Pharmakotherapie - Rückfallprophylaxe bei Alkoholabhängigkeit

Zusammenfassung

Mit zunehmendem Verständnis der neurobiologischen Grundlagen der Alkoholabhängigkeit wird der medikamentösen Rückfallprophylaxe immer mehr Bedeutung beigemessen. So genannte Anticraving-Substanzen steigern in Kombination mit psychotherapeutischen/psychosozialen Maßnahmen die bislang erreichten Behandlungserfolge beträchtlich. Besonders sind der NMDA-Rezeptorantagonist Acamprosat und der Opiatrezeptorantagonist Naltrexon zu nennen, deren Effekte in der Rückfallprophylaxe über zahlreiche Studien nachgewiesen werden konnten. Für Naltrexon fehlt allerdings in Deutschland die Zulassung in dieser Indikation. Werden die zur Abstinenz motivierten Patienten nach der Entgiftung ein Jahr mit Acamprosat rückfallprophylaktisch behandelt, verdoppelt sich die Zahl der Patienten, die auch über die eigentliche Behandlungszeit hinaus abstinent bleiben. Aktuelle Studien versuchen, besonders geeignete Untergruppen von Patienten („responder”) zu identifizieren, um dann - gezielt behandelt - in Zukunft den Erfolg der medikamentösen Rückfallprophylaxe weiter steigern zu können.

Summary

Better understanding of the neurobiological substrates of alcohol dependence has been accompanied with an increasing role of pharmacological relapse prevention. In combination with psychosocial treatment substances which reduce alcohol craving improve maintenance of abstinence. Especially the NMDA receptor antagonist acamprosate and the opiate receptor antagonist naltrexone showed an effect in numerous trials. In Germany, however, naltrexone has not been approved in this indication up to now. The administration of the medication starts immediately after detoxification and should last for twelve months. The medical treatment, however, is not a replacement for a psychosocial treatment of the alcohol dependence. Compared with placebo treatment, approximately twice as many patients remain abstinent under acamprosate one year after the end of the treatment period. Current studies try to identify particular subgroups of patients responding to pharmacological relapse prevention. A specific application of these substances will optimise the outcome of rehabilitation programmes for alcohol dependent patients.

