The role of extended-release benzodiazepines in the treatment of anxiety: A risk-benefit evaluation with a focus on extended-release alprazolam

Immediate-release (IR) benzodiazepines have a short duration of therapeutic effect and are generally less effective for anxiety than selective serotonin reuptake inhibitors in reducing concomitant depressive symptomatology. Common criticisms of benzodiazepines also include the patient's tendency to develop a tolerance to the anxiolytic effect and a dependence on the drug itself. The newer extended-release (XR) benzodiazepine formulation was designed to increase efficacy, duration of therapeutic effect, tolerance, compliance, and ease of discontinuation. The XR benzodiazepine alprazolam has shown efficacy in panic disorder and generalized anxiety disorder comparable to the older benzodiazepine formulations. Pharmacokinetic data show that the XR formulation has a longer therapeutic effect compared with IR formulations, which reduces the potential for breakthrough anxiety symptoms. Data also indicate that the XR formulation has less abuse liability than the IR formulation. This article reviews the efficacy, safety, and discontinuation data from clinical trials of IR and XR benzodiazepines in the treatment of anxiety disorders and provides guidelines to minimize the risk of withdrawal syndrome during benzodiazepine discontinuation.