Clinical Case Study
Front. Psychiatry, 10 October 2014 | doi: 10.3389/fpsyt.2014.00143
Renaud de Beaurepaire*
Groupe Hospitalier Paul-Guiraud, Villejuif, France
Baclofen, particularly high-dose baclofen, has recently emerged as a treatment of major interest for alcohol-dependence. However, baclofen has many potentially dangerous side effects, and the maximal dose of baclofen that may be used is a matter of discussion. Here, the author analyses the medical charts of the last 100 patients seen in his clinic, 17 of whom have been taking a very high dose of baclofen, which is to say, more than 300 mg/day. The analysis of the charts shows that the very high-doses baclofen were justified in almost all the cases. Side effects are analyzed.
Introduction
High-dose baclofen has been shown to produce a remarkable state of indifference toward alcohol (1). However, the question of the upper limit of baclofen dosage that may be reached is a matter of discussion. Drug summaries recommend not exceeding the daily dose of 75–80 mg (75–80 mg/day) (2, 3) although long-term studies have shown that doses exceeding 250 or 300 mg/day are often necessary to produce a state of complete indifference to alcohol (4, 5). Recently, the French Health Safety Agency released a recommendation allowing for the prescription of baclofen to be given up to 300 mg/day, but not beyond, for the treatment of alcohol dependence (French Ministerial decree of June 13, 2014).
The present report is an analysis of the author’s medical charts of patients taking, or having taken, very high doses of baclofen, i.e., more than 300 mg/day for the treatment of their alcohol dependence. Since 2008, the author has prescribed baclofen to approximately 600 alcohol-dependent patients. The charts of the last 100 patients, followed for at least 6 months, were reviewed. At the time of the review (July 2014), all the patients except one (see Patient-14 below) were under the care of the author (last visit posterior to May 2014). Among the 100 charts, it appeared that 17 patients have been taking doses of baclofen superior to 300 mg/day at 1 time or another during their treatment (7 other patients reached the dose of 300 mg/day without exceeding it). This means that, according to this cohort, 17% of alcohol-dependent patients need more than 300 mg/day of baclofen for their treatment (and nearly one in four needs at least 300 mg/day).
The treatment was conducted similarly for all patients; doses were progressively increased (one additional 10 mg-tablet every 3 days) until a state of indifference toward alcohol (suppression of craving) was reached. After reaching a dose of 120–150 mg/day, if these doses were ineffective, or not sufficiently effective, patients were asked to actively participate in the dose increase. They were told that, unless they have no unbearable side effects, they must continue to increase the dose of baclofen, with no given limit of dosage, as long as they have episodes of craving for alcohol. In case of unbearable, or difficult to bear, side effects, they were told to slow the progression of the increase, or to decrease the dose until the side effect either disappears or becomes bearable, and then once again increase the dose, possibly much more slowly (one tablet, or a half-tablet, every week or 10 days, or possibly even more slowly). Patients were thereby trained to manage by themselves the increase of the doses according to a principle of self-involvement in the management of their treatment, while always under strict medical control (monthly visits, phone call to the author whenever necessary).
Background
In previous reports of clinical cases of baclofen in alcohol-dependence patients were always treated with doses beneath 300 mg/day (1, 6–8).
Clinical cases
Clinical cases are presented below (see also Table 1). Patients are classified according the length of their follow-up, from the longest to the shortest. Side effects will be considered in a separate paragraph in the Section “Discussion.”
Patient-1
Patient-1 (Pt1) is a 58-year-old healthy farmer drinking approximately three or four bottles of wine per day (he denied drinking, hiding bottles in the bush). He was brought in our clinic by his family, and did not seem to be very motivated to stop drinking. He was forced to take the baclofen treatment, given authoritatively by his wife, and rapidly drank much less (at 120 mg/day), but nevertheless continued to drink to excess (on the sly), as evidenced by biological measures. He stopped drinking at 210 mg/day (normalization of hepatic enzymes). After a year or two, he decided he was cured, stopped baclofen, and relapsed a few months later. Baclofen was restarted but the dose of 210 mg was insufficient. Doses were then increased (in large part driven by his daughter who was a pharmacist) and he was taking 360 mg/day at the time of his last visit (June 2014). According to the family, he has no craving at all, not drinking even when he is offered a glass of wine.
Patient-2
Patient-2 (Pt2) is a 28-year-old salesman drinking one to two bottles of whiskey per day (4–8 20 cc whiskey flasks), and a variable number of beers. He is emotionally very unstable, impulsive, abuses cannabis, and has a long history of anxiety and depression for which he has previously been treated but he was taking no psychotropic medications (except benzodiazepines) when baclofen was started. The road to abstinence with baclofen turned out to be very long and chaotic, with nearly 4 years of ups and downs. Baclofen was initially very effective; he stopped drinking completely at 120 mg/day but started drinking again after a month or two, beer only. He later turned to sparkling wine for several months. He alternated periods of sobriety, periods of moderate drinking (one bottle of sparkling wine or some beer) and short episodes of massive drinking during the following years. He acknowledged that baclofen greatly reduces his craving, and he has progressively increased it over the years, reaching the dose of 320 mg during some months in 2013. But his daily treatment compliance was irregular (often off-schedule). He is now (June 2014) taking 300 mg/day regularly, he says, and drinks an average of two or three beers per day. He is still impulsive and equally emotionally unstable and is still cannabis-dependent (although his consumption of cannabis has substantially decreased).
Patient-3
Patient-3 (Pt3) is 59-year-old woman referred for an intractable alcoholism (4 bottles of white wine per day) associated with a fronto-temporal dementia. The dementia was labeled idiopathic by her neurologist, independent of the alcoholism. She is treated by clomipramine and donepezil. Baclofen was considered by the family as a last-resort attempt. Increasing baclofen doses proved to be extremely difficult due to the massive memory problems of the patient and to insufficient surveillance of treatment administration by the (very busy) family. It took 2 years to reach the dose of 400 mg/day (thanks to an ancillary worker who was hired by the family to accompany the patient and control her treatment observance). At that dose, the patient suddenly stopped drinking, showing a total indifference toward alcohol. Two years later, she is still sober (ritually filling at dinner time a glass of wine, which she does not finish), and has recovered fairly good memory capacities (the diagnosis of idiopathic dementia has been abandoned).
Patient-4
Patient-4 (Pt4) is 32-year-old technician drinking one bottle of rum every day. He suffers from a severe anxiety disorder, with agoraphobia and emotional instability (treated with an antidepressant and an atypical antipsychotic). He became almost completely abstinent at 200 mg/day (although not completely indifferent to alcohol), but had episodes of relapse due to stress and instability (mainly in relation to conflicts in the workplace, a divorce and concomitant painful somatic illness). He shifted from rum to beer, and increased baclofen doses at each relapse, reaching the dose of 520 mg/day. He is presently stabilized at 320 mg/day, does not drink and says he has no craving, although still having brief episodes of massive alcoholization (an average of one every 2 months), when he drinks an entire bottle of rum and/or other drinks over 1 or 2 days.
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