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 generallyless effective for anxiety than selective serotonin reuptake inhibitors in reducing concomitant depressivesymptomatology. Common criticisms of benzodiazepines also include the patient’s tendencyto develop a tolerance to the anxiolytic effect and a dependence on the drug itself. The newerextended-release (XR) benzodiazepine formulation was designed to increase efficacy, duration oftherapeutic effect, tolerance, compliance, and ease of discontinuation. The XR benzodiazepine alprazolamhas shown efficacy in panic disorder and generalized anxiety disorder comparable to the olderbenzodiazepine formulations. Pharmacokinetic data show that the XR formulation has a longer therapeuticeffect compared with IR formulations, which reduces the potential for breakthrough anxietysymptoms. 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 XRbenzodiazepines in the treatment of anxiety disorders and provides guidelines to minimize the risk ofwithdrawal syndrome during benzodiazepine discontinuation.