This study was featured on Findings from earlier this year:
From Germany the first trial to rigorously test high doses of the muscle relaxant baclofen for the treatment of dependent drinking found post-detoxification drinking reductions of a magnitude rarely seen; safety issues remain, but it seems these can be managed with close monitoring and individualised dosing.
In the USA and Europe few medications have been approved for the treatment of dependent drinking: disulfiram, acamprosate, nalmefene, and naltrexone oral and injectable. Some have repeatedly been found effective in rigorous clinical trials, but effects have been modest – there is room for improvement through additions to this range.
One possible addition is baclofen, a medication taken by mouth as tablets. The drug relaxes muscles and is approved for preventing muscle spasms resulting from neurological conditions. The few trials which have randomly allocated alcohol-dependent patients to baclofen versus placebo have found patients can take the drug without experiencing deterrent side effects (ie, they ‘tolerated ’ the drug well), but also found inconsistent impacts on drinking. Given its low ability to cross the blood-brain barrier, these might be related to the low doses of baclofen (30mg to 80mg per day) used in the trials.
Against this background, researchers decided to test high-dose baclofen (up to 270mg a day in three daily doses) for the treatment of alcohol dependence by randomly allocating 56 patients seen at a psychiatric centre in Berlin to the medication or to an inactive placebo. Patients and research assessors were not told which patients were taking baclofen, an attempt to eliminate expectation effects and leave only the effects of the medication. To join the trial, patients had to be adults dependent on alcohol who had just completed a medically managed withdrawal from alcohol (detoxification) and who were not legally required to attend for treatment nor suffering serious psychiatric problems. Averaging in their late 40s, about 70% were men. Most were employed and had close family who had been dependent on alcohol. Before treatment they were very heavy drinkers, averaging 199g alcohol per day, nearly 25 UK units.
The 24-week trial consisted of four phases. For up to the first four weeks, doses of baclofen and placebo were increased to a maximum 270mg a day depending on how well the patient tolerated the dose. Then the dose was maintained for 12 weeks before being tapered to zero over the next four weeks, after which patients were followed up for another four weeks. Tapering was instigated prematurely if patients started drinking. Patients were scheduled to visit the clinic from 13 to 17 times, where they were offered nine sessions of structured, supportive clinical care intended to influence them to take the medication as intended.
Abstinence from drinking was the main outcome assessed, based not just on the patients’ accounts but also breathalyser and blood tests. At the end of the trial just five patients could not be followed up. On the assumption that patients who left the study had relapsed to drinking, all 56 were included in the analysis of outcomes.
The authors’ conclusions
Individually adjusted, high-dose baclofen supported alcohol-dependent patients in maintaining abstinence and was well tolerated, even when patients resumed drinking, results which might extend pharmacological treatment options. Compared to previous studies, baclofen doses were relatively high, possibly why it was more effective than placebo in this study but not in a larger US trial which prescribed 30mg a day. The drug’s impacts do not seem to depend on reaching a set dose, so dose can probably be individually adjusted without jeopardising effects on drinking.
Findings suggest baclofen does not work primarily by reducing craving or anxiety. Another suggested mechanism is substituting for alcohol by producing similar effects, yet in this study no patient reported alcohol-like effects, or craving or withdrawal symptoms after the drug was withdrawn.
Results confirm the good safety profile of baclofen found in previous trials, though lack of data on safety at high doses demands care and close monitoring; in this study about two-thirds of the baclofen patients (but just a third prescribed a placebo) did not reach the maximum 270mg per day dose. Alcohol-dependent patients with psychiatric conditions have been known to take dangerously high doses of baclofen to induce intoxication, suggesting extra care before prescribing it to alcohol-dependent patients with psychiatric conditions and/or who have previously attempted suicide.
Despite clear-cut results favouring baclofen, the study’s sample was too small to be definite about the drug’s future role in the treatment of alcohol dependence, and the study was conducted at a single site; elsewhere results might differ. Only abstinence was assessed, not whether baclofen curbs drinking in patients who continue to drink.
As the Findings commentary said: “It is rare for any medication or psychosocial therapy to register such large impacts. But while the abstinence gap between baclofen and placebo patients was large, it seems this reflected poor outcomes among the placebo patients as much or more than the good performance of baclofen.” So although the results were good this is because it fared well against the placebo, which in the case of alcohol dependence, it appears had little or no effect, which is unsurprising.
It went on to say “The authors’ caution that more needs to be known about the safety of high doses of baclofen – and especially so among heavy drinkers – is an important consideration. Baclofen is not licensed in the UK for the treatment of alcohol dependence, though it has been used by some clinicians.”
And “The UK’s prescribing guide warns that taking baclofen while drinking can magnify alcohol’s effects. An account of baclofen-induced intoxication among alcohol-dependent emergency department patients in France indicates that fatal overdose is a risk when high doses of baclofen are taken in the presence of other drugs which depress the nervous system, including alcohol and benzodiazepine tranquilisers.”
I read all of that and feel that these are the very early days of trialling and I would be reluctant to take Baclofen personally based on these findings. If anyone reading this has taken Baclofen and would like to share their experience I’d love to hear it 🙂
Edited to add: 8th October 2016