Acamprosat und Naltrexon als Kombinationstherapie bei Alkoholund Benzodiazepinabhängigkeit

Zusammenfassung

Acamprosat und Naltrexon sind etablierte Strategien zur pharmakologischen Rückfallprophylaxe bei Patienten mit Alkoholabhängigkeit. Obwohl die Kombination beider Substanzen bei dieser Indikation aufgrund pharmakodynamischer und -kinetischer Überlegungen eine sinnvolle Therapieoption darstellt, welche in klinischen Studien als effektiv und sicher beschrieben wurde, wird sie im klinischen Alltag selten eingesetzt. Wir berichten über eine erfolgreiche Behandlung von Acamprosat und Naltrexon bei einer Patientin mit einer schweren Alkohol-und Benzodiazepinabhängigkeit, welche unter dieser Therapie das längste Abstinenzintervall seit der Entwicklung ihrer Suchterkrankung erreichen konnte.

Summary

Acamprosate and naltrexone are established strategies for pharmacologic relapse prevention in patients with alcohol dependence. Regarding pharmacodynamic and -kinetic considerations the combination of both agents for this indication is a reasonable treatment option that has been described to be safe and effective in clinical studies. However, this combination is uncommon in clinical practice. We report the case of a patient with severe alcoholand benzodiazepine dependence who achieved her longest interval of abstinence under combined treatment with acamprosate and naltrexone since the development of her addiction.

Schlüsselwörter

Abhängigkeit - Abstinenz - Craving - Rückfallprophylaxe

Keywords

Addiction - abstinence - craving - relapse prevention

• Literatur

• 1 Koob G. Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 2003; 27: 232-243.
• 2 Mutschler J, Diehl A, Kiefer F. Pharmacology of disulfiram – an update. Fortschr Neurol Psychiatr 2008; 76: 225-241.
• 3 Krampe H, Stawicki S, Wagner T. et al. Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrants on outcome. Alcohol Clin Exp Res 2006; 30: 86-95.
• 4 Malcolm R, Olive M, Lechner W. The safety of disufiram for the treatment of alcohol and cocaine dependence in randomized clinical trials: guidance for clinical practice. Expert Opin Drug Saf 2008; 07: 459-472.
• 5 Pierrefiche O, Daoust M, Naassila M. Biphasic effect of acamprosate on NMDA but not on GABA A receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network. Neuropharmacology 2004; 47: 35-45.
• 6 Daoust M, Legrand E, Gewiss M. et al. Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats. Pharmacol Biochem Behav 1992; 41: 669-674.
• 7 Mann K, Kiefer F, Spanagel R, Littleton J. Acamprosate: recent findings and future research directions. Alcohol Clin Exp Res 2008; 32: 1105-1110.
• 8 Naassila M, Hammoumi S, Legrand E, Durbin P, Daoust M. Mechanism of action of acamprosate. Part I. Characterization of spermidine-senstitive acamprosate binding site in rat brain. Alcohol Clin Exp Res 1998; 22: 802-809.
• 9 Mason B, Heyser C. Acamprosate: a prototypic neuromodulator in the treatment of alcohol dependence. CNS Neurol Disord Drug Targets 2010; 09: 23-32.
• 10 Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010; Sep 8(9): CD004332.
• 11 Mason B, Heyser C. The neurobiology, clinical efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence. Expert Opin Drug Saf 2010; 09: 177-188.
• 12 Koob G, Roberts A, Schulteis G. et al. Neurocircuitry targets in ethanol reward and dependence. Alcohol Clin Exp Res 1998; 22: 3-9.
• 13 Hillemacher T, Heberlein A, Muschler M, Bleich S, Frieling H. Opioid modulators for alcohol dependence. Expert Opin Investig Drugs 2011; 20: 1073-1086.
• 14 Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010; 12: CD001867.
• 15 Pettinati H, Gastrfriend D, Dong Q, Kranzler H, O´Malley S. Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients. Alcohol Clin Exp Res 2009; 33: 350-356.
• 16 Lee J, Grossmann E, DiRocco D. et al. Extended-release naltrexone for treatment of alcohol dependence in primary care. J Subst Abuse Treat 2010; 39: 14-21.
• 17 Soyka M, Rösner S. Nalmefene for treatment of alcohol dependence. Expert Opin Investig Drugs 2010; 19: 1451-1459.
• 18 Ingman K, Hagelberg N, Aalto S. et al. Prolonged central mu-opioid receptor occupancy after single and repeated nalmefene dosing. Neuropsychopharmacology 2005; 30: 2245-2253.
• 19 Mason B, Salvato F, Williams L, Ritvo E, Cutler R. A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry 1999; 56: 719-724.
• 20 Emmerosn P, Liu M, Woods J, Medzihradsky F. Binding affinity and selectivity of opioids at mu, delta and kappa receptors in monkey brain membranes. J Pharmacol Exp Ther 1994; 271: 1630-1637.
• 21 Garbutt J, Kampov-Polevoy A, Gallop R, Kalka-Juhl L, Flannery B. Efficacy and safety of baclofen for alcohol dependence: a randomized, doubleblind, placebo-controlled trial. Alcohol Clin Exp Res 2010; 34: 1849-1857.
• 22 Cloninger C. Neurogenetic adaptive mechanisms in alcoholism. Science 1987; 236: 410-416.
• 23 Cooper J. ICD-10 Classification of Mental and Behavioural Disorders with Glossary and Diagnostic Criteria for Research ICD-10:DCR-10. Edinburgh, London, Melbourne, New York, Tokyo: WHO; 1994
• 24 Mason B, Goodman A, Dixon R. et al. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology 2002; 27: 596-606.
• 25 Johnson B, O´Malley S, Ciraulo D. et al. Doseranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J Clin Psychopharmacol 2003; 23: 281-293.
• 26 COMBINE Study Research Group. Testing combined pharmacotherapies and behavioral interventions for alcohol dependence (the COMBINE study): a pilot feasibility study. Alcohol Clin Exp Res 2003; 27: 1123-1131.
• 27 Kiefer F, Jahn H, Tarnaske T. et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism. Arch Gen Psychiatry 2003; 60: 92-99.
• 28 Feeney G, Connor J, Young R, Tucker J, McPherson A. Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: a single centres´ experience with pharmacotherapy. Alcohol Alcohol 2006; 41: 321-327.
• 29 Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us?. Alcohol Alcohol 2004; 39: 542-547.