Obsessive-compulsive disorder anxiolytics

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. 

The efficacy of benzodiazepines in most anxiety disorders has been proved through extensive clinical experience and controlled trials (Faravelli et al. 2003), although it is important to note that they are not effective at treatingpost-traumatic stress disorder or comorbid depression, and there is less evidence to support their use in obsessive-compulsive disorder (OCD). Their anxiolytic effects have an immediate onset and in contrast to many other drugs, they do not cause a worsening of anxiety when therapy is initiated. 

Mechanism of Action An antidepressant, anxiolytic, and obsessive-compulsive disorder adjunct that blocks the reuptake of the neurotransmitter serotonin at CNS neuronal presynaptic membranes, Increasing its availability at postsynaptic receptor sites. Therapeutic Effect Relieves depression, reduces obsessive-compulsive behavior, decreases anxiety... 

The anxiolytic activity of several compounds in some, but not all, animal models of anxiety in fact suggests that different receptor subtypes may modulate different types of anxiety as discussed below. It would not be surprising if the specific serotonin links to disorders of anxiety also differ among the various disorders of anxiety such as generalized anxiety versus obsessive-compulsive disorder versus panic disorder versus social phobia versus mixed anxiety depression. Such studies are in progress, and much further research is necessary to clarify the potential links between subtypes of anxiety and subtypes of serotonin receptors. 

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... 

By the 1990s antidepressants from the serotonin selective reuptake inhibitor (SSRI) class became recognized as preferred first-line treatments for anxiety disorder subtypes, ranging from obsessive-compulsive disorder, to panic disorder, and now to social phobia and posttraumatic stress disorder (Fig. 8—9). Not all antidepressants, however, are afficacious anxiolytics. For example, desipramine and bupropion seem to be of little help in several anxiety disorder subtypes. Documentation of efficacy... 

It will be noted (Table 12-17) that these four first-generation TCAs are tertiary amines. Their clinical activity was initially described as neuroleptic (mood elevating). They also exhibited a degree of anxiolytic effects and reduced agitation in animals and humans. The introduction of clomipramine (2-chloroimipramine) (1990) offered the psychiatrist the first drug effectively to treat obsessive-compulsive disorders of the type serious enough to interfere with social or occupational functions. 

Psychiatrists prescribe antipsychotics to treat mental illnesses that cause patients to experience marked breaks with reality (psychosis). The most common of such disorders is schizophrenia, which is a chronic, disabling, persistent, and severe brain disease that sigpiificantly impairs brain functioning and affects 1 percent of the world s population, including 3 million people in the United States alone. Antipsychotic medications are referred to as typical or atypical. Psychiatrists prescribe anxiolytics (antianxiety medications) to treat anxiety disorders, which include panic disorder, generalized anxiety disorder, specific phobias, obsessive-compulsive disorder, social anxiety disorder, and posttraumatic stress disorder. Psychiatrists prescribe antidepressants and mood stabilizers to treat the symptoms of mood disorders, the most common and severe of which are major depression and bipolar disorder. 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

---