Benzodiazepines

The selection of a benzodiazepine should be based on an understanding of potency, rate of onset, route of metabolism, effective half-life, and clinically proven effectiveness. Although all benzodiazepines appear to function by common mechanisms, the particular combination of the above factors (and perhaps as yet unknown variations in affinity for receptor subtypes) produce varied clinical indications for different benzodiazepines. Table 14-2 illustrates the properties of some commonly used benzodiazepines and their common clinical uses.

Potency
The high-potency benzodiazepines alprazolam and clonazepam are used in the treatment of panic disorder.

Rate of Onset
Fast-onset benzodiazepines, such as diazepam, may produce a “high” feeling and are potentially more addictive. The fast-onset benzodiazepines flurazepam and triazolam are commonly used for insomnia, as is diazepam.

Route of Metabolism
All benzodiazepines listed, with the exception of lorazepam, oxazepam, and temazepam, require oxidation as a step in their metabolism. Because the oxidative functions of the liver are impaired with liver disease ( e.g., cirrhosis) or with a general decline in liver function (e.g., aging), benzodiazepines that require oxidation are more likely to accumulate to toxic levels in individuals with impaired liver function.

Elimination Half-Life
The elimination half-life depicts the effective duration of action of the metabolized medications. For medications with long elimination half-lives, toxicity can easily occur with repetitive dosing. In addition, toxicology screens may remain positive for several days after the last dose of a long-acting benzodiazepine. Drugs with longer elimination half-lives offer less likelihood of interdose symptom rebound.

For example, clonazepam is now favored over alprazolam in the treatment of panic because its longer elimination half-life provides better interdose control of panic symptoms. Medications with shorter elimination half-lives are useful for conditions such as insomnia because they are less likely to produce residual daytime sedation or grogginess.

Active Metabolites
Medications with active metabolites generally have a longer elimination half-life. Among the benzodiazepines, all but three drugs metabolized by conjugation (lorazepam, oxazepam, temazepam) and clonazepam have active metabolites.

Buspirone
Buspirone is indicated for the treatment of GAD.

Because of its long lag time to therapeutic effect, patients with severe anxiety symptoms may be unable to sustain a clinical trial. Buspirone is favored as a treatment in individuals with a history of substance or benzodiazepine abuse. In general, buspirone lacks the reliability of benzodiazepines in relieving anxiety but can be effective in some people.