A rational approach to the pharmacotherapy of alcohol dependence.

The use of alcohol is widespread in the world, and although there are many regular users, some individuals drink excessively. Understanding the time course of the development and maintenance of alcohol dependence is important in assessing the potential risk/benefit of an intervention and in accurately treating the problem. Most, although not all, literature suggests that alcoholism is a chronic, relapsing disorder and that there is a general progression from less to more severe problems. Understanding the neurobiology that underlies alcohol dependence as it relates to different clinical stages may help in the development of effective targeted pharmacological treatments. Important clinical stages that may be amenable to pharmacological intervention include the transition from alcohol use to heavy drinking particularly in vulnerable individuals, the cessation of heavy drinking in individuals who want to quit, and the prevention of relapse in individuals who have initiated abstinence but may struggle with craving or the desire to resume alcohol use. Neurotransmitter systems implicated in these stages include glutamate, gamma-aminobutyric acid, opioid, and serotonin systems that may act directly or via the indirect modulation of dopamine function. The treatment implications will also be discussed.