Baclofen as Add-On to Standard Psychosocial Treatment for Alcohol Dependence: a Randomized, Double-Blind, Placebo-Controlled Trial With 1 Year Follow-Up Alexander M. Ponizovsky, M.D, Ph.D a, ⁎, Paola Rosca, M.D b , Edward Aronovich, Ph.D c , Abraham Weizman, M.D d , Alexander Grinshpoon, M.D, Ph.D e a Research Unit, Mental Health Services, Ministry of Health, Jerusalem, Israel b Department for the Treatment of Substance Abuse, Ministry of Health, Jerusalem, Israel c Computer Sciences, Tel Aviv University, Tel Aviv, Israel d Research Unit, Geha Mental Health Center, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv,Israel e Sha'ar Menashe Mental Health Center, Bruce Rappaport Medical Faculty, Technion, Haifa, Israel abstract article info Article history: Received 11 June 2014 Received in revised form 18 November 2014 Accepted 24 November 2014 Keywords: Baclofen Alcohol dependence Clinical trial Background: Limited clinical trials and case-reports yielded conflicting results regarding the efficacy of baclofen (a GABAB agonist) in the treatment of alcohol dependence. The aim of this study was to test the efficacy and tolerability of baclofen in alcohol dependent patients in Israel. Methods: The study was a double-blind, placebo-controlled, randomized trial comparing 50 mg/day of baclofen to placebo over 12 weeks, in addition to a standard psychosocial intervention program, with 26-week and 52-week follow-up observations. The percentages of heavy drinking days and abstinent days were the primary outcome measures, and craving, distress and depression levels; self-efficacy; social support from different sources; and health-related quality of life (HRQL) were secondary outcomes. Tolerability was also examined. Results: Sixty-four patients were randomized; 62% completed the 12-week trial and 37% completed the 52-week follow-up. No between group differences were found in the percentages of heavy drinking and abstinent days. A significant reduction in levels of distress, depression and craving and improved HRQL occurred for both arms, whereas self-efficacy and social support remained unchanged in both groups. No adverse events were observed. Conclusions: Unlike previous positive trials in Italy, and similarly to a negative trial in the USA, we found no evidence of superiority of baclofen over placebo in the treatment of alcohol dependence. However, the high placebo response undermines the validity of this conclusion. Therefore, more placebo-controlled trials are needed to either verify or discard a possible clinical efficacy of baclofen for alcohol dependence. © 2015 Elsevier Inc. All rights reserved. 1. Introduction Among pharmacological agents for the treatment of alcohol depen- dence that have demonstrated some efficacy in reducing alcohol withdrawal symptoms as well as alcohol craving and relapse rates (Müller et al., 2014; Zindel & Kranzler, 2014), baclofen takes a particular place (Addolorato, Caputo, Capristo, et al., 2002; Addolorato, Leggio, Abenavoli, et al., 2006, Addolorato, Leggio, Agabio, et al., 2006; Addolorato, Leggio, Ferrulli, et al., 2007; Bucknam, 2007) because the medication is widely prescribed off-label in alcohol dependence, al- though evidence for its recommendation is insufficient (Liu & Wang, 2013). Baclofen—a potent, stereoselective Υ-aminobutyric acid B (GABAB) receptor agonist—proved to be effective in suppressing alcohol withdrawal signs in alcohol dependent patients both in open-label and controlled clinical trials (Muzyk, Rivelli, & Gagliardi, 2012). Moreover, baclofen was found to be effective in relapse prevention due to its ability to maintain abstinence from alcohol reducing alcohol craving and consumption in alcoholic patients (Addolorato, Leggio, Abenavoli, et al., 2006; Addolorato, Leggio, Agabio, et al., 2006; Addolorato et al., 2002; Addolorato et al., 2011; Brennan, Leung, Gagliardi, et al., 2013; Bucknam, 2007; Colombo, Addolorato, Agabio, et al., 2004; Cousins, Roberts, & de Wit, 2002; Flannery, Garbutt, Cody, Renn, et al., 2004; Heilig & Egli, 2006; Johnson, Swift, Addolorato, et al., 2005). Baclofen (brand names Kemstro and Lioresal, manufacturer Parhhem Trading, Ltd.) is a muscle relaxant and antispastic medicine, whose primary indication is the treat- ment of spasticity resulting from a number of degenerative neurological disorders, including multiple sclerosis (Davidoff, 1985). Adverse events associated with baclofen use (drowsiness; dizziness; weakness and fatigue; confusion; insomnia; hypotension; nausea; constipation, and urinary frequency) have generally been transient and are of mild-to- moderate severity (Garbutt, Kampov-Polevoy, & Gallop, 2010; Muzyk et al., 2012). The central nervous system depressant effects of baclofen may be additive to those of alcohol and other central nervous system (CNS) depressants. Importantly, in previous clinical trials baclofen proved Journal of Substance Abuse Treatment 52 (2015) 24–30 ⁎ Corresponding author at: Mental Health Services, Ministry of Health, 39 Yirmiyahu St., PO Box 1176, Jerusalem 9446724, Israel. E-mail address: alexpon8@gmail.com (A.M. Ponizovsky). http://dx.doi.org/10.1016/j.jsat.2014.11.007 0740-5472/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Journal of Substance Abuse Treatment Downloaded from ClinicalKey.com at Inova Fairfax Hospital - JCon January 08, 2017. 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