The medications discussed in this section have anxiolysis in common. Although benzodiazepines have a wide variety of clinical applications (e.g., as pre anesthetics, in the treatment of status epilepticus, as muscle relaxants, and in the treatment of insomnia) and other medications (e.g., antidepressants) are of utility in treating some forms of anxiety, the benzodiazepines are uniquely effective for the rapid relief of a broad spectrum of anxiety symptoms. Buspirone is a novel medication that, at present, is used primarily in the treatment of generalized anxiety disorder (GAD); it does not appear to be effective in treating other types of anxiety (e.g., panic).

Indications

Benzodiazepines
Benzodiazepines are among the most widely used drugs in all of medicine. In psychiatry they are used as the primary treatment of a disorder or as adjunct treatment to other pharmacologic agents. Benzodiazepines are used to treat a variety of anxiety disorders: panic disorder, generalized anxiety disorder (GAD), anxiety associated with stressful life events (as in adjustment disorders with anxiety), and anxiety that complicates depression.

In addition, benzodiazepines are used for the shortterm treatment of insomnia, for the treatment of alcohol withdrawal, for the agitation of mania, dementia, and psychotic disorders, and in the treatment of catatonia (Table 14-1).

Buspirone (Buspar)
Buspirone is used primarily for generalized anxiety disorder.

Mechanism of Action

Benzodiazepines
Benzodiazepines appear to function as anxiolytics via their agonist action at the central nervous system (CNS) GABA_A (gamma-amino-butyric-acid) receptors (the GABA_A receptor complex regulates a chloride ion channel, GABA_B receptors appear to work by second messenger systems). GABA is a widespread inhibitory neurotransmitter with a complicated receptor structure, having multiple binding sites for GABA, benzodiazepines, and barbiturates.

The most likely mode of action of benzodiazepines in treating psychiatric illnesses is via their augmentation of GABA function in the limbic system.

Because benzodiazepines are direct agonists at a rapidly responding ion channel, their mechanism of action is virtually instantaneous with their arrival in the CNS (in contrast to buspirone, see below).

Buspirone
Buspirone is a novel medication that appears to act as an anxiolytic via its action as an agonist at the serotonergic 5HT _1α]a receptor. In addition, it has some D₂ antagonist effects, although with unclear clinical significance. Unlike the benzodiazepines, it does not work rapidly; a period of several weeks of sustained dosing is required to obtain symptomatic relief Buspirone has no GABA receptor affinity and is therefore not useful in treating benzodiazepine or alcohol withdrawal. It is not a sedative and is not useful in treating insomnia.