Subscribe to RSS
DOI: 10.1055/s-2004-818986
Hypothalamic-Pituitary-Adrenal System Regulation in Recently Detoxified Alcoholics Is Not Altered by One Week of Treatment with Acamprosate
Publication History
Received: 16.8.2002
Revised: 14.11.2002
Accepted: 6.3.2003
Publication Date:
12 May 2004 (online)
Background: Acamprosate decreases relapse rates in alcohol-dependent patients by approximately 10-20 % within the first year after detoxification. Psychological stress is a major risk factor for relapse and is associated with activation of the hypothalamic-pituitary-adrenocortical (HPA) system. In recently detoxified alcoholics, the HPA system is dysregulated with non-suppression of cortisol after dexamethasone administration. We therefore investigated whether acamprosate normalizes HPA hyperactivity in alcoholics within the first 3 weeks of abstinence, employing a combined dexamethasone/corticotropin-releasing hormone (Dex-CRH)-test. Methods: Thirty alcohol-dependent patients were tested one week after withdrawal signs had disappeared. In 15 patients, acamprosate, 1332-1998 mg/day, was administered orally and a second Dex-CRH test was performed 1 week later. In the other 15 patients, acamprosate treatment was offered only after the second test. Results: CRH-stimulated cortisol secretion was significantly increased in both the acamprosate group and the group receiving no anti-relapse medication compared to a control group of 15 healthy subjects. Acamprosate treatment had no effect on basal or CRH-stimulated ACTH or cortisol secretion. Conclusions: We conclude that 1 week of acamprosate treatment does not attenuate the HPA dysregulation observed during early abstinence.
References
- 1 Adinoff B, Martin P R, Bone G HA, Eckardt M J, Roehrich L, George D T, Moss H B, Eskay R, Linnoila M, Gold P W. Hypothalamic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence. Arch Gen Psychiat. 1990; 47 325-330
- 2 al Qatari M, Khan S, Harris B, Littleton J. Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain. Alcohol Clin Exp Res. 2001; 25 1276-1283
- 3 Berton F, Francesconi W G, Madamba S G, Zieglgansberger W, Siggins G R. Acamprosate enhances N-methyl-D-apartate receptor-mediated neurotransmission but inhibits presynaptic GABA(B) receptors in nucleus accumbens neurons. Alcohol Clin Exp Res. 1998; 22 183-191
- 4 Brady K T, Sonne S C. The role of stress in alcohol use, alcoholism treatment, and relapse. Alcohol Res Health. 1999; 23 263-271
- 5 Dahchour A, De Witte P. Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog Neurobiol. 2000; 60 343-362
- 6 Feuerlein W, Ringer C, Kufner H, Antons K. Diagnosis of alcoholism: the Munich Alcoholism Test (MALT). Curr Alcohol. 1979; 7 137-147
- 7 Gerra G, Caccavari R, Delsignore R, Vourna S, Maestri D, Ugolotti G, Passeri M. Pituitary responses to Ca-acetyl-homotaurinate in normal subjects and alcoholics. Neuroendocrinol Lett.. 1992; 14 119-126
- 8 Heinz A, Jones D W, Bissette G, Hommer D, Ragan P, Knable M, Wellek S, Linnoila M, Weinberger D R. Relationship between cortisol and serotonin metabolites and transporters in alcolholism. Pharmacopsychiatry. 2002; 35 127-134
- 9 Heyser C J, Schulteis G, Durbin P, Koob G F. Chronic acamprosate eliminates the alcohol deprivation effect while having limited effects on baseline responding for ethanol in rats. Neuropsychopharmacology. 1998; 18 125-133
- 10 Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000; 23 477-501
- 11 Hundt W, Zimmermann U, Pöttig M, Hahn K, Holsboer F. The combined dexamethasone suppression/ CRH stimulation test in alcoholics during and after acute withdrawal. Alcohol Clin Exp Res. 2001; 25 687-691
