Nervenheilkunde 2021; 40(08): 628-635
DOI: 10.1055/a-1513-9420
Schwerpunkt

Pharmakologische Rückfallprophylaxe der Alkoholabhängigkeit

Pharmacotherapy of alcohol use disorders
Michael Soyka
1   Psychiatrische Universitätsklinik LMU München
› Author Affiliations

ZUSAMMENFASSUNG

Nur wenige Substanzen sind als sogenannte Anti-Craving-Me-dikamente zur pharmakogestützten Rückfallprophylaxe der Alkoholabhängigkeit zugelassen. Dazu gehören das in Deutschland nicht mehr vertriebene Disulfiram, die Opioidantagonisten Naltrexon und Nalmefen sowie Acamprosat. Gerade für Acamprosat und Naltrexon ist die Evidenzbasierung recht gut, bei mäßiger, aber klinisch signifikanter Effizienz. Sie werden trotzdem selten eingesetzt. Interessante Substanzen mit klinischer Perspektive sind am ehesten Baclofen, Vareniclin und Gabapentin. Die klinischen Befunde und Perspektiven der Pharmakotherapie bei Alkoholabhängigkeit werden dargestellt.

ABSTRACT

Few medications are approved for treatment of alcohol dependence, including acamprosate, naltrexone und nalmefene. Disulfiram is not marketed anymore in Germany. Acamprosat and naltrexone have a good evidence for efficacy, with modest clinical efficacy. They are rarely used. Emerging drugs of interest are baclofen, vareniclin, gabapentin, among others. Clinical perspectives of pharmacotherapy of alcoholism are discussed.



Publication History

Article published online:
04 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Soyka M, Batra A, Heinz A. et al (Hrsg.) Suchtmedizin. München: Elsevier. 2019.
  • 2 Kranzler HR, Soyka M. Diagnosis and Pharmacothearpy of Alcohol Use Disorder. A Review. JAMA 2018; 320: 815-826
  • 3 World Health Organization (WHO). International Guide for Monitoring Alcohol Consumption and related Harm. Geneva: World Health Organization. 2000
  • 4 World Health organization (WHO). Global Status Report on Alohol and Health. 2018. Geneva: WHO;
  • 5 Kendler KS, Ohlsson H, Sundquist J. et al Alcohol use Disorder and mortality across the lifespan: a longitudinal cohort and co-relative analysis. Am J Psychiatry 2017; 73: 575-581
  • 6 Rehm J, Dawson D, Frick U. et al Burden of disease associated with alcohol use disorders in the United States. Alcohol Clin Exp Res 2014; 38 (04) 1068-77
  • 7 Schuckit M. Alcohol use disorders. Lancet 2009; 373: 492-501
  • 8 Edwards G, Brown D, Oppenheimer E. et al Long term outcome for patients with drinking problems: the search for predictors. Br J Addict 1988; 83: 917-927
  • 9 Marshall EJ, Edwards G, Taylor C. Mortality in men with drinking problems: a 20-year follow-up. Addiction 1994; 89: 1293-1298
  • 10 National Institute for Health and Care Excellence. Alcohol Use Disorders: Diagnosis Assessment and Management of Harmful Drinking and Alcohol Dependence. London: National Institute for Health and Care Excellence; 2011
  • 11 Mann K, Hoch E, Batra A. (Hrsg.). S3-Leitlinie Screening Diagnose und Behandlung alkoholbezogener Störungen. Heidelberg: Springer; 2016
  • 12 Miller WR. Wilbourne. Mesa Grande: A methodological analysis of clinical trials of treatments for alcohol use disorders Addiction. 2002. 27. 867-886
  • 13 McGrady BS, Owens MD, Borders AZ. et al Psychosocial approaches to alcohol use disorders since 1040: A review. J Stud Alcohol Drugs 2014; 68-78
  • 14 Soyka M, Rösner S. Pharmakotherapie der Alkoholentwöhnung: Update und neue Entwicklungen Nervenarzt. 2021; 92: 57-65
  • 15 AWMF. Screening Diagnose und Behandlung alkoholbezogener Störungen. AWMF-Register 076-001. 2021
  • 16 Stevenson M, Pandor A, Stevens JW. et al Nalmefene for reducing alcohol consumption in people with alcohol dependence: an evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics 2015; 33: 833-847
  • 17 Fitzgerald N, Angus K, Elders A. et al Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers. Addiction 2016; 111: 14477-1487
  • 18 Naudet F, Palpaceur V, Boussageon R. et al Evaluation in alcohol use disorders - insights from the nalmefene experience. BMC Med 2016; 14: 119-127
