Treatment of Anxiety Disorders

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The anxiety disorders are treated with some form of counseling or psychotherapy or pharmacotherapy, either singly or in combination (Barlow & Lehman, 1996; March et al., 1997; American Psychiatric Association, 1998; Kent et al., 1998).

Counseling and Psychotherapy

Anxiety disorders are responsive to counseling and to a wide variety of psychotherapies. More severe and persistent anxiety symptoms also may require pharmacotherapy (American Psychiatric Association, 1998).

During the past several decades, there has been increasing enthusiasm for more focused, time-limited therapies that address ways of coping with anxiety symptoms more directly rather than exploring unconscious conflicts or other personal vulnerabilities (Barlow & Lehman, 1996). These therapies typically emphasize cognitive and behavioral assessment and interventions.

The hallmarks of cognitive-behavioral therapies are evaluating apparent cause and effect relationships between thoughts, feelings, and behaviors, as well as implementing relatively straightforward strategies to lessen symptoms and reduce avoidant behavior (Barlow, 1988). A critical element of therapy is to increase exposure to the stimuli or situations that provoke anxiety. Without such therapeutic assistance, the sufferer typically withdraws from anxiety-inducing situations, inadvertently reinforcing avoidant or escape behavior.

The therapist provides reassurance that the feared situation is not deadly and introduces a plan to enhance mastery. This plan may include approaching the feared situation in a graduated or stepwise hierarchy or teaching the patient to use responses that dampen anxiety, such as deep muscle relaxation or coping. One fundamental principle is that prolonged exposure to a feared stimulus reliably decreases cognitive and physiologic symptoms of anxiety (Marks, 1969; Barlow, 1988). With such experience generally comes greater self-efficacy and a greater willingness to encounter other feared stimuli. For panic disorder, interoceptive training (a type of conditioning technique) and breathing exercises are often employed to help the sufferer become more capable of recognizing and coping with the social cues, antecedents, or early signs of a panic attack. Cognitive interventions are used to counteract the exaggerated or catastrophic thoughts that characterize anxiety. For treatment of obsessive-compulsive disorder, the strategy of response prevention must be added to exposure to ensure that compulsions are not performed (Barlow, 1988).

There is now extensive evidence that cognitive-behavioral therapies are useful treatments for a majority of patients with anxiety disorders (Chambless et al., 1998). Poorer outcomes are observed, however, in more complicated patient groups. With obsessive-compulsive disorder, approximately 20 to 25 percent of patients are unwilling to participate in therapy (March et al., 1997). Another major limitation of cognitive-behavioral therapies is not their effectiveness but, rather, the limited availability of skilled practitioners (Ballenger et al., 1998).

It is possible that more traditional forms of therapy based on psychodynamic or interpersonal theories of anxiety also may prove to be effective treatments (Shear, 1995). However, these therapies have not yet received extensive empirical support. As a result, more traditional therapies are generally deemphasized in evidence-based treatment guidelines for anxiety disorders.

Pharmacotherapy

The medications used to treat patients with anxiety disorders are benzodiazepines, antidepressants, and the novel compound buspirone (BuSpar)(Lydiard et al., 1996). In light of increasing awareness of numerous neurochemical alterations in anxiety disorders, many new classes of drugs are likely to be developed, expressly targeting CRH and other neuroactive agents (Nemeroff, 1998).

Benzodiazepines
The benzodiazepines are a large class of relatively safe and widely prescribed medications that have rapid and profound antianxiety and sedative-hypnotic effects. The benzodiazepines are thought to exert their therapeutic effects by enhancing the inhibitory neurotransmitter systems utilizing GABA. Benzodiazepines bind to a site on the GABA receptor and act as receptor agonists (Perry et al., 1997). Benzodiazepines differ in terms of potency, pharmacokinetics (i.e., elimination half-life), and lipid solubility.

The four benzodiazepines currently widely prescribed for treatment of anxiety disorders are diazepam, lorazepam, clonazepam, and alprazolam. Each is now available in generic formulations (Davidson, 1998). Among these agents, alprazolam and lorazepam have shorter elimination half-livesthat is, are removed from the body more quicklywhile diazepam and clonazepam have a long period of action (i.e., up to 24 hours). Diazepam also has multiple active metabolites, which increase the risk of carryover effects such as sedation and hangover. Benzodiazepines that undergo conjugation appear to have longer elimination time in women, and oral contraceptive can decrease clearance (Dawlans, 1995). Since Asians are more likely to metabolize diazepam more slowly, they may require lower doses to achieve the same blood concentrations as Caucasians (Lin et al., 1997).

Benzodiazepines have the potential for producing drug dependence (i.e., physiological or behavioral symptoms after discontinuation of use). Shorter acting compounds have somewhat greater liability because of more rapid and abrupt onset of withdrawal symptoms.

Because the benzodiazepines do not have strong antiobsessional effects, their use in obsessive-compulsive disorder and post-traumatic stress disorder is generally viewed as palliative (i.e., relieving, but not eliminating symptoms). Rather, obsessive-compulsive disorder and post-traumatic stress disorder are more effectively treated by antidepressants, especially the SSRIs (as discussed below). When effective, benzodiazepines should be tapered after several months of use, although there is a substantial risk of relapse. Many clinicians favor a combined treatment approach for panic disorder and generalized anxiety disorder, in which benzodiazepines are used acutely in tandem with an antidepressant. The benzodiazepines are subsequently tapered as the antidepressants therapeutic effects begin to emerge (American Psychiatric Association, 1998).

Antidepressants
Most antidepressant medications have substantial antianxiety and antipanic effects in addition to their antidepressant action (Kent et al., 1998). Moreover, a large number of antidepressants have antiobsessional effects (Perry et al., 1997). The observation that the tricyclic antidepressant imipramine had a different anxiolytic profile than diazepam helped to differentiate panic disorder from generalized anxiety disorder and, subsequently, social phobia.

Clomipramine, a tricyclic antidepressant (TCA) with relatively potent reuptake inhibitory effects on serotonin (5-HT) neurons, subsequently was found to be the only TCA to have specific antiobsessional effects (March et al., 1997). The importance of this effect on 5-HT was highlighted when the SSRIs became available. By the late 1990s, it became clear that all of the SSRIs have antiobsessional effects (Greist et al., 1995; Kent et al., 1998).

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Current practice guidelines rank the TCAs below the SSRIs for treatment of anxiety disorders because of the SSRIs more favorable tolerability and safety profiles (March et al., 1997; American Psychiatric Association, 1998; Ballenger et al., 1998). Nevertheless, there are patients who respond to the TCAs after failing to respond to one or more of the newer agents. Similarly, although relatively rarely used, the monoamine oxidate inhibitors (MAOIs) have significant antiobsessional, antipanic, and anxiolytic effects (Sheehan et al., 1980; American Psychiatric Association, 1998). In the United States, the MAOIs phenelzine, tranylcypromine, and isocarboxazid (which has not been consistently marketed this decade) are seldom used unless simpler medication strategies have failed (American Psychiatric Association, 1998).

The five drugs within the SSRI class - fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram - have emerged as the preferred type of antidepressant for treatment of anxiety disorders (Westenberg, 1996; Kent et al., 1998). In addition to well-established efficacy in obsessive-compulsive disorder, there is convincing and growing evidence of antipanic and broader anxiolytic effects (American Psychiatric Association, 1998; Kent et al., 1998). Treatment of panic disorder often requires lower initial doses and slower upward titration. By contrast, treatment for obsessive-compulsive disorder ultimately may entail higher doses (for example, 60 or 80 mg/day of fluoxetine or 200 mg per day of sertraline) and longer durations to achieve desired outcomes (March et al., 1997). As all of the SSRIs are currently protected by patents, there are no generic forms yet available. This adds to the direct costs of treatment. Cost may be offset indirectly, however, by virtue of need for fewer treatment visits and fewer concomitant medications, and cost likely will abate when these agents begin to lose patent protection in a few years.

Other newer antidepressants, including venlafaxine, nefazodone, and mirtazapine, also may have significant antianxiety effects, for which clinical trials are under way (March et al., 1997; American Psychiatric Association, 1998). Paroxetine has been approved by the Food and Drug Administration (FDA) for social phobia, and sertraline is being developed for post-traumatic stress disorder. Nefazodone, which also is being studied in post-traumatic stress disorder, and mirtazapine may possess lower levels of sexual side effects, a problem that complicates longer term treatment with SSRIs, venlafaxine, TCAs, and MAOIs (Baldwin & Birtwistle, 1998).

When effective in treating anxiety, antidepressants should be maintained for at least 4 to 6 months, then tapered slowly to avoid discontinuation-emergent activation of anxiety symptoms (March et al., 1997; American Psychiatric Association, 1998; Ballenger et al., 1998). Although less extensively researched than depression, it is likely that many patients with anxiety disorders may warrant longer term, indefinite treatment to prevent relapse or chronicity.

Buspirone
This azopyrine compound is a relatively selective 5- HT_1A partial agonist (Stahl, 1996). It was approved by the FDA in the mid-1980s as an anxiolytic. However, unlike the benzodiazepines, buspirone is not habit forming and has no abuse potential. Buspirone also has a safety profile comparable to the SSRIs, and it is significantly better tolerated than the TCAs.

Buspirone does not block panic attacks, and it is not efficacious as a primary treatment of obsessive-compulsive disorder or post-traumatic stress disorder (Stahl, 1996). Buspirone is most useful for treatment of generalized anxiety disorder, and it is now frequently used as an adjunct to SSRIs (Lydiard et al., 1996). Buspirone takes 4 to 6 weeks to exert therapeutic effects, like antidepressants, and it has little value for patients when taken on an as needed basis.

Combinations of Psychotherapy and Pharmacotherapy
Some patients with anxiety disorders may benefit from both psychotherapy and pharmacotherapy treatment modalities, either combined or used in sequence (March et al., 1997; American Psychiatric Association, 1998). Drawing from the experiences of depression researchers, it seems likely that such combinations are not uniformly necessary and are probably more cost-effective when reserved for patients with more complex, complicated, severe, or comorbid disorders. The benefits of multimodal therapies for anxiety need further study.

Source: Mental Health: A Report of the Surgeon General - Chapter 4