Aripiprazole: A Drug with a Novel Mechanism of Action and Possible Efficacy for Alcohol Dependence

Alcohol dependence is a costly and socially devastating illness. The dopamine system has received increased attention due to the consensus that dopaminergic dysfunction is at the core of the addiction process. Agents that modulate this system might be beneficial in reducing craving, reward, and relapse. Aripiprazole is a 3(rd) generation atypical antipsychotic U.S. Food and Drug Administration-approved for the treatment of schizophrenia, bipolar disorder, and treatment-resistant major depression. Its principal mechanism of action appears to be associated with partial agonism at the D(2) dopamine receptor. Nevertheless, relatively recent pre-clinical data shows that aripiprazole might exert its action by way of agonism, partial agonism, and antagonism at both dopamine and serotonin receptors. In animal models of alcoholism aripiprazole produced an overall decrease in drinking behavior. Clinical trials with aripiprazole in alcoholics have shown some positive, but inconsistent, results. Given aripiprazole's putative activity on frontal-subcortical circuits subserving reward/craving and impulsive behavior, it might prove to be beneficial for neuropsychiatric conditions in which dysregulation of reward and impulsivity, among them alcoholism, are at the core of the syndrome. This article proposes a potential role for aripiprazole in alcoholism treatment, and suggests that more randomized controlled trials should be designed at appropriate doses to better understand aripiprazole's potential role as a treatment option. More options are needed to treat alcoholics that fall into different subgroups (e.g., those with impulsive disorders), or non-responsive to available treatments. Early results with aripiprazole are promising and warrant further exploration.