  • 19 Witkiewitz K, Heather N, Falk DE. et al World health Organization risk drinking level reductions are associated with improved functioning and are sustained among patients with mild moedrate and severe al- cohol dependence in clinical trails in the United states and the United Kingdom. Addiction 2020; 115: 1668-1680
  • 20 Heinz A, Mascarell-Maricic L, Liu S. et al Die Imagen-Kohorte: Perspektiven und Probleme longitudinaler Forschung. Nervenarzt 2021; 92: 228-233
  • 21 Witkiewitz K, Litten RZ, Leggio L. Advances in the science and treat- ment of alcohol use disorder. Sci Adv 2019; 5
  • 22 Goh ET, Morgan MY. Review Article: Pharmacotherapy for alcohol dependence - the why the what and the wherefore. Aliment Pharmacol 2017; 45: 865-882
  • 23 Donoghue K, Elzerbi C, Saunders R. et al The efficacy of acamprosa- te and naltrexone in the treatment of alcohol dependence Europe versus the rest of the world: a meta-analysis. Addiction 2015; 110 (06) 920-30
  • 24 Shen WW. Anticraving therapy for alcohol use disorder: A clinical review. Neuropsychopharmacol Rep 2018; 38 (03) 105-16
  • 25 Maisel NC, Blodgett JC, Wilbourne PL. et al Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?. Addiction 2013; 108 (02) 275-93
  • 26 Klemperer EM, Hughes JR, Naud S. Study characteristics influence the efficacy of substance abuse treatments: A meta-analysis of medications for alcohol use disorder. Drug Alcohol Depend 2018; 190: 229-234
  • 27 Rösner S, Soyka M. Outcome Assessment in Trials of Pharmacological Treatments for Alcohol Use Disorders. CNS Drugs 2019; 33: 649-657
  • 28 Allen JP. Measuring outcome in interventions for alcohol dependence and problem drinking: executive summary of a conference sponsored by the national institute on alcohol abuse and alcoholism. Alcohol Clin Exp Res 2003; 27 (010) 1657-60
  • 29 Hasin DS, Wall M, Witkiewitz K. et al Change in non-abstinent WHO Drinking Risk levels and Alcohol Dependence A 3 year Follow-up results in the US. General polulation. Alcohol Clin Exp Res 2018; 42: 2256-2265
  • 30 European Medicines Agency. Guideline on the development of medicinal products for the treatment of alcohol dependence. London: European Medicines Agency; 2010
  • 31 Palpacuer C, Duprez R, Huneau A. et al Pharmacologically control- led drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene naltrexone acamprosate baclofen and topiramate. Addiction 2018; 113 (02) 220-37
  • 32 Tiffany ST, Friedman L, Greenfield SF. et al Beyond drug use: a systematic consideration of other outcomes in evaluations of treatments for substance use disorders. Addiction 2012; 107 (04) 709-18
  • 33 Falk DE O'Malley SS, Witkiewitz K. et al Evaluation of drinking risk levels as outcomes in alcohol pharmacotherapy. JAMA Psychiatry 2019; 76: 374-381
  • 34 Rösner S, Grosshans M, Mutschler JH. Disulfiram: Aktuelle Befunde und Wirkmechanismen. Suchtmed 2014; 16 (02) 47-52
  • 35 Mutschler J, Grosshans M, Soyka M. et al Current Findings and Mecha- nisms of Action of Disulfiram in the Treatment of Alcohol Dependence. Pharmacopsychiatry 2016; 49 (04) 137-41
  • 36 Fuller RK, Branchey L, Brightwell DR. et al Disulfiram treatment of alcoholism: A Veterans Administration cooperative study. JAMA 1986; 1149-1455
  • 37 Skinner MD, Lahmek P, Pham H. et al Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis. PloS one 2014; 9 (02)
  • 38 Krampe H, Stawicki S, Hoehe MR. et al Outpatient Long-term Intensive for alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism. Dialogues Clin Neurosci 2007; 9: 399-412
  • 39 Spanagel R, Vengeliene V, Jandeleit B. et al Acamprosate Produces its Anti-Relapse Effects Via Clacium. Neuropsychopharmacology 2914 39: 783-791
  • 40 Jonas DE, Amick HR, Feltner C. et al Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA 2014; 311 (018) 1889-900
  • 41 Sinclair JM, Chambers SE, Shiles CJ. et al Safety and tolerability of pharmacological treatment of alcohol dependence: comprehensive review of evidence. Drug Saf 2016; 39: 981-993
  • 42 Cheng H-Y, McGuinness LA, Elbers RG. et al Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis. BMJ 2020; 371-m3934 DOI: 10.1136/bmj.m3934.
