Symposium 17 Monday Sept. 24th 6.30 pm–8.00 pm; Room: Lecture Hall 1
Towards a personalized treatment of alcoholism: Chairpersons: Mann K (Germany), Berglund M (Sweden)
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Presentation S17-1
The cannabinoid receptor 1 antagonist SR 141716 (Rimonabant) for treatment of alcohol dependence—results from a placebo-controlled double-blind trial
Soyka M (Switzerland)
Background. Mulptiple lines of evidence suggest the endocannabinoid system to be implicated in the development of alcohol dependence. In addition, in the animal model the cannabinoid receptor 1 antagonist SR 141716 was found to decrease alcohol consumption.
Methods. This was a 12-week double-blind placebo-controlled concept-of-proof study to assess the possible efficacy of rimonabant 20 mg/day (2 x 10mg) in the prevention of relapse to alcohol in alcohol-dependent subjects.
Results. 260 subjects were included, 258 exposed to medication. 208 (80.6%) were male. Patients had an alcohol history of 15 years on average. More patients in the rimonabant group (94/131, 71.7%) compared to placebo (79/127, 62.2%) completed treatment. Although there was a modest effect of rimonabant with respect to relapse rate, there were no statistically significant differences between treatment groups. 41.5% in the rimonabant group had relapsed to drinking at the end of the study compared to 47.7% in the placebo group. Differences were more marked in the patients who relapsed to heavy drinking: 27.7% versus 35.6%. Safety und tolerance of the drug was good. 6 patients (4.6%) in the rimonabant group permanently discontinued treatment due to side effects compared to 10 (7.9%) in the placebo group. Patients on rimonabant lost weight (–1,7kg) compared to baseline (placebo group unchanged). This was more marked in patients with higher BMI. In addition, there was a significant decrease in leptin levels in the rimonabant group compared to baseline.
Conclusion. Data from this study give modest evidence for rimonabant to be of interest in the treatment of alcohol dependence. Lack of efficacy in this study may be explained by a very high response rate in the placebo group and a relatively short treatment duration.
Presentation S17-2
Towards an individualized treatment in alcoholism: Project Predict
Mann K, Smolka MN and the Project Predict Research Group (Germany)
Previous attempts to identify predictors for the treatment response in alcoholism have mainly concentrated on social and personality variables. Project MATCH was such an attempt which finally failed. The same holds true for similar attempts in pharmacotherapy. Therefore, we set out for a large oligocentre trial ‘Project PREDICT’. 432 patients are randomly assigned to treatment with acamprosate, naltrexone or placebo. At baseline patients are assessed with a battery of interviews, questionnaires and biological examinations (e.g. genetics). Specific emphasis is put on patients' individual pathways into relapse. It is determined whether relapse drinking respresented a positive reinforcer (‘reward craving’) or a negative reinforcer (‘relief craving’). This is assessed with questionnaires, the startle reflex and fMRI. We hypothesize, that patients who are a priori identified as ‘positive reinforcers’ better respond to naltrexone. Negative reinforcers should benefit most from acamprosate.
All patients have been included by now. Preliminary analyses suggest that it seems indeed possible to distinguish between the two craving types. The equivalent of positive reinforcement in the startle reflex correlates with fMRI responses to cues with a positive valence of about 0.7. These methods might offer a platform for a targeted pharmacotherapy in alcoholism.
Presentation S17-3
Neramexane in alcoholism relapse prevention—Results of a randomized placebo controlled trial
Wiesbeck GA, Mann K, Althaus M, Boening J (Switzerland)
Aims. Neramexane (1-amino-1,3,3,5,5-pentamethylcyclohexane) is an un-competitive NMDA receptor antagonist with moderate affinity to the MK 801 binding site. In humans, the substance revealed a favourable safety/tolerability profile while it led to a progressive decrease in operant responding for alcohol in an ethanol self-administration model in rats. The present study was the first one to investigate the clinical efficacy of neramexane in alcohol relapse prevention.
Methods. A total of 236 alcohol-dependent men was randomised to a double-blind, parallel-group, placebo-controlled international multicentre trial. After detoxification, patients were treated with 40 mg/day neramexane or placebo over a period of 12 consecutive weeks (treatment period) succeeded by another 12 weeks of follow-up. The continuous abstinence rate after 12 weeks of treatment was defined as the primary parameter of efficacy. Secondary parameters were time to first drink, cumulative abstinence duration, the amount of alcohol consumed, continuous abstinence rate after 8, 16, 24 weeks and the intensity of craving.
Results. Across all parameters, there was no difference in efficacy between neramexane and placebo.
Conclusions. The findings suggest that neramexane cannot be recommended for maintaining abstinence in alcohol dependent subjects.