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).

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

next: Panic Attack and Agoraphobia