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Defining the Role of Baclofen for the Treatment of Alcohol Dependence

A Systematic Review of the Evidence

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Abstract

The pharmacological properties of baclofen, a GABAB receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety. We conducted a systematic review of prospective, randomized controlled trials comparing baclofen with placebo for the treatment of alcohol dependence. Four randomized controlled trials were identified but only three met criteria for inclusion. The excluded trial was a post hoc analysis of data collected from an original trial whose primary outcome did not fit our inclusion criteria and was terminated prior to completion. Compared with placebo, subjects randomized to baclofen experienced higher rates of abstinence and lower anxiety scores; the effect of baclofen was statistically significant in two trials assessing patients with more severe alcohol dependence and non-significant in a trial of outpatients receiving concomitant manualized psychotherapy. Baclofen appeared to be safe, well tolerated and to have low addiction liability even in the setting of moderate-to-severe liver cirrhosis, a known complication of alcohol dependence. Though baclofen may hold promise, the different outcomes and sample populations of the three studies highlight the need for more research to better understand the appropriate target patient population to benefit from this medication. Questions still remain about optimal dosing and duration. There is not enough evidence to support the use of baclofen as a first-line treatment option, except for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in whom other pharmacological treatments are not safe or practical.

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References

  1. Rehm J, Mathers C, Popova S, et al. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorder. Lancet 2009; 373: 2223–33

    Article  PubMed  Google Scholar 

  2. Hasin DS, Stinson FS, Ogburn E, et al. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States. Arch Gen Psychiatry 2007; 64: 830–42

    Article  PubMed  Google Scholar 

  3. Rehm J, Baliunas D, Guilherme B, et al. The relation between different dimensions of alcohol consumption and burden of disease: an overview. Addiction 2010; 105: 817–43

    Article  PubMed  Google Scholar 

  4. Rehm J, Taylor B, Mohapatra S, et al. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev 2010; 29: 437–45

    Article  PubMed  Google Scholar 

  5. Swift R. Emerging approaches to managing alcohol dependence. Am J Health Syst Pharm 2007; 64(5 Suppl. 3): S12–22

    Article  PubMed  CAS  Google Scholar 

  6. Mann K. Pharmacotherapy of alcohol dependence: a review of clinical data. CNS Drugs 2004; 18: 485–504

    Article  PubMed  CAS  Google Scholar 

  7. Garbutt JC, West SL, Carey TS, et al. Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA 1999; 281: 1318–25

    Article  PubMed  CAS  Google Scholar 

  8. Rosner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010; (9): CD004332

  9. Rosner S, Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010; 12: CD001867

    PubMed  Google Scholar 

  10. Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study. A randomized controlled trial. JAMA 2006; 295: 2003–17

    CAS  Google Scholar 

  11. Baltieri DA, Daro FR, Ribeiro PL, et al. Comparing topiramate with naltrexone in the treatment of alcohol dependence. Addiction 2008; 103: 2035–44

    Article  PubMed  Google Scholar 

  12. Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 2007; 298: 1641–51

    Article  PubMed  CAS  Google Scholar 

  13. Johnson BA, Ait-Daoud N, Akhtar FZ, et al. Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. Arch Gen Psychiatry 2004; 61: 905–12

    Article  PubMed  CAS  Google Scholar 

  14. Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomized controlled trial. Lancet 2003; 361: 1677–85

    Article  PubMed  CAS  Google Scholar 

  15. Caputo F, Addolorato G, Stoppo M, et al. Comparing and combining gamma-hydroxybutric acid (GHB) and naltrexone in maintaining abstinence from alcohol: an open randomized comparative study. Eur Neuropsychopharmacol 2007; 17: 781–9

    Article  PubMed  CAS  Google Scholar 

  16. Caputo F, Addolorato G, Lorenzini F, et al. Gamma-hydroxybutric acid versus naltrexone in maintaining alcohol abstinence: an open randomized comparative study. Drug Alcohol Depend 2003; 71: 85–91

