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As many as 70% of patients with panic disorder fulfill the diagnostic criteria for major depression at some point in their lives.

Epidemiology and Clinical Features

Panic disorder is one of the primary anxiety disorders described in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association. It is a chronic disorder with a lifetime prevalence estimated to be between 1.5% and 3.5% and an onset generally in early adulthood. It is characterized by the occurrence of recurrent, unexpected panic attacks followed by at least one month of persistent concern about experiencing further attacks, worry about the consequences of the attacks, or a significant change in behavior secondary to the attacks. The attacks may last seconds to minutes and are characterized by dyspnea, palpitations, tremulousness, dizziness, hot and cold flashes, diaphoresis, chest pain, feelings of unreality, numbness or tingling, faintness, fear of going crazy, and fear of dying (see Table 1). These attacks are extremely frightening and disabling; many of these patients are seen in the medical emergency room because they think they are having a heart attack. If a sufficient number of panic attacks occur, patients may develop anticipatory anxiety (i.e., anxiety associated with the fear of the next occurrence) as well as avoidant behavior. When this avoidant behavior severely restricts the daily activity of the individual (i.e., avoiding public places and/or leaving home for fear of having a panic attack during which help will not be available), the diagnosis of panic disorder with agoraphobia is made. Up to 70% of patients with panic disorder fulfill the diagnostic criteria for major depression at some point in their lives.

Traditional Treatments

Until recently, primarily three drugs have been used in the pharmacotherapy of panic disorder: the tricyclic antidepressant imipramine; the monoamine oxidase inhibitor phenelzine; and the benzodiazepine alprazolam. Among the three, only alprazolam has an FDA approved indication for the treatment of panic disorder; however, all three have demonstrated efficacy. Often, imipramine would be selected for patients with concomitant depression and avoided in patients who could not tolerate the sedative, anticholinergic, hypotensive, or cardiac conduction adverse effects. Phenelzine may have an advantage in patients with significant phobic avoidance; however, it is commonly reserved as a last resort due to fear over drug-drug and drug-food interactions resulting in possible hypertensive crises. Alprazolam would be given to patients with significant anticipatory anxiety, as well as those who could not tolerate imipramine, and avoided in patients who would be adversely affected by the drug’s tendency to produce sedation and psychomotor impairment. In addition, most prescribers would avoid use of this agent in any patients with a history of alcohol or substance abuse due to its abuse potential. More recently, clonazepam was approved by the FDA for the treatment of panic disorder. Compared with alprazolam, it has the advantage of a longer half-life of elimination, reducing the frequency of dosing as well as the inter-dose rebound anxiety sometimes seen with alprazolam.