Efficacy and Tolerability of Baclofen in Substance Use Disorders: A Systematic Review

Abstract

Background: It has been reported that baclofen, a drug used in the treatment of spasticity, reduces the severity of withdrawal symptoms and substance use disorders (SUDs) for some psychoactive drugs. Aims and Methods: To evaluate the effectiveness and safety of baclofen in the treatment of withdrawal syndrome and/or SUDs, providing (1) an outline of its pharmacological features; (2) a summary of studies that have suggested its possible effectiveness in the treatment of SUDs, and (3) a review of randomized, controlled trials (RCTs) on baclofen and SUDs. Results: Baclofen tolerability is generally considered to be good. Eleven RCTs investigated its effectiveness in the treatment of SUDs. Of these, 5 RCTs found that baclofen is effective, 5 RCTs found that it is ineffective and the results of 1 RCT were not appreciable because it did not achieve the preplanned level of participation. Conclusions: The number of RCTs on baclofen and SUDs is still low, and their results are divergent. Further RCTs should be undertaken, particularly with higher doses of baclofen. Its administration may be suggested in patients who fail to respond to other approved drugs or who are affected by liver disease that prevents their administration, or in patients affected by SUDs for which no approved drugs are available. Treatment should be conducted under strict medical supervision.

Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons

“…However, alcohol intake was similar across the five days of alcohol access, suggesting that aversive effects were not the primary factor in drinking reduction. Nevertheless, the duration of baclofen side effects observed in the present study is consistent with clinical reports suggesting that side effects of baclofen administration are generally transient and subside with continued treatment (Agabio et al, 2013). Clinical trials have reported that baclofen was well tolerated in heavy drinkers and alcohol-dependent patients (Addolorato et al, 2002, 2007, 2011; Müller et al, 2015; Ponizovsky et al, 2015), although treatment efficacy has been mixed.…”

Death of an Alcohol-Dependent Patient following Intentional Drug Intoxication: Implication of Baclofen?

“…As suggested by Agabio et al [31], the safety and efficacy profile of baclofen used at very high doses for the treatment of alcohol dependence warrants further clinical investigations. The data provided by two ongoing studies (Alpadir and Bacloville - with baclofen at 180 and 300 mg per day, respectively) and future studies such as BacALD or BACLAD [26,27] will probably add considerable knowledge to the baclofen safety profile.…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Therefore, facilitation of the GABA system is being tested for the treatment of various drug addictions, with two main lines of approach. Stimulation of GABA B receptors reduces rewarding effects and consumption of several addictive drugs in various preclinical models (Roberts, 2005;Vlachou and Markou, 2010), but so far the results from the treatment trials on human addictions, especially on alcoholism, with the selective direct sedative agonist baclofen [(3R)-4-amino-3-(4-chlorophenyl)butanoic acid] have been inconsistent (Tyacke et al, 2010;Agabio et al, 2013;Brennan et al, 2013;Agabio and Colombo, 2014). To date, baclofen is the only GABA B receptor agonist approved in clinical use, in addition to g-hydroxybutyrate (see below).…”