# SAT1.1 RISK FACTORS FOR ALCOHOL DEPENDENCE {#article-title-2} Alcohol dependence is a complex genetically influenced brain disease. This lecture reviews the evidence that supports the importance of genetic influences in this condition, and describes one aspect of the search for the genetic and environmental characteristics that contribute to the vulnerability toward heavy drinking and alcohol problems. Most risk factors operate indirectly on the predisposition toward alcohol dependence by affecting how alcohol is metabolized, operate through personality characteristics such as impulsive behaviours that increase the risk for all substance-related problems, relate to several psychiatric disorders, or affect how a person's brain reacts to alcohol. One of the most thoroughly studied of the genetically influenced mechanisms relating to how a person responds to alcohol is a low level of response, or low sensitivity, to alcohol. This characteristic is used to demonstrate how research has identified risk factors, established whether there are genetic influences for these characteristics, discovered environmental characteristics that impact on how the genetically-influenced factor affects the risk for alcohol dependence, identified brain mechanisms that contribute to the vulnerability, and then used these findings to develop and test a prevention approach to decrease the risk for heavy drinking and alcohol problems. # SAT1.2 AN EXTENSION OF THE CURRENT TREATMENT PARADIGM FOR ALCOHOL DEPENDENCE: RESULTS FROM NALMEFENE PHASE III TRIALS {#article-title-3} Treatment for alcohol depends has been focused on total abstinence using psychotherapeutic and pharmacological interventions. However, many alcohol-dependent individuals are not able or inclined to achieve total abstinence, resulting in a medical condition that is under-diagnosed and under-treated. In Europe, only a small fraction (8.3%) of the people diagnosed with alcohol dependence receives treatment. Nalmefene is an opioid system modulator with antagonist activity at the μ and δ opioid receptors and partial agonist activity at the κ opioid receptor. Three multi-centre, double-blind, placebo-controlled Phase III studies, designed to assess the efficacy and safety of nalmefene in reducing alcohol consumption, enrolled close to 2000 patients with alcohol dependence. Nalmefene as-needed has been shown to reduce the total amount of alcohol consumption and number of heavy drinking days and to improve liver functions and clinical status in two 6-month studies (identically designed), and one 1-year study in patients with alcohol dependence. The benefit of nalmefene was further studied in the pooled subgroup of patients from the 6-month studies. The patients in this subgroup were consuming alcohol at a high drinking risk level at the initial assessment (screening) and at the start of treatment (baseline). In this subgroup, identified as most likely to benefit, the net treatment effect over placebo in terms of reduction of alcohol consumption was more pronounced. # SAT1.3 CLINICAL DATA SUPPORTING THE BENEFIT OF A PATIENT-CENTRED APPROACH IN THE TREATMENT OF ALCOHOL DEPENDENCE {#article-title-4} A patient centred approach that offers the choice of reduction of alcohol consumption as part of a continuum of treatment goals and which allows patients to have a say in dosing regimens, may help reduce the barriers to treatment perceived by some individuals. Engaging patients in managing their treatment may also improve adherence. In three phase III studies assessing as-needed nalmefene in reducing alcohol consumption in alcohol dependent patients, it has been shown that alcohol dependent patients understand, accept and adhere to the “as-needed” dosing concept and that nalmefene as-needed reduces the average daily total alcohol consumption (TAC; g/day) and number of heavy drinking days (HDDs). The W.H.O. has defined risk categories for health problems based on the level of daily alcohol consumption. These categories can be used to define response, as a measure of the clinical relevance of the reduction in alcohol consumption at an individual patient level. Drinking variables (TAC and HDDs) were measured using Timeline Follow-Back. Various analyses were used to translate the reduction in alcohol consumption into clinically relevant responses. Response was defined as 1) two-category down-shift in drinking risk level; 2) downward shift to low drinking risk level; 3) 70% reduction in TAC; all at month 6. As-needed nalmefene was associated with each of these clinically relevant responses, supporting that the benefits of a patient-centered approach can be shown in clinical trials.