). » 2011 May-Jun;46(3):312-7. Epub 2011 Mar 17

Aims: To explore the effect of baclofen in a dose of 20 mg three times per day, compared with the already studied dose of 10 mg three times per day, in the treatment of alcohol dependence.

But : explorer les effets du baclofène à la dose de 20mg trois fois par jour, comparé avec l’étude précédente à la dose de 10mg trois fois par jour dans le traitement de l’alcoolisme.

Methods: We present a secondary analysis of a 12-week double-blind, placebo-controlled, randomized clinical trial with two doses of baclofen, specifically 10 mg t.i.d. and 20 mg t.i.d. Out of 94 subjects consecutively screened, 42 were randomized into the study. Fourteen of the 42 patients were randomly allocated to placebo, 14 to the group treated with baclofen 10 mg t.i.d. (B10 mg) and 14 to the group treated with baclofen 20 mg t.i.d. (B20 mg).

Méthodes : Nous présentons une seconde analyse de 12 semaines en double aveugle, controlée par placebo avec deux doses de baclofene c’est à dire 10mg ou 20mg. Sur 94 sujets examinés consécutivement, 42 ont été iclus dans l’étude. Quatorze des 42 patients ont été inclus au groupe placebo, 14 dans le groupe traité avec 10 mg de baclofène et 14 dans le groupe traité avec 20mg de baclofène.

Results: Compared with patients allocated to placebo, patients allocated to the B10 mg group had a 53% reduction in the number of drinks per day (P < 0.0001) and patients allocated to the B20 mg group had a 68% reduction in the number of drinks per day (P < 0.0001), with respect to the number of drinks per day during the 28 days before randomization. The effect of baclofen 20 mg t.i.d. was greater than that of baclofen 10 mg t.i.d. (P = 0.0214, Wald test) showing a dose–effect relationship. Both doses of baclofen were well tolerated. Conclusion: This is provisional evidence of a dose–response effect for baclofen in the treatment of alcohol dependence.

Résultats : comparé avec les patients qui ont reçu le placébo, les patient du groupe B10 mg ont eu 53% de réduction du nombre de verres bus par jour et les patients du groupe B20 mg ont eu une réduction de 68% du nombre de verres consommés par jour, ce qui est plus que le groupe B10 mg, démontrant un effet dose dépendant.  Les deux doses de baclofène ont été bien tolérées

Conclusion: Ceci est une preuve provisoire d’un effet dose-dépendant du baclofène dans le traitement de dépendance à l’alcool

Kelsey Bock – School of Physician Assistant Studies. Paper 216. 2010

Background: Many people suffer from alcoholism which can be a debilitating disease. With only three medications on the market to treat alcoholism, research to find new pharmaceuticals is important. The recent publication of a book promoting baclofen, a GABA agonist normally used to treat spasticity, as a treatment for alcoholism, has brought public attention to the topic. For potential patients who have read the book and clinicians who treat alcoholism, this systematic review examines claims that baclofen decreases alcohol cravings and has a possible clinical use in the treatment of alcoholism.

Methods: An exhaustive search of available medical literature, published in English, was conducted using MEDLINE, Evidence-Based Medicine Reviews Multifile, and CINAHL with the keywords “baclofen” and “alcoholism.” A bibliographical search of the literature was done to find further articles and information. Each study needed to evaluate both abstinence and craving for alcohol. Due to the fact that there is limited research available on the topic, all available articles were included.

Results: The search yielded 2 random controlled trials, 2 open label studies, and 3 case reports. Both random controlled trials (RCT) showed statistically significant results in increased abstinence and decreased craving in baclofen versus placebo group. Both open label studies showed decreased craving with baclofen use, and one showed increased abstinence, while the other showed a decrease in alcohol consumption. All three case reports described accounts of severe alcoholics whose alcoholism was successfully treated with higher doses of baclofen. Minimal to no side effects were seen in all trials and no patients described craving or euphoric effects from taking baclofen.

Conclusion: Even with the need for more research on the topic, baclofen should be considered as another medication to try in the treatment of alcoholism. Patients with intense cravings for alcohol may have greater benefit in cessation of alcohol use as baclofen significantly and quickly decreases cravings. Both the high safety and low side effect profile make baclofen a reasonable option to try. Since the amount of research on the topic is minimalminimal, clinicians need to use their judgment and may want to try baclofen only after first attempting other treatment options. The duration and dosage of baclofen is uncertain and will need to be adjusted on a patient by patient basis.

The efficacy of baclofen in reducing alcohol consumption

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James C. Garbutt, Alexei B. Kampov-Polevoy, Robert Gallop, Linda Kalka-Juhl, Barbara A. Flannery – Alcohol Clin Exp Res. 2010 Nov;34(11):1849-57. doi: 10.1111/j.1530-0277.2010.01273.x.

Background: Recent clinical trials and case-reports indicate that baclofen, a GABA_B agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol-dependent individuals in 2 placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States.

Objet : Les éudes récentes et les “case report” indiquent que le baclofène, un agoniste du GABA-B peut être efficace dans la dépendance alcoolique. Il a été démontré que le baclofène pouvait  améliorer l’abstinence, réduire le craving, réduire la quantité de boisson  consommée, et réduire l’anxiété dans  la dépendance alcoolique dans les deux essais contrôlés par placebo en Italie. Cependant, les données des études cliniques concernant le baclofène sont limitées. L’objet de cette étude est de tester l’efficacité et la tolérance du baclofène dans l’alcoolo-dépendance aux états unis

Methods: The study was a double-blind, placebo-controlled, randomized study comparing 30 mg/d of baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low-intensity psychosocial intervention. One hundred and twenty-one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined.

Méthode : L’étude est en double aveugle, contrôlée par placébo, compare une dose de 30mg/jour de baclofène à un placébo durant 12 semaines de traitement  en ajoutant 8 sessions de BRENDA, un programme psychosocial. Sur 121 sujets, 80 sujets ont été répartis (44 hommes) avec une répartition équilibrée par sexe. La mesure principale était le pourcentage de jours de consommation abusive, le niveau d’anxiété et de craving étaient des résultats secondaires. La tolérance a été examinée

Results: Seventy-six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on-average rates were 25.5% (±23.6%) for placebo and 25.9% (±23.2%) for baclofen during treatment (t₇₃ = 0.59, p = 0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F_1,73 = 5.39, p = 0.02). Baclofen was well tolerated with only 2 individuals stopping baclofen because of adverse events. There were no serious adverse events.

Résultats : 66% de sujets ont complété l’étude. Aucune différence n’a été observée dans le pourcentage de jours de consommation abusive, 25,5% (± 23,6%) pour le placébo et 25,9% (± 23,2%) pour le baclofène pendant le traitement. De façon similaire, aucune différence n’a été observée en pourcentage de jours d’abstinence, en terme de prise dupremier verre, ou en terme de recommencer à boire de façon excessive. Le baclofène a été associée à une réduction significative de l’anxiété. Le baclofène a été bien toléré avec seulement 2 personnes arrêtant le baclofène en raison d’événements indésirables. Il ya eu aucun événement indésirable grave.

Conclusions: Baclofen, a GABA_B agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.

Conclusions : le baclofène, un agoniste du GABA-B, représente une possible approche médicamenteuse dans la dépendance alcoolique. Malgré des essais pré-clinique positifs en Italie, cette étude n’a pas pu démontrer la supériorité du baclofène versus placébo dans le traitement de l’alcoolisme. Une autre étude est nécessaire pour établir si oui ou non le baclofène a une efficacité thérapeutique dans la dépendance à l’alcool et quels sont les facteurs prédicifs de la réponse.