Baclofen as a Pharmacotherapy for the Treatment of Concurrent Alcohol and Nicotine Dependence: A Double-blind, Placebo-controlled, Randomized Trial (Neuropsychopharmacology, 2014)
Autoren: Mehdi Farokhnia, Steven M. Edwards, Jared Bollinger, Jonathan Amodio, William H. Zywiak, Jennifer W. Tidey, Robert M. Swift, George A. Kenna & Lorenzo Leggio
(pp, 27.07.2015)
Struktur des Inhalts
Abstract im englischen Original
Background: Alcohol and nicotine use frequently co-occur and up to 75% of alcoholic smokers would require treatment for both dependencies. However, there is presently no approved single treatment that addresses both addictions concurrently. Combination of alcohol and nicotine provides additive neurochemical effects, which potentiate reinforcement for both substances and results in increased dopamine release in the nucleus accumbens. By stimulating GABAB receptors on the cell bodies of dopaminergic neurons and on the terminals of glutamatergic afferent neurons, baclofen may inhibit dopamine neurotransmission and, in turn, dopamine-mediated behaviors. Different clinical and preclinical studies suggest that the GABAB receptor agonist baclofen may be an effective pharmacotherapy for alcoholism or smoking, but no studies have investigated its effect in concurrent alcohol and cigarette use, which was the aim of the present study.
Methods: In this double-blind placebo-controlled randomized clinical trial, 30 treatment-seeking alcoholic smokers were randomized to receive either baclofen (80 mg/day) or placebo for 12 weeks. A sub-group of patients (n=18) participated in an alcohol cue-reactivity experiment as well. To be eligible, participants had to have DSM-IV diagnoses of both alcohol and nicotine dependence in addition to heavy use of both alcohol (≥4 and ≥5 standard drink units per day on average for women and men, respectively) and nicotine (≥10 cigarettes per day on average) during the last 90 days before screening. Patients were visited 7 times during the treatment phase. Measurements of alcohol and nicotine use (Timeline Follow-Back) and craving (various questionnaires) were taken at each visit.
Results: Baclofen-treated patients experienced significantly more decrease [Corrigendum, s.u.] in the percent days of abstinence from alcohol-tobacco co-use compared to the placebo group (p=.004). Baclofen effect was moderated by alcohol dependence severity as more severely alcohol dependent participants showed significantly greater response to that (p<.001). During the course of this study, the percent days of alcohol-tobacco co-use declined in both groups, but this decline was greater after placebo than baclofen (p<.001). Analyses of the single use of each substance did not reveal an effect of baclofen vs. placebo on duration of abstinence from alcohol or nicotine. Reduction of alcohol craving scores was not significantly different between the two groups. By contrast, baclofen significantly reduced cigarette craving measured by Questionnaire on Smoking Urges-Brief (p=0.02) and slightly reduced the Smoking Visual Analogue Scale scores (p=0.05). Additionally, baclofen slightly decreased alcohol urge (p=.05) and significantly reduced salivation (p=.001) in the cue-reactivity sub-study although no medication × cue type interaction was found.
Conclusions: Baclofen’s effects on alcohol sensitivity and nicotine reinforcement may have been responsible, respectively, for the ability of baclofen to reduce drinking and smoking in this population of alcoholic smokers. Co-administration of alcohol and nicotine results in increased dopamine release, which may be blocked by baclofen, thus resulting in its ability to promote abstinence from both substances. Here we found that baclofen was more effective in increasing the days of abstinence from alcohol-tobacco co-use in those patients with a greater degree of alcohol dependence. In summary, this study provides preliminary evidence suggesting the potential efficacy of baclofen in the treatment of alcoholic smokers. However, the mixed results and the small sample require larger confirmatory studies.Corrigendum: The first sentence in the ‘Results’ section should be ‘Baclofen-treated patients experienced significantly more increase in the percent days…’ (Neuropsychopharmacology (2015) 40, 1560)
Link zum englischen (Poster)Volltext (Es handelt sich um Poster T76)