    Article  Google Scholar 

  17. Gallimberti L, Ferri M, Ferrara SD, et al. Gamma-hydroxybutric acid in the treatment of alcohol dependence: a double-blind study. Alcohol Clin Exp Res 1992; 16: 673–6

    Article  PubMed  CAS  Google Scholar 

  18. Addolorato G, Caputo F, Capristo E, et al. Ability of baclofen in reducing alcohol craving and intake: II. Preliminary clinical evidence. Alcohol Clin Exp Res 2000; 24: 67–71

    CAS  Google Scholar 

  19. Flannery BA, Garbutt JC, Cody MW, et al. Baclofen for alcohol dependence: a preliminary open-label study. Alcohol Clin Exp Res 2004; 28: 1517–23

    Article  PubMed  CAS  Google Scholar 

  20. Addolorato G, Caputo F, Capristo E, et al. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol 2002; 37: 504–8

    Article  PubMed  CAS  Google Scholar 

  21. Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomized, double-blind controlled study. Lancet 2007; 370: 1915–22

    Article  PubMed  CAS  Google Scholar 

  22. Garbutt JC, Kampov-Polevoy AB, Gallop R, et al. Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res 2010; 34: 1–9

    Article  Google Scholar 

  23. Addolorato G, Leggio L, Ferrulli A, et al. Dose-response effect of baclofen in reducing daily alcohol intake in alcohol dependence: secondary analysis of a randomized, double-blind, placebo-controlled trial. Alcohol Alcohol 2011; 46: 312–7

    Article  PubMed  CAS  Google Scholar 

  24. Colombo G, Addolorato G, Agabio R, et al. Role of GABAB receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics. Neurotox Res 2004; 6: 403–14

    Article  PubMed  Google Scholar 

  25. Addolorato G, Leggio L, Cardone S, et al. Role of the GABAB receptor system in alcoholism and stress: focus on clinical studies and treatment perspectives. Alcohol 2009; 43: 559–63

    Article  PubMed  CAS  Google Scholar 

  26. Krystal JH, Tabakoff B. Ethanol abuse, dependence, and withdrawal: neurobiology and clinical implications. In: Davis KL, Charney D, Coyle JT, et al., editors. Neuropsychopharmacology: 5th generation of progress. New York (NY): Lippincott Williams and Wilkins; 2002: 1425–43

    Google Scholar 

  27. Sinha R, Fox HC, Hong KA, et al. Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals. Neuropsychopharmacology 2009; 34: 1198–208

    Article  PubMed  CAS  Google Scholar 

  28. Sinha R, Li CS. Imaging stress- and cue-inducing and alcohol craving: association with relapse and clinical implications. Drug Alcohol Rev 2007; 26: 25–31

    Article  PubMed  Google Scholar 

  29. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000

    Google Scholar 

  30. Jadad AR, Moore RA, Carrol D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin Trials 1996; 17: 1–12

    Article  PubMed  CAS  Google Scholar 

  31. Starosta AN, Leeman RF, Volpicelli JR. The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders. J Psychiatr Pract 2006; 2: 80–9

    Article  Google Scholar 

  32. Ameisen O. Complete and prolonged suppression of symptoms and consequences of alcohol-dependence using high-dose baclofen: a self-case report of a physician. Alcohol Alcohol 2005; 40: 147–50

    Article  PubMed  CAS  Google Scholar 

  33. Bucknam W. Suppression of symptoms of alcohol dependence and craving using high-dose baclofen. Alcohol Alcohol 2007; 42: 158–60

    Article  PubMed  CAS  Google Scholar 

  34. Agabio R, Marras P, Addolorato G, et al. Baclofen suppresses alcohol intake and craving for alcohol in a schizophrenic alcohol-dependent patient: a case report. J Clin Psychopharm 2007; 27: 319–20

