Antianxiety Effects

Benzodiazepines may depict two- or three-compartment disposition kinetics. For example, a benzodiazepine derivative given in a suitable dose at night may impose dose-dependent effects, in that the concentration attained at night may be in the hypnotic range, whereas the concentration of the drug or its active metabolite or metabolites during the following day may be sufficient to produce antianxiety effects. 

It is generally accepted that the pharmacology of benzodiazepine derivatives is identical qualitatively but varies quantitatively. In other words, the sedative, hypnotic, anticonvulsant, muscle relaxant, and anxiolytic properties reside to various degrees in all of them. Nevertheless, they do exhibit pharmacological specificity, making it necessary to select a particular drug for its desired therapeutic effect. 

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Anxiolytics are compounds that act primarily to refleve the symptoms of anxiety although such agents can also be used as anticonvulsants, sedatives, hypnotics, and anesthetic agents (see Anesthetics). The principal class of anxiolytics, the BZs, shows dependence HabiUty (5) whereas newer agents such as buspkone [36505-84-7] and ritanserine [8705-43-2] produce antianxiety effects via central serotoninergic systems (6). 

Antidepressants are commonly used to treat both acute withdrawal and persistent anxiety or insomnia. There is evidence to suggest that they are effective in relieving some acute abstinence symptoms, but it has been more difficult to establish their effectiveness in long-term discontinuation. Antidepressants with sedative and antianxiety effects are the preferred drugs. 

It is considered a second-line agent for GAD because of inconsistent reports of efficacy, delayed onset of effect, and lack of efficacy for comorbid depressive and anxiety disorders (e.g., panic disorder or SAD). It is the agent of choice in patients who fail other anxiolytic therapies or in patients with a history of alcohol or substance abuse. It is not useful for situations requiring rapid antianxiety effects or as-needed therapy. 

Fig. 10.25 Apolipoprotein E plus angiotensin-converting enzyme (ACE + APOE)-related antianxiety effect of a multifactorial treatment in patients with Alzheimer s disease...

Doxepin is a tricyclic antidepressant which also has antianxiety effects. The following is an abbreviated monograph for doxepin. For complete information, refer to the Tricyclic.Antidepressants.monograph. 

The efficacy of beta-blockers in the symptomatic relief of anxiety in adults has been established in over a dozen controlled trials (Neppe, 1989). In a number of countries, beta-blockers have been licensed for the treatment of anxiety disorders. Somatic manifestations of anxiety such as palpitations, diaphoresis, and tremor, rather than core psychological symptoms, were particularly responsive to beta-blocker treatment. In comparative trials that included patients with severe anxiety and panic attacks, the antianxiety effect of beta-blockers was, however, somewhat less powerful than that of benzodiazepines (Lader, 1988), with the exception of a small trial that compared alprazolam to propranolol (Ravaris et ah, 1991). Head-to-head comparisons of beta-blockers and selective serotonin reuptake inhibitors (SSRIs) are lacking. Performance and stress-related anxiety that may affect public performers, such as musicians or people taking an examination or giving a speech, seems to be particularly suited for beta-blocker treatment (Lader, 1988). Beta-blockers may be given on an as-required basis 1-2 hours before the stressful situation. 

Anxiety Exerts an antianxiety effect during nervousness and panic attacks. 

We think that buspirone may be the drug of choice for many patients with GAD who have not taken BZDs previously. Buspirone may also have an advantage in patients who have problems with BZD withdrawal symptoms. Increased antianxiety effects have been observed in some patients treated concurrently with low doses of buspirone and a BZD (Table 12-4). Further, buspirone may be indicated in individuals with GAD with histories of chemical dependency who have failed or who could not tolerate antidepressants ( 54). 

Benzodiazepines, barbiturates, and most older sedative-hypnotic drugs exert calming effects with concomitant reduction of anxiety at relatively low doses. In most cases, however, the anxiolytic actions of sedative-hypnotics are accompanied by some depressant effects on psychomotor and cognitive functions. In experimental animal models, benzodiazepines and older sedative-hypnotic drugs are able to disinhibit punishment-suppressed behavior. This disinhibition has been equated with antianxiety effects of sedative-hypnotics, and it is not a characteristic of all drugs that have sedative effects, eg, the... 

By producing sedation, many drugs will also decrease the level of anxiety in a patient. Of course, these anxiolytic properties often cause a decrease in the level of alertness in the individual. However, certain agents are available that can reduce anxiety without an overt sedative effect. Those medications that selectively produce antianxiety effects are discussed later in this chapter. 

Furthermore, the GABAa receptor is composed of several subunits (alpha, beta, gamma) it appears that individual subunits on this receptor mediate specific effects.3,11 Sedation, for example, seems to be mediated by the alpha 1 subunit, whereas other beneficial effects such as decreased anxiety might be mediated by the alpha 2 and alpha 3 subunits. Benzodiazepines seem to affect all of these subunits, hence their ability to produce sedative and antianxiety effects.3... 

Kava Piper methysticum Root of the kava plant Sedative-hypnotic and antianxiety effects... 

Kava originates from the root of the Piper methysticum (kava) plant that grows predominately in the South Pacific islands. This drug has been used for centuries by various local cultures because of its sedative and antianxiety effects. Kava has likewise gained popularity in western societies, and studies suggest that kava extracts can be used as an alternative to traditional sedative-hypnotic and anxiolytic drugs, such as benzodiazepines (see Chapter 6).21,39 Kava may also produce... 

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