Psychopharmacological Treatments

Several antidepressant medications and benzodiazepines have been found to be efficacious for panic treatment. Currently, selective serotonin reuptake inhibitors (SSRI's) are considered first-line treatment with regard to issues of safety and tolerability (APA, 1998). Paroxitene (Lydiard et al., 1998), fluvoxamine (Hoehn-Saric et al., 1993), fluox-itene (Michelson et al., 1998), sertraline (Rappaport et al., 1998), and citalopram (Wade et al., 1997) have all been found to be effective in placebo-controlled trials. Of these agents, paroxitene and sertraline are approved by the Food and Drug Administration (FDA) for the treatment of panic disorder. SSRIs were originally thought to have superior efficacy to tricyclic antidepressants, but treatment trials with larger numbers of subjects have suggested they are equivalent (Otto et al., 2001). Despite their overall tolerability, SSRIs may still have troubling side effects. These include sexual dysfunction, gastrointestinal symptoms (although these typically resolve), insomnia, and weight gain over time. Venlafaxine also shows promise for treatment of panic disorder (Pollack et al., 1996; Geracioti, 1995) but requires monitoring for blood pressure increases. Particularly important for panic patients, these medications can cause an initial increase in anxiety or agitation. Therefore, it is usually advisable to start these medications at lower doses than in major depression and to increase as tolerated. Benzodiazepines can aid in diminishing this agitation, which usually resolves within 1 to 2 weeks. Finally, following discontinuation of the medication, patients can struggle with a withdrawal syndrome, which includes dizziness, irritability, headache, nausea, and sometimes anxiety (Lejoyeux and Ades, 1997). This typically resolves within 2 weeks and can usually be eased with a slower taper of medication.

Although clomipramine, imipramine, and desipramine have shown efficacy in comparison with placebo (Lydiard, 1987; Uhlenhuth et al., 1989; Mavissakalian and Perel, 1995; Lecrubier et al., 1997; Fallon and Klein, 1997), they all have significant side effects, high rates of intolerance, and safety concerns (Noyes et al., 1989; Papp et al., 1997). These include anticholinergic side effects (dry mouth, constipation, difficulty urinating, blurred vision), sedation, orthostatic hypotension, weight gain, and sexual dysfunction. These agents can prolong cardiac conduction and in overdose or in patients with preexisting cardiac conduction defects, a fatal arrhythmia may occur. Clinical experience suggests that although monoamine oxidase inhibitors (MAOIs) are effective in treating panic, the dietary restrictions and the risks of serious side effects (potential hypertensive reaction, along with weight gain and orthostasis), greatly limit the usefulness of these agents. Some clinicians believe that MAOI's are superior to tricyclics for panic, but there is limited systematic data to support this notion, particularly given that most MAOI studies were done before the DSM III criteria for panic disorder were developed (Sheehan et al., 1980).

Benzodiazepines remain an important class of medications for treatment of panic disorder, despite their replacement as first-line agents by antidepressants. In clinical practice, these medications can provide rapid relief of panic attacks, allowing symptom reduction while other treatments, such as antidepressants or psychotherapy, are being introduced. An important limitation to the use of benzodiazepines is their lack of impact on depression or other commonly coexisting psychiatric conditions, such as agoraphobia, specific phobias, or obsessive-compulsive disorder. Side effects include sedation, fatigue, and memory impairment. Although these medications carry a potential risk of abuse, the risk is felt to be overestimated in patients with anxiety disorders (Uhlenhuth, et al., 1989). Avoidance of these medications out of fear of abuse may be more problematic than the risk of abuse. If benzodiazepines are employed over an extended period of time, patients are at risk for recurrence of symptoms when they are tapered. A more rapid taper or abrupt discontinuation or tapering of a shorter acting benzodiazepine increases the risk of symptom resurgence. Thus, a taper is best accomplished over 3 to 6 months, with a reduction in the rate of taper after the dose has reached half its original level.

More recent data suggests that some of the anticonvulsants may be effective in treating panic disorder. The potential efficacy of valproate has been indicated in two studies (Lum et al., 1990; Woodman and Noyes, 1994). Valproate is generally a well-tolerated agent but requires monitoring of hepatic enzymes, and there are rare reports of pancreatitis. Weight gain is also a potential side effect.

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