  • 43 Rosner S, Hackl-Herrwerth A, Leucht S. et al Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010; (09) CD004332
  • 44 Anton RF O'Malley SS, Ciraulo DA. Combined pharmacotherapies and behavioural interventions for alcohol dependence; the Combine study: a randomized controlled trial. JAMA 2006; 295: 2003-2017
  • 45 Kiefer J, Jahn H, Tarnaske T. et al Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind placebo-controlled study. Arch Gen Psychiatry 2003; 60: 92-99
  • 46 Hansson AC, Gründer G, Hirth A. et al Dopamine and opioid systems adaptation in alcoholism revisited: Convergent evidence from positron emission tomography and postmortem studies. Neuroscience Biobehav Rev 2019; DOI: 10.1016/j.neubiorev.2018.09.010.
  • 47 Ray LA, Green RJ, Roche DJO. et al Naltrexone Effects on Subjective Responses to Alcohol in the Human Laboratory: A Systematic Review and Meta-Analysis. Addict Biol 2019; 24: 1138-1152
  • 48 O'Malley SS, Jaffe AJ, Chang G. et al Naltrexone and coping skills the- rapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 1992; 49 (011) 881-7
  • 49 Volpicelli JR, Alterman M, Hayashida C. et al Naltrexone in the treatment of alcohol dependence. Arch Neurol 1992; 19: 603-617
  • 50 Bolton M, Hodkinson A, Boda S. et al Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. BMC Med 2019; 17: 10
  • 51 Gual A, He Y, Torup L. et al A randomized double-blind placebo-con- trolled efficacy study of nalmefene as-needed use in patients with alcohol dependence. Eur Neuropsychopharmacol 2013; 23: 1432-1442
  • 52 Mann K, Bladström A, Torup L. et al Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013; 73: 706-713
  • 53 Van den Brink W, Sorensen P, Torup L. et al Long-term efficacy tolerability and safety of nalmefene as-needed in patients with alcohol dependence: a 1-year randomized controlled study. J Psychopharma- col 2014; 28: 733-744
  • 54 Van den Brink W, Aubin HJ, Bladström A. et al Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies. Alcohol Alcohol 2013; 48: 570-578
  • 55 Palpacuer C, Laviolle B, Boussageon R. et al Risks and benefits of nalmefene in the treatment of adult alcohol dependence: a systematic literature review and meta-analysis of published and unpub- lished double-blind randomized controlled trials. Plos Med 2015; 12: e1001924
  • 56 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: 147-150
  • 57 Addolorato G, Caputo F, Capristo E. et al Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind study randomi- zed controlled study. Alcohol Alcohol 2002; 37: 123-135
  • 58 Addolorato G, Leggio L, Ferulli 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: 1915-1922
  • 59 Addolorato G, Leggio L, Ferrulliu 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: 312-317
  • 60 Garbutt JC, Kampov-Polevoy AB, Gallop P. et al Efficacy and safety of baclofen for alcohol dependence: a randomized double-blind placebo-controlled trial. Alcohol Clin Exp Res 2010; 34: 1849-1857
  • 61 Ponizovsky AM, Rosca P, Aronovich E. et al Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a randomized double-blind placebo controlled trial with 1 year follow-up. J Subst Abuse treat 2015; 52: 24-30
  • 62 Morley KC, Baillie A, Leung S. et al Baclofen for the treatment of alcohol dependence and possible role of comorbid anxiety. Alcohol Alcohol 2014; 49: 654-660
