High-potency benzodiazepines: recent clinical results

Abstract

As high-potency benzodiazepines, essentially alprazolam, clonazepam, and lorazepam, have been used to treat anxiety disorders for almost 2 decades, most efficacy and safety data appeared several years ago. The release of new formulations of 2 of them, clonazepam and alprazolam, invites review of these broadly effective anxiolytics. Clonazepam has recently become available in a lyophilized wafer that disintegrates when exposed to saliva and enhances ease of administration without altering its pharmacology, as shown by bioequivalence studies. Two U.S. multicenter trials carried out in the 1990s, among others, have provided strong confirmatory evidence for the use of clonazepam in panic disorder. Other recently published data on clonazepam pertain to its use as augmentation therapy with selective serotonin reuptake inhibitors and in the prevention of recurrences of major depressive disorder. A new, extended-release formulation of alprazolam now allows for once-daily rather than t.i.d. or q.i.d. dosing. With extended release, the blood drug concentrations of alprazolam remain within the therapeutic window for several hours, which should reduce fluctuation in therapeutic effect and curb the clock-watching phenomenon between doses. The literature concerning the use of this new formulation of alprazolam in panic disorder is reviewed.