Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound

Low and medium potency benzodiazepines were initially introduced for the treatment of insomnia and anxiety. Their therapeutic actions as anxiolytics, sedative hypnotics, anticonvulsants, and muscle relaxants (with their low toxicity) have led to their use as first-line treatments, and they have become one of the most prescribed classes of drugs. Novel therapeutic uses of benzodiazepines were discovered with the introduction of the high-potency benzodiazepines (e.g., alprazolam, clonazepam, and lorazepam). They were found to be effective in treating panic disorder and panic attacks with or without agoraphobia, as add-on therapy to selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder and panic disorders, and as adjunctive therapy in treating patients with acute mania or acute agitation. High-potency benzodiazepines have replaced low and medium potency benzodiazepines in all benzodiazepine clinical indications due to their greater therapeutic effects and rapid onset of action. Differences in distribution, elimination half-life, and rate of absorption are important considerations when choosing a high-potency benzodiazepine. Typically, a benzodiazepine with long distribution and elimination half-lives is preferred. A maximum dose of 2 mg/day of any of the high-potency benzodiazepines when given for more than 1 week is recommended. Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome.