High-Dose Baclofen Supports Abstinence in Alcoholism

Pam Harrison

June 30, 2015

ATHENS, Greece — High doses of baclofen (multiple brands), a drug normally used to treat spasticity, supports alcohol-dependent patients in maintaining abstinence from alcohol and is reasonably well tolerated, new research indicates.

As reported by Philippe Jaury, MD, PhD, Université René Descartes, Paris, France, findings from the Baclofen for the Treatment of Alcohol Dependence (BACLAD) study showed that significantly more patients randomly assigned to receive baclofen remained abstinent during the 12 -week high-dose phase of the study than patients receiving placebo (68.2% vs 23.8%; P = .014).

The duration of cumulative abstinence during the same high-dose phase was also significantly higher in the baclofen group than in the control group receiving placebo (mean, 67.8 days vs 51.8 days; P = .047).

The number of dropouts during the high-dose interval did not differ between the baclofen and the placebo groups, although it was numerically lower in the baclofen group than in the placebo group (13.6% vs 23.8%).

Two patients in the baclofen group discontinued treatment because of side effects (fatigue), but the drug was well tolerated overall.

"When you go to Alcoholics Anonymous, people say to themselves, 'Today, I won't drink,' so alcohol is still in their mind, they just have to tell themselves that they are not going to drink today," Dr Jaury told Medscape Medical News.

"But with baclofen, abstinence is passive; when it works, thoughts of alcohol are not in your mind anymore. You can drink if you want to, but you can stop, and that's what has impressed me about this drug ― after patients start drug therapy, they tell me, 'I don't need to drink anymore, I don't like it,' and that was not their objective before they started treatment."

The study was presented here at the 12th World Congress of Biological Psychiatry and was published online April 13 in European Neuropsychopharmacology.

Anticraving Effects

The study included 56 patients. All patients had to be abstinent from alcohol on study entry.

Half of the participants (n = 28) were randomly assigned to an individually titrated baclofen arm at doses of 30 to 270 mg a day, and another 28 were assigned to placebo.

Patients were followed for 6 months.

The titration phase lasted for up to 4 weeks, depending on the individually tolerated high dose of baclofen; a high-dose phase lasted 12 weeks; a tapering phase lasted up to 4 weeks; and follow-up was conducted 4 weeks after termination of the study drug.

The mean dose of baclofen during the high-dose phase of the study was 180 mg a day. The maximum dose of baclofen allowed was 270 mg a day.

Adherence rates were high, at more than 85%, in both treatment arms.

Analysis spanning the titration phase, the high-dose phase, and the tapering phase of the study indicated that significantly more patients maintained abstinence in the baclofen group than in the placebo group (42.9% vs 14.3%; P = .37).

The duration of cumulative abstinence during the complete medication phase was also higher, although not statistically, at a mean of 82.9 days for baclofen patients vs a mean of 66.8 days for patients receiving placebo.

No serious drug-related adverse events were observed during the trial, even in the event of relapse.

"Baclofen has anticraving effects, it helps patients detach from alcohol effects and cues, and it probably has anxiolytic effects as well," said Dr Jaury.

However, its use was also associated with a large degree of intersubject variation, necessitating a careful and individually tailored approach to dosing and treatment, he added.

Side effects also vary widely among patients, the most common being drowsiness, fatigue, dizziness, gastrointestinal distress, and insomnia.

The key to minimizing side effects is to uptitrate the dose of baclofen extremely slowly, starting with 10 to 15 mg a day, increasing the dose to 30 mg 3 to 4 days later, and then by 10 mg every 3 to 5 days until the therapeutic dose is reached. The therapeutic dose varies widely from patient to patient.

Prescribing Guide

Having treated many alcohol-dependent patients with the drug, French physicians, including Dr Jaury, recently authored a prescribing guide for baclofen, which was published in the British Journal of Medicine and Medical Research (2014;4:1164-1174). "Experience has shown that it is not necessary for patients to be sober to start treatment with baclofen," Dr Jaury and colleagues write in the prescribing guide.

Indeed, Dr Jaury and colleagues have just completed BACLOVILLE, another randomized, placebo-controlled trial of the use of baclofen during the course of 1 year in alcohol-dependent patients.

This time, however, the study was carried out in "all comers," including patients who smoked cannabis, used heroin or cocaine, or who were mentally ill.

Results from BACLOVILLE are expected to be released by the end of 2015.

In his experience using baclofen to treat alcohol dependence, Dr Jaury said he has found that approximately 20% of patients can stop treatment and still remain abstinent or drink in a way that they can control.

If patients wish to stop treatment, the dose of baclofen should be slowly tapered, and patients should be counseled not to abruptly stop the drug, because they are likely to experience alcohol withdrawal symptoms.

"Physicians are slowly coming around to appreciate how good this drug can be, but every patient responds to treatment differently, and some patients need to take it five times a day, some need it once a day, so it's a difficult drug to prescribe," Dr Jaury said.

"But it's the first time in more than 40 years I have been taking care of patients with alcohol problems that they tell me they can drink a glass of champagne on special occasions and they don't need any more than a glass or two, or that when they see a bottle of wine in the market, they don't even think about wanting to buy it, so alcohol is no longer a parasite."

"You can think, you can do what you want to do, you can breathe, and that's the big difference with baclofen from any other treatment we've had for alcohol dependence."

Not Ready for Prime Time?

Asked to comment on the idea of using high-dose baclofen for the treatment of alcohol-dependence, Petros Levounis, MD, chair, Department of Psychiatry, Rutgers New Jersey Medical School, in Newark, and member of the American Psychiatric Association Council on Addiction Psychiatry, told Medscape Medical News that the idea that baclofen may have alcohol anticraving properties has been around for a long time.

"What has been lacking is substantial clinical research to show whether high-dose baclofen is truly helpful in the treatment of alcohol use disorder," said Dr Levounis.

Although the present study points in a favorable direction for baclofen, it is too small to allow drawing definite conclusions that would be clinically significant, he added.

"It is at best premature and at worst irresponsible and dangerous to tell patients who suffer from alcoholism that now you can drink if you want to but you can stop, because of presumed protection from baclofen," Dr Levounis cautioned.

Relapse rates for virtually all treatments for alcohol dependence range as high as 85%, and the effects from the few drugs that have been approved for alcohol dependence are exceedingly modest.

However, according to Dr Jaury, some 50,000 alcohol-dependent patients in France are currently receiving treatment with baclofen.

Dr Jaury and Dr Levounis report no relevant financial relationships.

12th World Congress of Biological Psychiatry. Abstract S-38:001. Presented June 15, 2015.

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