Anxiolytics and the Treatment of Anxiety Disorders

Fundamentals of Psychopharmacology. Third Edition. By Brian E. Leonard 2003 John Wiley Sons, Ltd. ISBN 0 471 52178 7 

The half-life of a benzodiazepine is not predictive either of its onset of action or of the therapeutic response of the patient. Flowever, the rate of absorption and distribution within the body are important parameters in determining the pharmacodynamic response. The period for maximal response to treatment may be as long as 6 weeks, and there is no evidence 

The link between the serotonergic pathways and the control of anxiety has been further strengthened by the introduction of non-benzodiazepine anxiolytics such as buspirone, ipsapirone and gepirone, which decrease central serotonergic function by stimulating a subclass of 5-HT receptors (5- 

leading to a decrease in serotonergic release. Despite the connection between the decreased functional activity of the serotonergic system and the anxiolytic effects of the benzodiazepines, it would appear that their effect on serotonergic transmission is indirect and probably mediated via a facilitation of the principal inhibitory neurotransmitter, GABA. 

Several neuropeptides have been shown to play a role in anxiety but so far none has been developed as a drug largely because of their poor pharmacokinetic properties and difficulty in penetrating the blood-brain barrier. This situation may change in the future when drugs are developed that, though they may not be peptides, have a high affinity for the peptide receptors. 

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By the 1970s and early 1980s it was recognized that certain tricyclic antidepressants and monoamine oxidase (MAO) inhibitors were effective in treating panic disorder and one tricyclic antidepressant (clomipramine) was effective in treating obsessive-compulsive disorder. Thus, there began to be recognized that some antidepressants overlapped with anxiolytics for the treatment of anxiety disorder sub-types or for mixtures of anxiety and depression (Fig. 8—8). However, either anxiolytics... 

Benzodiazepines are amongst the most frequently prescribed drugs they have well-established uses in the treatment of anxiety disorders (anxiolytics) and insomnia, preanaesthetic sedation, suppression of seizures, and muscle relaxation. 

Buspirone (Buspar). The first nonsedating, nonbenzodiazepine specifically introduced as an anxiolytic, buspirone is FDA approved for the treatment of GAD. This medication acts as a partial agonist at the postsynaptic serotonin (5HT)-1A receptor. Like the antidepressants, buspirone has a delayed onset of action and effectively relieves the intrapsychic symptoms of GAD. Devoid of the muscle-relaxing properties of benzodiazepines, buspirone does not as effectively relieve the physical symptoms of GAD. Buspirone is not effective in the treatment of depression. Furthermore, its utility for the treatment of anxiety disorders other than GAD appears to be limited. 

In this chapter, we discuss the pharmacology of medications that are classified as anxiolytic, sedative, or hypnotic—primarily the benzodiazepines, buspirone, zolpidem, eszopiclone, and zale-plon. Subsequently, we present diagnosis-specific treatment guidelines (outlined in Table 3-1). The commonly used anxiolytics and hypnotics, together with their usual doses, are shown in Table 3-2. Many antidepressant medications are also effective in the treatment of anxiety disorders. The pharmacology of antidepressants is discussed in Chapter 2 their clinical use in anxiety disorders is addressed in the diagnosis-specific sections later in this chapter. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

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