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Pharmacological Long-Term Treatment of Alcohol Use Disorders

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Textbook of Addiction Treatment: International Perspectives

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Abstract

The acute and long-term consequences of alcohol use disorders are very well known. Multiple treatments for these disorders have been investigated, and some of them have received approval by regulatory agencies. Disulfiram blocks the natural degradation of alcohol. It inhibits the acetaldehyde dehydrogenase, and the accumulation of acetaldehyde in the body results in unpleasant symptoms such as rush, nausea, headache, diarrhea, vomiting, and a drop in blood pressure. Disulfiram should only be prescribed once the patient has been detoxified and is free of alcohol and without withdrawal symptoms. Naltrexone is a competitive opiate antagonist with high affinity to the μ-receptor and lower affinity to the δ- and κ-receptors and is approved to treat alcohol dependence in individuals who are not opioid dependent. Acamprosate binds to NMDA receptors and thus dampens the glutamate-mediated excitability and is approved for the treatment of alcohol dependence in people who already established a state of alcohol abstinence. Nalmefene is the most recent medication approved for use in alcohol dependence. It was approved by the European Medicines Agency in 2012 for a reduction of heavy drinking days and/or total alcohol consumption. Nalmefene is a selective opioid ligand with an equally high affinity to the μ- and κ-receptors and medium affinity to the δ-receptor. It acts as an antagonist at the μ- and δ-receptor, but different from naltrexone, it is a co-agonist at the κ-receptor. The official indication for nalmefene is to reduce alcohol consumption. The chapter will discuss these and other medications that are being investigated for the treatment of alcohol use disorders.

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References

  • Addolorato G, Caputo F, Capristo E et al (2002) Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol 37:504–508

    Article  CAS  PubMed  Google Scholar 

  • Addolorato G, Leggio L, Ferrulli A et al (2007) Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: a randomized, double-blind, controlled study. Lancet 370(9603):1915–1922

    Article  CAS  PubMed  Google Scholar 

  • Addorolato G, Leggio L (2010) Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. Curr Pharm Des 16(19):2113–2117

    Article  Google Scholar 

  • Agosti V (1995) The efficacy of treatments in reducing alcohol consumption: a meta-analysis. Int J Addict 30:1067–1077

    CAS  PubMed  Google Scholar 

  • Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by naltrexone. Life Sci 26:679–688

    Article  CAS  PubMed  Google Scholar 

  • Anton RF (2008) Genetic basis for predicting response to naltrexone in the treatment of alcohol dependence. Pharmacogenomics 9(6):655–658

    Article  CAS  PubMed  Google Scholar 

  • Anton RF, Pettinati H, Zweben A, Kranzler HR, Johnson B, Bohn MJ, McCaul ME, Anthenelli R, Salloum I, Galloway G, Garbutt J, Swift R, Gastfriend D, Kallio A, Karhuvaara S (2004) A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 24:421–428

    Article  CAS  PubMed  Google Scholar 

  • Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A, COMBINE Study Research Group (2006) Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 295:2003–2017

    Article  CAS  PubMed  Google Scholar 

  • Arbaizar B, Diersen-Sotos T, Gómez-Acebo I, Llorca J (2010) Topiramate in the treatment of alcohol dependence: a meta-analysis. Actas Esp Psiquiatr 38:8–12

    CAS  PubMed  Google Scholar 

  • Aubin HJ, Daeppen JB (2013) Emerging pharmacotherapies for alcohol dependence: a systematic review focusing on reduction in consumption. Drug Alcohol Depend. doi:pii: S0376-8716(13)00154-3. 10.1016/j.drugalcdep. Epub ahead of print

    Google Scholar 

  • Bart G, Schluger JH, Borg L, Ho A, Bidlack JM, Kreek MJ (2005) Nalmefene induced elevation in serum prolactin in normal human volunteers: partial kappa opioid agonist activity? Neuropsychopharmacology 30:2254–2262

    Article  CAS  PubMed  Google Scholar 

  • Berglund M, Thelander S, Salaspuro M, Franck J, Andréasson S, Ojehagen A (2003) Treatment of alcohol abuse: an evidence-based review. Alcohol Clin Exp Res 27:1645–1656

    Article  PubMed  Google Scholar 

  • Besson J, Aeby F, Kasas A, Lehert P, Potgieter A (1998) Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study. Alcohol Clin Exp Res 22:573–579

    Article  CAS  PubMed  Google Scholar 

  • Brennan JL, Leung JG, Gagliardi JP, Rivelli SK, Muzyk AJ (2013) Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review. Clin Pharmacol 5:99–107

