Guidelines for the clinical use of benzodiazepines: pharmacokinetics, dependency, rebound and withdrawal. Canadian Society for Clinical Pharmacology.

Principles of benzodiazepine selection are outlined for various psychiatric indications and diverse populations (the elderly, and drug and alcohol abusers). Benzodiazepines are still among the most commonly used classes of medications, and they differ in their pharmacodynamic properties. They have varied uses as monotherapy or as adjunctive medication because of their efficacy in the treatment of conditions involving a dysfunction of the GABAergic system or where neuronal inhibition is required. In multiple therapy, benzodiazepines augment the efficacy of other drugs such as lithium in mania, antipsychotics in psychotic agitation and selective serotonin reuptake inhibitors in panic disorder. Benzodiazepines can produce dependence and tolerance in most patients; predisposed individuals are at greater risk. Short- and intermediate-beta half-life compounds carry a greater risk of rebound and withdrawal reactions, and drug dependence than long acting agents. Adverse effects include sedation, psychomotor and cognitive impairment, memory loss, potentiation of other central nervous system depressants and treatment-emergent depression. Drug potency and beta elimination half-life are reviewed and compared as pharmacokinetic variables.