alcohol dependence - relapse prevention - craving - naltrexone - acamprosate

Literatur

• 1 Ansoms C, Deckers F, Lehert P. et al. . An open study with acamprosate in Belgium and Luxemburg: results on sociodemographics, supportive treatment and outcome.  Eur Addict Res. 2000;  6 132-140
• 2 Anton RF, Moak DH, Waid LR. et al. . Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial.  Am J Psychiatry. 1999;  156 1758-1764
• 3 Barrias JA. et al. . Acamprosate : Estudo português, multicêntrico de avaliaçao da eficacia e tolerância [Acamprosate: multicenter Portuguese efficacy and tolerance evaluation study].  Psiquiatr Clin. 1997;  18 149-160
• 4 Besson J, Aeby F, Kasas A. et al. . Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.  Alcohol Clin Exp Res. 1998;  22 573-579
• 5 Chick J, Howlett H, Morgan MY, Ritson B. United Kingdom Multicentre Acamprosate Study (UKMAS): a 6-month prospective study of acamprosate versus placebo in preventing relapse after withdrawal from alcohol.  Alcohol Alcohol. 2000;  35 176-187
• 6 Cornelius JR, Salloum IM, Ehler JG. et al. . Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial.  Arch Gen Psychiatry. 1997;  54 700-705
• 7 Ehrenreich H. et al. . ALITA - Neue Wege in der ambulanten Intensivbehandlung von Alkoholabhängigen.  In: Mann K (Hrsg). Neue Therapieansätze bei Alkoholproblemen.  Lengerich: Pabst. 2002;  107-118
• 8 Froehlich JC, Harts J, Lumeng L, Li TK. Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference.  Pharmacol Biochem Behav. 1990;  35 385-390
• 9 Fuller RK, Branchey L, Brightwell DR. et al. . Disulfiram treatment of alcoholism. A veterans administration cooperative study.  JAMA. 1986;  256 1449-1455
• 10 Garbutt JC, West SL, Carey TS. et al. . Pharmacological treatment of alcohol dependence: a review of the evidence.  JAMA. 1999;  281 1318-1325
• 11 Gastpar M, Bonnet U, Bohning J. et al. . Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study.  J Clin Psychopharmacol. 2002;  22 592-598
• 12 Geerlings PJ, Ansoms C, van Den BW. Acamprosate and prevention of relapse in alcoholics. Results from a randomized, placebo-controlled double-blind study in out-patient alcoholics in the Netherlands, Belgium and Luxembourg.  Eur Addict Res. 1997;  3 129-137
• 13 Gual A, Lehert P. Acamprosate during and after acute alcohol withdrawal: a double-blind placebo-controlled study in Spain.  Alcohol Alcohol. 2001;  36 413-418
• 14 Johnsen J, Morland J. Disulfiram implant: a double-blind placebo controlled follow-up on treatment outcome.  Alcohol Clin Exp Res. 1991;  15 532-536
• 15 Johnson BA, Roache JD, Javors MA. et al. . Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial.  JAMA. 2000;  284 963-971
• 16 Kiefer F, 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
• 17 Krystal JH, Cramer JA, Krol WF. et al. . Naltrexone in the treatment of alcohol dependence.  N Engl J Med. 2001;  345 1734-1739
• 18 Ladewig D, Knecht T, Leher P, Fendl A. Acamprosate - a stabilizing factor in long-term withdrawal of alcoholic patients.  Ther Umsch. 1993;  50 182-188
• 19 Lhuintre JP, Daoust M, Moore ND. et al. . Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics.  Lancet. 1985;  1 1014-1016
• 20 Lhuintre JP, Moore N, Tran G. et al. . Acamprosate appears to decrease alcohol intake in weaned alcoholics.  Alcohol Alcohol. 1990;  25 613-622
• 21 Mason BJ, Ritvo EC, Morgan RO. et al. . A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence.  Alcohol Clin Exp Res. 1994;  18 1162-1167
• 22 Mueller TI, Stout RL, Rudden S. et al. . A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence.  Alcohol Clin Exp Res. 1997;  21 86-92
• 23 Namkoong K, Lee BO, Lee PG. et al. . Acamprosate in korean alcohol-dependent patients: a multi-centre, randomized, double-blind, placebo-controlled study.  Alcohol Alcohol. 2003;  38 135-141
• 24 O'Malley SS, Jaffe AJ, Chang G. et al. . Naltrexone and coping skills therapy for alcohol dependence. A controlled study.  Arch Gen Psychiatry. 1992;  49 881-887
• 25 Paille FM, Guelfi JD, Perkins AJ. et al. . Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol.  Alcohol Alcohol. 1995;  30 239-247
• 26 Pelc I, Le O Bon, Verbanck P. et al. . Novel pharmacological interventions for alcoholism.  In: Naranjo C, Sellers EM (Hrsg).  New York: Springer. 1992;  348-352
• 27 Pelc I, Verbanck P, Le O Bon. et al. . Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo-controlled dose-finding study.  Br J Psychiatry. 1997;  171 73-77
• 28 Poldrugo F. Acamprosate treatment in a long-term community-based alcohol rehabilitation programme.  Addiction. 1997;  92 1537-1546
• 29 Roussaux JP, Hers D, Ferauge M. Does acamprosate diminish the appetite for alcohol in weaned alcoholics?.  J Pharm Belg. 1996;  51 65-68
• 30 Sass H, Soyka M, Mann K, Zieglgansberger W. Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence.  Arch Gen Psychiatry. 1996;  53 673-680
• 31 Tempesta E, Janiri L, Bignamini A. et al. . Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo-controlled study.  Alcohol Alcohol. 2002;  35 202-209
• 32 Verheul R, Van BW Den, Geerlings P. A three-pathway psychobiological model of craving for alcohol.  Alcohol Alcohol. 1999;  34 197-222
• 33 Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence.  Arch Gen Psychiatry. 1992;  49 876-880
• 34 Whitworth AB, Fischer F, Lesch OM. et al. . Comparison of acamprosate and placebo in long-term treatment of alcohol dependence.  Lancet. 1996;  347 1438-1442

Anschrift für die Verfasser