Anxiolytics, other Antidepressant

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

The SSRls as a class are now widely considered to be appropriate first-line anxiolytic drugs in particular paroxetine, the most potent 5-HT reuptake blocker, has been licensed in the UK for the treatment of each of the major anxiety disorders. Short-term efficacy has been clearly demonstrated in randomised controlled trials, but in common with other antidepressants, research evidence is lacking for long-term efficacy and necessary duration of treatment. 

Buspirone. Hie initial compound in this series, buspir-one (BuSpar). has anxiolytic and antidepre.ssnnt activities and is a partial. iHTiA agonist. Its anxiolytic activity is reportedly due to its ability to diminish. -ITT release (via. SHTia agonism). High short-term synaptic levels of. S-HT ate characteri.stic of anxiety. Also, since it is a partial agoni.st. it can stimulate postsynaptie receptors when 5-HT levels are low in the synapse, as is the case in depression. A number of other spirones are in development as anxiolytics and antidepressants. ... 

Doxepin [1668-19-5] (38), unlike other commercially available tricyclics, has an oxygen atom in the bridge between the two aromatic rings. It is marketed as a cis—trans mixture (1 5) of isomers, both of which are active. This close relative of amitriptyline (33) has both sedative and anxiolytic properties associated with its antidepressant profile. Maprotiline [10262-69-8] (39) and amoxapine [14028-44-5] (40) are pharmacologically, although not chemically, similar to the tricycHc secondary amines. Clomipramine [303-49-1] (41) has similar pharmacological and antidepressant efficacy. However, clomipramine is approved by the U.S. FDA only for the treatment of obsessive—compulsive disorder. Representative brands of tricycHc antidepressants marketed in the United States are Hsted in Table 2. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

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. 

Equally effective as other tricyclic antidepressants for depression distinguishing characteristics include sedative, anxiolytic, antihistaminic properties... 

SRls have proven to be effective in OCD both with and without depression. Other treatment modalities, such as nonserotonergic antidepressants or anxiolytics, do not appear to be consistently effective. Despite the impressive progress achieved in the clinical management of OCD, several issues await clarification, such as the length of maintenance therapy, the role of behavioral therapy and pharmacological therapy alone and in combination, and the approach to patients who are nonresponsive to treatment. Also, further research is needed to differentiate nonresponsive patients into various subgroups and apply specific techniques for each group. 

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