  • 63 Behara EM, Salemink E, Goudriaan AE. et al Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: a multicenter randomized double-blind controlled trial. Eur Neuropsychopharmacol 2016; 1950-1959
  • 64 Müller CA, Geisel O, Pelz P. et al High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized placebo-cont- rolled trial. Eur Neuropsychopharmacol 2015; 25: 1167-1177
  • 65 Rolland B, Labreuche J, Duhamel A. et al Baclofen for alcohol dependence: relationships between baclofen and alcohol dosing and the occurrence of major sedation. Eur Neuropsychopharmaol 2015; 25: 1631-1636
  • 66 Chaignot C, Zureik M, Rey G. et al Risk of hospitalization and death related to baclofen for alcohol use disorders: Comparison with nalmefene acamprosate and naltrexone in a cohort study of 165334 patients between 2009 and 2015 in France. Pharmacoepidemiol Drug Saf 2016; 27: 1239-1248
  • 67 Reynaud M, Aubin H-J, Trinquet F. et A Randomized Placebo-controlled Study of High-Dose Baclofen in Alcohol-Dependent Patients - the ALPADIR study. Alcohol Alcohol 2017; 52: 439-446
  • 68 Minozzi S, Saulle R, Rösner S. Baclofen for alcohol use disorder. Cochrane Database Syst Rev 2018; 11: CD012557
  • 69 Rose AK, Jones A. Baclofen: Its Effectiveness in reducing Harmful Drinking Craving and Negative Mood. A Meta-analysis Addiction 2018; 113: 1396-1406
  • 70 Andrade C. Individualized High-Dose Baclofen for Reduction in Alcohol Intake in Persons with high levels of Consumption. J Clin Psychiatry 2020; 81: 20-f13606
  • 71 Sills GJ. The mechanisms of action of gabapentin and pregabalin. Opin Pharmacol 2006; 6: 108-113
  • 72 Kranzler HR, Feinn R, Morris P. et al A Meta-analysis of the Efficacy of Gabapentin for Treating Alcohol Use Disorder. Addiction 2019; 114: 1547-1555
  • 73 Ahmed S, Stanciu CN, Kotapati PV. et al Effectiveness of Gabapentin in Reducing Cravings and Withdrawal in Alcohol Use Disorder: A Me- ta-analytic Review. Prim Care Companion CNS Disord 2019; 21-4
  • 74 Vickers-Smith R, Sun J, Charnigo RJ. et al Gabapentin Drug Misuse Signals: A Pharmacovigilance Assessment using the FDA Adverse Event Reporting System. Drug Alcohol Depend. 2019; doi.1010.16/j.drugalcdep.2019.107709.
  • 75 Andrade C. Gabapentin for alcohol-related disorders: critical apprai- sal of the symptom-driven approach. J Clin Psychiatry 2020; 81: 20-f13775
  • 76 Johnson BA, Ait-Daoud N, Bowden CL. et al Oral topiramate for tre- atment of alcohol dependence: a randomized controlled trial. Lancet 2003; 361: 1677-1685
  • 77 Johnson BA, Rosenthal N, Capece JA. et al Topiramate for treating alcohol dependence: A randomized controlled trial. JAMA 2007; 198: 1641-1651
  • 78 Blodgett JC, Del Re AC, Maisel NC. et al A meta-analysis of topirama- te's effects for individuals with alcohol use disorders. Clin Exp Res 2014; 38: 1481-1488
  • 79 Pani PP, Trogu E, Pacini M. et al Anticonvulsants for alcohol dependen- ce. Cochrane Database Syst Rev 2014; 2: Cd008544
  • 80 Leggio L, Falk DE, Ryan ML. et al Medication Development for Alcohol Use Disorder: A Focus on Clinical Studies In: Nader MA Hurd YL (eds) Substance Use Disorders. Handbook of Experimental Pharamcology 2019; DOI: 10.1007/164_2019_295.
