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Though panic disorder and panic disorder with agoraphobia or phobic avoidance (PDA) are common (the mean lifetime prevalence of panic disorder is 1.5%), the diagnosis is frequently missed: 70% of patients with PDA in one large study had more than ten medical consultations before receiving the correct diagnosis and treatment.

The “classic” presentation of panic disorder consists of sudden, unexpected, discrete attacks of intense fear or discomfort without a recognizable precipitant, accompanied by at least four of the following symptoms during at least one of the attacks: dyspnea or smothering sensations; dizziness, unsteadiness, or faintness; palpitations or tachycardia; trembling or shaking; sweating; choking; nausea or abdominal distress; depersonalization or derealization; numbness or paresthesias; flushes or chills; chest pain or discomfort; fear of dying; and fear of going crazy or doing something uncontrolled. Panic disorder, however, frequently occurs with symptoms referable to only a single organ system. Such single system presentations include chest pain and dyspnea (33% to 59% of patients seen because of chest pain but with no abnormalities found on coronary angiography were found in three different studies to have PDA); balance disorder (“dizziness”) without true vertigo (25% to 50% of patients seen because of vestibular disorder symptoms have a subtype of panic disorder); abdominal discomfort, pain, and diarrhea (about 33% of patients seen by gastroenterologists were found to have PDA).

Large-scale clinical studies have shown that for most patients, PDA is a chronic relapsing disorder. Multiple family and twin studies show that panic disorder has a highly familial transmission with a strong genetic component (31% monozygotic concordance, 0% dizygotic concordance).

Panic disorder with agoraphobia has a startlingly high comorbidity and mortality. Patients with untreated PDA attempt suicide at a rate equivalent to that of patients with major depression (15% to 20% of patients). This disorder has a dramatically high incidence of comorbid major depression, alcohol abuse, substance abuse, other anxiety disorders, multiple phobias or agoraphobia, cardiovascular disease, and personality disorders. Patients with PDA experience substantially more impairment in social, family, and occupational functioning than the general population.

The proven standard of effective treatment for PDA continues to be pharmacotherapy to stop and prevent recurrent panic attacks, plus behavior therapy (exposure in vivo) for any phobic avoidance that may remain once the panic attacks have been stopped. Most clinical studies have found the first-generation tricyclic antidepressants, the monoamine oxidase inhibitors, and two of the benzodiazepines (alprazolam [Xanax] and clonazepam [Klonopin]) highly effective in stopping and preventing recurrent panic attacks when maintained at therapeutic blood concentrations. Of the newer antidepressant medications, fluoxetine (Prozac) and clomipramine hydrochloride (Anafranil) have demonstrated efficacy in PDA, whereas buproprion hydrochloride (Wellbutrin) and the nonbenzodiazepine anxiolytic buspirone hydrochloride (BuSpar) have not.

The goal of appropriate pharmacologic management is the complete absence of all panic and subpanic attacks. This can be achieved with a single medication in more than 85% of patients, though it may take several treatment trials to find the best medication. Refractory cases may require more complicated protocols.

Recent reports of two nonpharmacologic treatments, cognitive therapy and cognitive-behavioral therapy, show promise for some patients with PDA.

The core of cognitive-behavioral treatment is systematic structured exposure to the feared internal sensations, coupled with cognitive procedures to restructure anxiety-provoking thoughts, catastrophic misinterpretations, and faulty core beliefs. The therapist directs the patient to induce the somatic sensations typical of a panic attack (dizziness, tachycardia, dyspnea, chest tension) in the office (by having the patient spin around, run in place, hyperventilate, or contract chest muscles tightly), while together therapist and patient critically examine the symptom experience, correct the patient’s frightening and catastrophic cognitive misinterpretations of the sensations, and control the symptoms with a variety of relaxation techniques. The patient practices at home what is learned in the office and keeps a daily diary of symptoms, reflex cognitive distortions, and corrective thinking and behavior.

Reports of the nonpharmacologic treatment of PDA to date review small treatment populations and short follow-up periods. The few studies comparing the efficacy (short- and long-term) of pharmacologic and nonpharmacologic treatments suffer from a variety of conceptual and methodologic difficulties. These include a failure to differentiate patients with panic disorder from those with panic disorder and agoraphobia or those with subtypes of panic disorder, and the heterogeneity of diagnostic criteria, treatment procedures, and measures of clinical success. Thus, our present state of knowledge does not enable us to predict accurately which patients will do best with which treatment(s) or how different treatments might best be integrated.

Patients with PDA should be educated regarding the various treatment options available. The choice of treatment will depend on the training and expertise of the clinician, the availability of specialists, a patient’s sense of urgency, available resources, and the preferred type of treatment. If nonpharmacologic treatment is elected, those patients who are not completely relieved of panic attacks after an adequate treatment trial (three months), or who relapse after treatment, should receive appropriate pharmacologic therapy for panic, combined with exposure treatment of phobic avoidance.