Alcohol craving reduced by drugs
Twin research projects have offered both present and future hope to people suffering from alcohol addiction.
US researchers say that epilepsy drug topiramate boosts general health as well as cutting the craving for drink.
A UK specialist said the potential side-effects of topiramate still merited caution.
A separate project showed that a single injection of a protein into the brains of rats almost immediately stopped them wanting alcohol.
Topiramate is not licensed in the UK for the treatment of alcohol addiction, although doctors are allowed to prescribe it if they wish, and occasionally do. The latest study results, published in the journal Archives of Internal Medicine, could increase the number of doctors willing to do this.
Researchers from the University of Virginia analysed the results of the US-wide trial, which took 371 people with a heavy drinking problem, and gave them either topiramate or a placebo "dummy" drug.
They found, that over 14 weeks, those taking topiramate not only had fewer obsessive thoughts and compulsions about using alcohol, but had generally improving health.
Their weight, cholesterol and blood pressure dropped, and levels of liver enzymes linked to "fatty liver" disease, the forerunner of cirrhosis, also fell away.
Lead researcher Professor Bankole Johnson said: "What we've found is that topiramate treats the alcohol addiction, not just the 'symptom' of drinking."
Dr Jonathan Chick, a specialist in the psychiatry of addiction, welcomed the results, particularly the figures which proved better health, rather than relying on an estimate of reduced drinking levels, which could prove misleading.
He said: "There are other drugs which were originally developed to prevent epileptic seizures, which have also shown promise in reducing relapse in alcoholism, but topiramate is so far the most convincing."
However, he said that his own limited use of topiramate had been very carefully monitored to minimise the powerful side-effects of the drug.
In the other study, the Proceedings of the National Academy of Sciences Journal reported on a study in rats carried out at the University of California at San Francisco.
The scientists injected a brain protein called GDNF directly into a part of the brain called the ventral tegmental area, which is thought to be heavily involved in "drug-seeking" behaviour.
The rats were placed in an environment designed to mimic human social drinking, with a lever that could be pushed to deliver an alcoholic drink.
The protein began working almost immediately, with effects noticed within 10 minutes.
The research also suggested that other cravings were unaffected, as the rats' desire for their supply of sugary water continued unabated.
In addition, once treated with GDNF, rats seemed to be less likely to "relapse" to alcoholism after a "rehab" situation, in which the alcohol supply was cut off for a period of time, then reintroduced.
"Our findings open the door to a promising new strategy to combat alcohol abuse, addiction and especially relapse," said lead author Dr Dorit Ron.
Dr Chick said that there had been various attempts to interfere directly with the brain systems controlling alcohol cravings, although these had only achieved "mixed success" when transferred from experimental animals to humans.
BBC NEWS | Health | Alcohol craving reduced by drugs
Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment: US multisite randomized controlled trial.
Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Addolorato G, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O'Malley SS, Swift RM; Topiramate for Alcoholism Advisory Board; Topiramate for Alcoholism Study Group.
Collaborators (32) Ait-Daoud N, Anthenelli RM, Anton RF, Guschwan M, Johnson BA, Kranzler HR, Lapham SC, Levin F, Longo L, Moeller FG, O'Malley SS, Pettinati HM, Salloum I, Sarid-Segal O, Swift RM, Trautman RP, Weiss RD, Addolorato G, Ait-Daoud N, Anton RF, Ciraulo DA, DiClemente CC, Hemby SE, Hollander E, Johnson BA, Kiefer F, Kranzler HR, Lesch OM, Malcolm RJ Jr, Mann K, O'Malley SS, Swift RM.
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908-0623, USA. email@example.com
BACKGROUND: Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating gamma-aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system. We sought to determine whether topiramate's antidrinking effects are bolstered by improvements in physical and psychosocial well-being. METHODS: In a 17-site, 14-week, double-blind, randomized controlled trial, we compared the effects of topiramate (up to 300 mg/d) vs placebo on physical health, obsessional thoughts and compulsions about using alcohol, and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy. RESULTS: Topiramate was more efficacious than placebo in reducing body mass index (calculated as weight in kilograms divided by height in meters squared) (mean difference, 1.08; 95% confidence interval [CI], 0.81-1.34; P < .001), all liver enzyme levels (P < .01 for all comparisons), plasma cholesterol level (mean difference, 13.30 mg/dL; 95% CI, 5.09-21.44 mg/dL; P = .002), and systolic (mean difference, 9.70 mm Hg; 95% CI, 6.81-12.60 mm Hg; P < .001) and diastolic (mean difference, 6.74 mm Hg; 95% CI, 4.57-8.90 mm Hg; P < .001) blood pressure to about prehypertension levels-effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease. Topiramate compared with placebo significantly (P < .05 for all comparisons) decreased obsessional thoughts and compulsions about using alcohol, increased subjects' psychosocial well-being, and improved some aspects of quality of life, thereby diminishing the risk of relapse and longer-term negative outcomes. Paresthesia, taste perversion, anorexia, and difficulty with concentration were reported more frequently for topiramate than for placebo. CONCLUSION: Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects.
Improvement of physical health and quality of life...[Arch Intern Med. 2008] - PubMed Result
Interesante esto... habia un par de articulos en pubmed que ademas mencionaban la naltrexona.Topiramate may modulate alcohol abuse but not other compulsive behaviors in frontotemporal dementia: case report.
Cruz M, Marinho V, Fontenelle LF, Engelhardt E, Laks J.
Drug Abuse Research and Assistance Program, Institute of Psychiatry, Federal University of Rio de Janeiro, RJ, Brazil. firstname.lastname@example.org
Frontotemporal dementia (FTD) is an insidious presenile neurodegenerative disorder presenting with personality changes, compulsive behaviors, psychosis, apathetic, aberrant, and elated mood and behavior. No psychopharmacologic strategy has proven to be efficacious in the treatment of FTD yet. This is a case report of FTD in a 53-year-old male engineer whose alcohol abuse, but not other compulsive behaviors, responded to topiramate. Alcohol exerts reinforcing effects on cortico-mesolimbic dopamine pathways through the disinhibition of the inhibitory effects of gamma-amino-butyric acid-A neurons in the ventral tegmental area. Topiramate is a sulfamate-substituted fructopyranose derivative that may antagonize the reinforcing effects associated with the abuse liability of alcohol by modulation of cortico-mesolimbic dopamine function. On the basis of the mechanism of action of topiramate, we discuss the possible specificity of action of topiramate to control abusive drinking, but not to treat other clinical symptoms of FTD.
Topiramate may modulate alcohol abuse but not othe...[Cogn Behav Neurol. 2008] - PubMed Result