Abstract

Predicated upon a neuropharmacological conceptual model, there is now solid clinical evidence to support the efficacy of topiramate for the treatment of alcohol dependence. Topiramate treatment can be initiated whilst the alcohol-dependent individual is still drinking — just when crisis intervention is most likely to be needed by a patient with or without his or her family asking the health practitioner for assistance. Because topiramate can be paired with a brief intervention, there is now the exciting possibility of treating most alcohol- dependent individuals in office-based practice or generic treatment settings. Topiramates additional effects on other impulsedyscontrol disorders make it a particularly interesting compound for the treatment of other comorbid drug or psychiatric disorders. Additionally, future studies should explore whether topiramate can be combined with other putative therapeutic agents to increase its efficacy. One notable clinical challenge in the development of topiramate as a pharmacotherapy to treat alcohol dependence is the determination of the smallest dose that can result in efficacy, thereby achieving the optimum balance between therapeutic benefit and adverse event profile. Animal data do provide support for topiramates general anti-drinking effects but also indicate that its mechanisms of action might rely on several complex pharmacobehavioral changes. Additional preclinical studies are needed to elucidate more clearly the basic mechanistic processes that underlie topiramates efficacy as a treatment for alcohol dependence. Preclinical information that topiramate may have differential effects based on genetic vulnerability opens up the possibility of future methods to optimize treatment.

Keywords: Topiramate, alcohol, treatment, glutamate, gamma-aminobutyric acid, craving, impulsivity, relapse