    PubMed Central  PubMed  Google Scholar 

  • Brewer C (1993) Long-term, high-dose disulfiram in the treatment of alcohol abuse. Br J Psychiatry 163:687–689

    Article  CAS  PubMed  Google Scholar 

  • Brüeck G, Mann K (2006) Alkoholismusspezifische Psychotherapie: Manual mit Behandlungs-smodulen. (Alcoholism-specific psychotherapy: manual with treatment modules). Deutscher Ärzteverlag, Köln

    Google Scholar 

  • Chick J (1999) Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug Saf 20:427–435, Review

    Article  CAS  PubMed  Google Scholar 

  • Cowen MS, Adams C, Kraehenbuehl T, Vengeliene V, Lawrence AJ (2005) The acute anti-craving effect of acamprosate in alcohol-preferring rats is associated with modulation of the mesolimbic dopamine system. Addict Biol 10:233–242

    Article  CAS  PubMed  Google Scholar 

  • De Sousa A (2004) A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of alcohol dependence. Alcohol Alcohol 39:528–531

    Article  PubMed  Google Scholar 

  • Edenberg HJ, Koller DL, Xuei X, Wetherill L, McClintick JN, Almasy L, Bierut LJ, Bucholz KK, Goate A, Aliev F, Dick D, Hesselbrock V, Hinrichs A, Kramer J, Kuperman S, Nurnberger JI Jr, Rice JP, Schuckit MA, Taylor R, Todd Webb B, Tischfield JA, Porjesz B, Foroud T (2010) Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcohol Clin Exp Res 34:840–852

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Edwards G (2000) Alcohol: the world’s favorite drug. St. Martin’s Press, New York, p 118

    Google Scholar 

  • Edwards G (2005) History of prevention of relapse. In: Spanagel R, Mann K (eds) Drugs for relapse prevention of alcoholism. Birkhäuser Verlag, Switzerland

    Google Scholar 

  • Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, James KE, Lacoursiere RB, Lee KK, Lowenstam I et al. (1986) Disulfiram treatment of alcoholism. A Veterans Administration Cooperative Study. JAMA 256:1449–1455

    Article  CAS  PubMed  Google Scholar 

  • Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA (2010) Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res 34:1–9

    Article  Google Scholar 

  • Gastpar M, Bonnet U, Böning J, Mann K, Schmidt LG, Soyka M, Wetterling T, Kielstein V, Labriola D, Croop R (2002) Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German Multicenter Study. J Clin Psychopharmacol 22:592–598

    Article  CAS  PubMed  Google Scholar 

  • Gelernter J, Gueorguieva R, Kranzler HR, Zhang H, Cramer J, Rosenheck R, Krystal JH, VA Cooperative Study #425 Study Group (2007) Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study. Alcohol Clin Exp Res 31(4):555–563

    CAS  PubMed  Google Scholar 

  • Gianoulakis C, de Waele JP, Thavundayil J (1996) Implication of the endogenous opioid system in excessive ethanol consumption. Alcohol 13:19–23

    Article  CAS  PubMed  Google Scholar 

  • Gual A, He Y, Torup L, van den Brink W, Mann K, for the ESENSE 2 Study Group (2013) A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol. doi:pii: S0924-977X(13)00075-8. 10.1016/j. Epub ahead of print

    Google Scholar 

  • Harris BR, Prendergast MA, Gobson DA, Rogers DT, Blanchard JA, Holley RC, Fu MC, Hart SR, Pedigo NW, Littleton JM (2002) Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors. Alcohol Clin Exp Res 26:1779–1793

    Article  CAS  PubMed  Google Scholar 

  • Heilig M, Goldman D, Berrettini W, O’Brien CP (2011) Pharmacogenetic approaches to the treatment of alcohol addiction. Nat Rev Neurosci 12:670–684

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson BA (2005) Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs 19:873–896, Review

    Article  CAS  PubMed  Google Scholar 

  • Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ (2003) Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 361:1677–1685

    Article  CAS  PubMed  Google Scholar 

  • Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O’Malley SS, Swift RM (2007) Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 298:1641–1651

    Article  CAS  PubMed  Google Scholar 

  • Karhuvaara S, Simojoki K, Virta A, Rosberg M, Löyttyniemi E, Nurminen T, Kallio A, Mäkelä R (2007) Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study. Alcohol Clin Exp Res 31:1179–1187

    Article  CAS  PubMed  Google Scholar 

  • Kiefer F, Mann K (2010) Acamprosate: how, where, and for whom does it work? Curr Pharm Des 16(19):2098–2102

    Article  CAS  PubMed  Google Scholar 

  • Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R, Kämpf P, Stracke R, Baehr M, Naber D, Wiedemann K (2003) Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 60:92–99