    Article  Google Scholar 

  35. Gerkin R, Curry SC, Vance MV, et al. First-order elimination kinetics following baclofen overdose. Ann Emerg Med 1986; 15: 843–6

    Article  PubMed  CAS  Google Scholar 

  36. VanDierendonk DR, Dire DJ. Baclofen and ethanol ingestion: a case report. J Emerg Med 1999; 17: 989–93

    Article  PubMed  CAS  Google Scholar 

  37. Chen KS, Bullard MJ, Chien YY, et al. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997; 31: 1315–20

    PubMed  CAS  Google Scholar 

  38. Vivitrol® [package insert]. Waltharn (MA): Alkermes, Inc., 2010

  39. Amini M, Runyon BA. Alcoholic hepatitis 2010: a clinician’s guide to diagnosis and therapy. World J Gastroenterol 2010; 16: 4905–12

    Article  PubMed  Google Scholar 

  40. Evans SM, Bisaga A. Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcohol Clin Exp Res 2009; 33: 19–30

    Article  PubMed  CAS  Google Scholar 

  41. Addolorato G, Leggio L. Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. Curr Pharm Des 2010; 16: 2113–7

    Article  PubMed  CAS  Google Scholar 

  42. Krupitsky EM, Burakov AM, Ivanov VB, et al. Baclofen administration for the treatment of affective disorders in alcoholic patients. Drug Alcohol Depend 1993; 33: 157–63

    Article  PubMed  CAS  Google Scholar 

  43. Franklin TR, Harper D, Kampman K, et al. The GABA B agonist baclofen reduces cigarette consumptions in a preliminary double-blind placebo-controlled smoking reduction study. Drug Alcohol Depend 2009; 103: 30–6

    Article  PubMed  CAS  Google Scholar 

  44. Karilla L, Gorelick D, Weinstein A, et al. New treatment for cocaine dependence: a focused review. Int J Neuropsychopharmacol 2008; 11: 425–38

    Google Scholar 

  45. Keena GA, Nielsen DM, Mello P, et al. Pharmacotherapy of dual substance abuse and dependence. CNS Drugs 2007; 21:213–37

    Article  Google Scholar 

  46. Heinzerlin KG, Shoptaw S, Peck JA, et al. Randomized, placebo-controlled trial of baclofen and gabapentin for the treatment of methamphetamine dependence. Drug Alcohol Depend 2006; 85: 177–84

    Article  Google Scholar 

  47. Rose ME, Grant JE. Pharmacotherapy for methamphetamine dependence: a review of the pathophysiology of methamphetamine addiction and the theoretical basis and efficacy of pharmacotherapeutic interventions. Ann Clin Psychiatry 2008; 20: 145–55

    Article  PubMed  Google Scholar 

  48. US National Institutes of Health. ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Apr 25]

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Acknowledgements

No financial support was received for this publication. The authors of this paper have no sources of financial support or any conflicts of interest relevant to this publication. This paper (in part or in whole) has not been previously presented or published.

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Authors and Affiliations

  1. Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, P.O. Box 3089-Pharmacy, Durham, Buies Creek, NC, 27710, USA

    Andrew J. Muzyk Pharm.D., Assistant Professor

  2. Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA

    Andrew J. Muzyk Pharm.D., Assistant Professor, Sarah K. Rivelli & Jane P. Gagliardi

  3. Department of Medicine, Duke University, Durham, NC, USA

    Sarah K. Rivelli & Jane P. Gagliardi

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  1. Andrew J. Muzyk Pharm.D., Assistant Professor
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  2. Sarah K. Rivelli
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Correspondence to Andrew J. Muzyk Pharm.D., Assistant Professor.

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Muzyk, A.J., Rivelli, S.K. & Gagliardi, J.P. Defining the Role of Baclofen for the Treatment of Alcohol Dependence. CNS Drugs 26, 69–78 (2012). https://doi.org/10.2165/11597320-000000000-00000

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