New and Old Drugs to Treat Alcohol Use Disorders

Abstract

Around 2 billion people consume alcoholic beverages worldwide, and almost 10% of the world’s population is affected by AlcoholUse Disorders (AUDs) [1]. Alcohol consumption is responsible for approximately 3.8% of all deaths [2] and accounts for 5.5% of the global burden of disease [3]. So far, only three drugs [Naltrexone (NTX), Acamprosate (ACM), and Disulfiram (DF)] have been approved by the Food and Drug Administration for the treatment of alcohol dependence [4]; however, emerging data from clinical trials suggest that these medications are relatively ineffective in maintaining the abstinence from alcohol. The predict study conducted in Germany by Mann et al. [5] clearly documented that neither ACM nor NTX are more efficient than placebo in reducing the number of relapses throughout the complete treatment period and the subsequent 18 months of follow-up. The results of the predict study have been compared with those of the COMBINE trial performed in the United States (US) [6]. The main outcome of the predict study was the time elapsed before the first episode of heavy drinking, and, contrary to the positive NTX effect reported by the combine study, neither ACM nor NTX provided an additional benefit compared with placebo. It is worth noting that patients drank a significantly greater amount of alcohol before enrolment and more often fulfilled DSM-IV criteria for alcohol dependence in the predict than in the combine study, suggesting that the patient populations included in these trials were substantially different. A similar lack of efficacy also emerged from a previous European trial where NTX plus ACM were more effective than placebo and ACM alone in reducing episodes of heavy drinking, but not NTX alone [7]. A meta-analysis published a few years ago [8] stated that neither NTX nor ACM were able to maintain complete abstinence from alcohol; rather, these agents are effective in reducing relapses and the number of drinks per drinking days, and, consequently, the organ damage caused by alcohol consumption. The main aim in treating alcohol dependence is complete abstinence. In the light of the results of the studies reported above, ACM and NTX should be rationally indicated only when this purpose cannot be achieved, with the aim of reducing alcohol intake and, therefore, achieve a “harm reduction”. Indeed, total abstinence was obtained in an equivalent proportion of patients both in predict and combine studies, i.e. 39.3% and 38.9% respectively. Nevertheless, NTX and ACM remain the first line of pharmacological treatment for alcohol dependence. Are there any other pharmacological possibilities? An interesting position was expressed by Jonathan Chick and David Nutt in their “perspective” paper which appeared in 2011: “For a condition where existing therapies are only effective in a proportion of patients, and which has high morbidity and mortality, the time now seems right for reappraising the use of substitute prescribing for alcohol dependence” [9].