    Article  CAS  PubMed  Google Scholar 

  • Kiefer F, Witt SH, Frank J, Richter A, Treutlein J, Lemenager T, Nöthen MM, Cichon S, Batra A, Berner M, Wodarz N, Zimmermann US, Spanagel R, Wiedemann K, Smolka MN, Heinz A, Rietschel M, Mann K (2011) Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate. Pharmacogenomics J 11:368–374

    Article  CAS  PubMed  Google Scholar 

  • Krampe H, Stawicki S, Wagner T, Bartels C, Aust C, Rüther E, Poser W, Ehrenreich H (2006) Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome. Alcohol Clin Exp Res 30:86–95

    Article  PubMed  Google Scholar 

  • Krystal JH, Cramer JA, Krol WF, Kirk GF, Rosenheck RA (2001) Naltrexone in the treatment of alcohol dependence; Veterans Affairs Naltrexone Cooperative Study 425 Group. N Engl J Med 345:1734–1749

    Article  CAS  PubMed  Google Scholar 

  • Laaksonen E, Koski-Jännes A, Salaspuro M, Ahtinen H, Alho H (2008) A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. Alcohol Alcohol 43:53–61

    Article  CAS  PubMed  Google Scholar 

  • Lee MC, Wagner HN Jr, Tanada S, Frost JJ, Bice AN, Dannals RF (1988) Duration of occupancy of opiate receptors by naltrexone. J Nucl Med 29:1207–1211

    CAS  PubMed  Google Scholar 

  • Lewin L (1931) Phantastica: narcotic and stimulating drugs. Kegan Paul/Trench and Trubner, London

    Google Scholar 

  • Lhuintre JP, Daoust M, Moore ND, Chretien P, Saligaut C, Tran G, Bosimare F, Hillemand B (1985) Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics. Lancet 1:1014–1016

    Article  CAS  PubMed  Google Scholar 

  • Likhitsathian S, Uttawichai K, Booncharoen H, Wittayanookulluk A, Angkurawaranon C, Srisurapanont M (2013) Topiramate treatment for alcoholic outpatients recently receiving residential treatment programs: a 12-week, randomized, placebo-controlled trial. Drug Alcohol Depend. doi:pii: S0376-8716(13)00251-2. Epub ahead of print

    Google Scholar 

  • Mann K (2004) Pharmacotherapy of alcohol dependence: a review of the clinical data. CNS Drugs 18:485–504

    Article  CAS  PubMed  Google Scholar 

  • Mann K, Lehert P, Morgan MY (2004) The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp Res 28:51–63

    Article  PubMed  Google Scholar 

  • Mann K, Kiefer F, Spanagel R, Littleton JM (2008) Acamprosate: recent findings and future research directions. Alcohol Clin Exp Res 32:1105–1110

    Article  CAS  PubMed  Google Scholar 

  • Mann K, Kiefer F, Smolka M, Gann H, Wellek S, Heinz A (2009) Searching for responders to acamprosate and naltrexone in alcoholism treatment: rationale and design of the PREDICT study. Alcohol Clin Exp Res 33:674–683

    Article  CAS  PubMed  Google Scholar 

  • Mann K, Bladström A, Torup L, Gual A, van den Brink W, The ESENSE 1 Study Group (2013) Extending the treatment options for patients with alcohol dependence – a randomised controlled study of nalmefene. Biol Psychiatry 73:706–713

    Article  CAS  PubMed  Google Scholar 

  • Marie C (1955) A propos d’un nouveau mode de traitement de l’alcoolisme chronique par implantation de disulfure de tétraéthylthiourame. (A new way of treating chronic alcoholism by implanting tetraethylthiuran disulfat) Thèse, Paris

    Google Scholar 

  • Martensen-Larsen O (1948) Treatment of alcoholism with a sensitizing drug. Lancet 25:6539

    Google Scholar 

  • Mason BJ, Salvato FR, Williams LD, Ritvo EC, Cutler RB (1999) A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry 56:719–724

    Article  CAS  PubMed  Google Scholar 

  • Morley KC, Teesson M, Reid SC, Sannibale C, Thomson C, Phung N, Weltman M, Bell JR, Richardson K, Haber PS (2006) Naltrexone versus acamprosate in the treatment of alcohol dependence: a multi-centre, randomized, double-blind, placebo-controlled trial. Addiction 101:1451–1462

    Article  PubMed  Google Scholar 

  • O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 49:881–887

    Article  PubMed  Google Scholar 

  • Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O’Brien CP (2003) A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 28:1546–1552