- 12 Jezova D, Tokarev D, Rusnak M. Endogenous excitatory amino acids are involved in stress-induced adrenocorticotropin and catecholamine release. Neuroendocrinology. 1995; 62 326-332
- 13 Madamba S G, Schweitzer P, Zieglgansberger W, Siggins G R. Acamprosate (calcium acetylhomotaurinate) enhances the N-methyl- D-aspartate component of excitatory neurotransmission in rat hippocampal CA1 neurons in vitro. Alcohol Clin Exp Res. 1996; 20 651-658
- 14 Mayer S, Harris B R, Gibson D A, Blanchard J A, Prendergast M A, Holley R C, Littleton J. Acamprosate, MK-801, and ifenprodil inhibit neurotoxicity and calcium entry induced by ethanol withdrawal in organotypic slice cultures from neonatal rat hippocampus. Alcohol Clin Exp Res. 2002; 26 1468-1478
- 15 Naassila M, Hammoumi S, Legrand E, Durbin P, Daoust M. Mechanism of action of acamprosate. Part I. Characterization of spermidine-sensitive acamprosate binding site in rat brain. Alcohol Clin Exp Res. 1998; 22 802-809
- 16 Oliver C, Jezova D, Grino M et al., Brann D W, Mahesh V B, editors. Excitatory amino acids. Their role in neuroendocrine function. 1 ed. Vol. 5, Excitatory amino acids and the hypothalamic-pituitary-adrenal axis. Boca Raton; CRC Press 1996: 167-185
- 17 Pelc I, Verbanck P, Le Bon O, Gavrilovic M, Lion K, Lehert P. Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo- controlled dose-finding study. Br J Psychiat. 1997; 171 73-77
- 18 Popp R L, Lovinger D M. Interaction of acamprosate with ethanol and spermine on NMDA receptors in primary cultured neurons. Eur J Pharmacol. 2000; 394 221-231
- 19 Rammes G, Mahal B, Putzke J, Parsons C, Spielmanns P, Pestel E, Spanagel R, Zieglgansberger W, Schadrack J. The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801. Neuropharmacology. 2001; 40 749-760
- 20 Ravi S D, Dorus W, Park Y N, Collins M C, Reid R W, Borge G F. The dexamethasone suppression test and depressive symptoms in early and late withdrawal from alcohol. Am J Psychiat. 1984; 141 1445-1448
- 21 Sass H, Soyka M, Mann K, Zieglgansberger W. Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence. Arch Gen Psychiat. 1996; 53 673-680
- 22 Schule C, Laakmann G, Baghai T, Neukam C, Soyka M. Lack of effects of acamprosate on anterior pituitary hormone secretion in healthy subjects [letter]. J Clin Psychopharmacol. 1999; 9 387-389
- 23 Spanagel R, Hölter S M, Allingham K, Landgraf R, Zieglgansberger W. Acamprosate and alcohol. 1. Effects on alcohol intake following alcohol deprivation in the rat. Eur J Pharmacol. 1996; 305 39-44
- 24 Sullivan J T, Sykora K, Schneiderman J, Naranjo C A, Sellers E M. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989; 84 1353-1357
- 25 Tsai G, Gastfriend D R, Coyle J T. The glutamatergic basis of human alcoholism. Am J Psychiat. 1995; 152 332-340
- 26 Wetterling T, Veltrup C, Junghanns K, Kromer-Olbrisch T, Schneider U. Acceptance of pharmacotherapy for relapse prevention by chronic alcoholics. Pharmacopsychiatry. 2001; 34 142-146
- 27 Whitworth A B, Fischer F, Lesch O M, Nimmerrichter A, Oberbauer H, Platz T, Potgieter A, Walter H, Fleischhacker W. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1995; 347 1438-1442
- 28 Zimmermann U, Hundt W, Spring K, Grabner A, Holsboer F. Hypothalamic-pituitary-adrenal system adaptation to detoxification in alcohol-dependent patients is affeced by family history of alcoholism. Biol Psychiat. 2003; 53 75-84
- 29 Zobel A W, Nickel T, Sonntag A, Uhr M, Holsboer F, Ising M. Cortisol response to the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression: A prospective study. J Psychiat Res. 2001; 35 83-94
Ulrich Zimmermann
Max Planck Institute of Psychiatry
Kraepelinstr. 10
80804 Munich
Germany
Phone: +49-89-30622-389
Fax: +49-89-30622-223
Email: zimm@mpipsykl.mpg.de