  • 81 Litten RZ, Ryan ML, Fertig JR. et al A double-blind placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med 2013; 7: 277-286
  • 82 De Bejczy A, Lof E, Walther L. et al Varenicline for treatment of alcohol dependence: a randomized placebo-controlled trial. Alcohol Clin Exp Res 2015; 39: 2189-2199
  • 83 Gandhi KD, Mansukhani MP, Karpyak VM. et al The Impact of Varenicline on Alcohol Consumption in Subjects with Alcohol Use Disorders: Systematic Review and Meta-Analyses. J Clin Psychiatry 2020; 81: 19-r12924
  • 84 Keating GM. Sodium Oxybate: A Review of Its Use in Alcohol With- drawal Syndrome and in the Maintenance of Abstinence in Alcohol Dependence. Clin Drug Invest 2014; 34: 63-80
  • 85 Van den Brink W, Addolorato G, Aubin H-J. et al Efficacy and Safety of Sodium Oxybate in Alcohol-Dependent Patients with a Very High Drinking Risk Level. Addict Biol 2018; 23: 969-986
  • 86 Zastrozhin MS, Skryabin VYU, Miroshkin SS. et al Pharmacogenetics of alcohol addiction: current perspectives. Appl Clin Genet 2019; 12: 131-140
  • 87 Hartwell EE, Kranzler HR. Pharmacogenetics of alcohol use disorder treatments: an update. Expert Opin Drug Metab Toxicaol 2019; 15: 553-564
  • 88 Fairbanks J, Umbreit A, Kolla BP. et al Evidence-based Pharmacothe- rapies for Alcohol Use Disorder: Clinical Pearls. Mayo Clin Proc 2020; 95: 1964-1977
  • 89 Knox J, Hasin DS, Larson FRR. et al Prevention screening and treatment for heavy drinking and alcohol use disorder. Lancet Psychiatry 2019; 6: 1054-1067
  • 90 Thompson A, Ashcroft DM, Owens L. et al Drug Therapy for alcohol dependence in primary care in the UK: a clinical practice research datalink study. Plos One 2017; 12: 1-14
  • 91 Heikinnen M, Taipale H, Tanskanen A. et al Real-world effectiveness of pharmacological treatments of alcohol use disorders in a Swedish nation-wide cohort of 125556 patients Addiction. 2021; DOI: 10.1111/add.15384.
  • 92 Huh SY, Kim S.G, Hong TK. Predictive factors of long-term follow-up in treatment of Korean alcoholics with naltrexone or acamprosate. Int Clin Psychopharmacol 2020; 35: 345-350
  • 93 Kenna GA, Zywiak WH, Swift RM. et al Ondansetron reduces naturali- stic drinking in nontreatment-seeking alcohol-dependent individuals with the LL 5'-HTTLPR genotype: a laboratory study. Alcohol Clin Exp Res 2014; 38: 1567-1574
  • 94 Johnson BA, Ait-Daoud C, Seneviratne J. et al Pharmacogenetic appro- ach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking. Am J Psychiatry 2011; 168: 265-275
  • 95 Haass-Koffler CL, Swift RM. Noradrenergic targets for the treatment of alcohol use disorder. Psychopharmacology 2018; 235: 1625-1634
  • 96 Simpson TL, Saxon AJ, Stappenbeck C. et al Double-blind randomized clinical trial of prazosin for alcohol use disorder. Am J Psychiatry 2018; 175: 1216
  • 97 Crowley NA, Magee SN, Feng M. et al Ketamine normalizes binge drinking-induced defects in glutamatergic synaptic transmission and ethanol drinking behavior in female but not malre rats. Neurophar- macology 2019; 149: 35-44
  • 98 Das RK, Gale G, Walsh K. et al Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories. Nature Communications 2019; 10: 5187
  • 99 Campbell EJ, Marchant NJ, Lawrencs AJ. A sleeping giant: Survorexant for the traetment of alcohol use disorder?. Brain Res 2020 1731; 145-902
  • 100 Fehr C, Coste F, Rahhali N. et al Die Behandlungswirklichkeit alkoholabhängiger Patienten in der täglichen medizinischen Praxis in Deutschland. Suchtmed 2015; 17: 233-246
  • 101 Agabio R, Trogu E, Pani PP. Antidepressants for the Treatment of Peo- ple with Co-Occuring Depression and Alcohol Dependence. Cochrane Database Syst Rev 2018; 4: CD008581
  • 102 Kishie T, Devy S, Chekuri R. et al Antipsychotics for Primary Alcohol Dependence: A Systematic Review and Meta-Analysis of Placebo-Con- trolled Trials. J Clin Psychiatry 2013; 74: 7