    Article  CAS  PubMed  Google Scholar 

  • Pettinati HM, Weiss RD, Miller WR, Donovan D, Ernst DB, Rounsaville BJ (2004) volume 2. Medical management treatment manual: a clinical research guide for medically trained clinicians providing pharmacotherapy as part of the treatment for alcohol dependence. DHHS publication no. (NIH) 04-5289. NIAAA, Bethesda

    Google Scholar 

  • Pierrefiche O, Daoust M, Naassila M (2004) Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network. Neuropharmacology 47:35–45

    Article  CAS  PubMed  Google Scholar 

  • Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M (2010a) Acamprosate for alcohol dependence. Cochrane Database Syst Rev 9, CD004332

    PubMed  Google Scholar 

  • Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M (2010b) Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 12:CD001867

    PubMed  Google Scholar 

  • Sinclair JD, Alho H, Shinderman M (2002) Naltrexone for alcohol dependence. N Engl J Med 346:1329–1331

    PubMed  Google Scholar 

  • Spanagel R, Kiefer F (2008) Drugs for relapse prevention of alcoholism: ten years of progress. Trends Pharmacol Sci 29(3):109–115

    Article  CAS  PubMed  Google Scholar 

  • Spanagel R, Mann K (eds) (2005) Drugs for relapse prevention in alcoholism. Birkhäuser Verlag, Basel

    Google Scholar 

  • Spanagel R, Zieglgänsberger W (1997) Anti-craving compounds for ethanol: new pharmacological tools to study addictive processes. Trends Pharmacol Sci 18:54–59

    Article  CAS  PubMed  Google Scholar 

  • Starosta AN, Leeman RF, Volpicelli JR (2006) The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders. J Psychiatr Pract 12:80–89

    Article  PubMed Central  PubMed  Google Scholar 

  • Treutlein J, Cichon S, Ridinger M, Wodarz N, Soyka M, Zill P, Maier W, Moessner R, Gaebel W, Dahmen N, Fehr C, Scherbaum N, Steffens M, Ludwig KU, Frank J, Wichmann HE, Schreiber S, Dragano N, Sommer WH, Leonardi-Essmann F, Lourdusamy A, Gebicke-Haerter P, Wienker TF, Sullivan PF, Nöthen MM, Kiefer F, Spanagel R, Mann K, Rietschel M (2009) Genome-wide association study of alcohol dependence. Arch Gen Psychiatry 66:773–784

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • van den Brink W, Aubin HJ, Bladström A, Torup L, Gual A, Mann K (2013) Efficacy of nalmefene as-needed in alcohol dependent patients with at least high drinking risk level: results from a subgroup analysis of two randomised controlled 6-month studies. Alcohol & Alcohol, ahead of print

    Google Scholar 

  • Verheul R, van den Brink W, Geerlings P (1999) A three-pathway psychobiological model of craving for alcohol. Alcohol Alcohol 34:197–222

    Article  CAS  PubMed  Google Scholar 

  • Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880

    Article  CAS  PubMed  Google Scholar 

  • Walker BM, Zorrilla EP, Koob GF (2011) Systemic κ-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addict Biol 16:116–119

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH (2004) Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia 41(Suppl 1):S17–S20

    Google Scholar 

  • Witte P, Bachteler D, Spanagel R (2005) Acomprasate: preclinical data. In: Spanagel and Mann (eds) Drugs for Relapse Prevention of Alcoholism. Birkhäuser Verlag, Basel, Boston, Berlin, 2005:73–84

    Google Scholar 

  • World Health Organization (WHO) (2000) International guide for monitoring alcohol consumption and related harm. WHO/MSD/MSB/00.4. 2000 http://whqlibdoc.who.int/hq/2000/who_msd_msb_00.4.pdf

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  1. Central Institute of Mental Health, Mannheim, Germany

    Karl Mann & Falk Kiefer

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  1. Karl Mann
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  2. Falk Kiefer
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Correspondence to Karl Mann .

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Editors and Affiliations

  1. Department of Psychiatry, Alberta Gambling Research Institute University of Calgary, Calgary, Alberta, Canada

    Nady el-Guebaly

  2. Faculty of Brain Sciences UCL Division of Psychiatry, University College London, London, United Kingdom

    Giuseppe Carrà

  3. Division of Alcoholism & Drug Abuse, New York University School of Medicine, New York, New York, USA

    Marc Galanter

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Mann, K., Kiefer, F. (2015). Pharmacological Long-Term Treatment of Alcohol Use Disorders. In: el-Guebaly, N., Carrà, G., Galanter, M. (eds) Textbook of Addiction Treatment: International Perspectives. Springer, Milano. https://doi.org/10.1007/978-88-470-5322-9_12

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