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1. Panic Disorder: Three Stages of Development

Panic disorder is a subtype of anxiety manifested by discrete periods of apprehension or fear and at least four specific somatic symptoms (see exhibit 1). To meet DSM-III-R criteria (APA 1987), at least some of these attacks must be spontaneous and appear unexpectedly when the patient is not exposed to a phobic stimulus or in a situation in which the person is the focus of others’ attention. At least four of these anxiety attacks must occur within a 4-week period, or one or more of the attacks must be followed by a period of at least a month of persistent fear of having another attack.

Although patients subjectively feel short of breath or as if they are smothering, often they are actually hyperventilating. In fact, carbon dioxide, bicarbonate, and phosphorous levels have all been found to be lower in patients with panic attacks than in controls (Gorman et al. 1988a). This evidence suggests chronic hyperventilation, for although carbon dioxide levels change rapidly, changes in bicarbonate take longer to develop and are likely to be secondary to renal compensation for respiratory alkalosis (Stanburg and Thompson 1952). This may be a key factor in the chronicity and ready provocation of symptoms associated with hyperventilation and anxiety attacks in these individuals. Chronic hypocapneia may cause symptoms to be present much of the time, and minimal reductions of an already lowered pC02 may precipitate acute symptoms (Magarian 1982).

Patients with evidence of chronic hyperventilation often can be diagnosed by their occasional sighing or deep respirations during the medical interview. Respiratory physiologists have determined that just an occasional sigh or deep respiration is enough to maintain hypocapneic respiratory alkalosis (Magarian 1982). Signs and symptoms of hyperventilation disappear with effective pharmacologic or behavioral treatment of panic disorder. In most cases, hyperventilation is probably not the cause of panic disorder but simply an epiphenomenon of this severe anxiety disorder.

Chronologically, panic disorder develops in three separate stages, with patients potentially stopping at any stage or progressing through all three (exhibit 2). Patients will often have their first attack or cluster of attacks after a variety of life stresses. Patients will usually describe this acute attack as extremely frightening and, at times, the worst experience of their lives. These first attacks typically occur suddenly and unexpectedly while the patients are performing everyday tasks (driving in a car, walking to work). Suddenly, they may experience rapid heartbeat, dyspnea, dizziness, chest pain, nausea or abdominal distress, numbness or tingling of hands and feet, depersonalization or derealization, trembling or shaking, sweating, choking, or a feeling that they are going to lie, go crazy, or do something uncontrolled.

Exhibit 1. Diagnostic criteria for panic disorder
A At some time during the disturbance, one or more panic attacks (discrete periods of intense fear or discomfort) have occurred that were (1) unexpected, i.e., did not occur immediately before or on exposure to a situation that almost always caused anxiety and (2) not triggered by situations in which the person was the focus of others' attention.
B Either four attacks, as defined in criterion A, have occurred within a 4-week period, or one or more attacks have been followed by a period of at least a month of persistent fear of having another attack.
C At least four1of the following symptoms developed during at least one of the attacks:
  1. shortness of breath (dyspnea) or smothering sensations
  2. dizziness, unsteady feelings, or (aintness
  3. palpitations or accelerated heart rate (tachycardia)
  4. trembling or shaking
  5. sweating
  6. choking
  7. nausea or abdominal distress
  8. depersonalization or derealization2
  9. numbness or tingling sensations (paresthesias)
  10. flushes (hot flashes) or chills
  11. chest pain or discomfort
  12. fear of dying
  13. fear of going crazy or of doing something uncontrolled
D During at least some of the attacks, at least four of the C symptoms developed suddenly and increased in intensity within 10 minutes of the beginning of the first C symptom noticed in the attack.
E It cannot be established that an organic factor initiated and maintained the disturbance, e.g., amphetamine or caffeine intoxication, hyper-thyroidism.3
Source: Reprinted with permission from the Diagnostic and Statistical Manual of Mental . Disorders. Third Edition, Revised. Copyright 1987 American Psychiatric Association, p. 237-238.
  1. Attacks involving four or more symptoms are panic attacks; attacks involving fewer than four symptoms are limited symptom attacks.
  2. Depersonalization is manifested by a feeling of detachment from and being an outside observer of one's body or mental processes, or of feeling like an automaton or as if in a dream. Derealization is evidenced by a strange alteration in the perception of one's surroundings so that a sense of the reality of the external world is lost. Alteration in the size or shape of objects in the external world is commonly perceived.
  3. Mitral valve prolapse may be an associated condition, but does not preclude a diagnosis of panic disorder.

Exhibit 2. Three stages in development of panic disorder
Initial acute panic attack or cluster of attacks Panic attacks increase in frequency.
Phobias develop
Anticipatory anxiety and avoidance behaviors develop
Medical care-seeking dramatically increases for somatic complaints		 Agoraphobia dependency.
Dramatic changes in family system
Chronic somatization develops

Primary care physicians may see patients after their first few attacks. The presenting symptom of these patients is often the single most frightening autonomic sensation, such as chest pain or dizziness, and they are convinced that something is deadfully wrong with their body.

Not all patients go on to develop chronic symptoms of panic disorder Katon et al. 1987a). A subgroup of patients will develop one or more attacks under stress, but with reassurance and education about the nature of their attacks and supportive therapy by their primary care physician will not develop incapacitating panic disorder. Many people may experience occasional attacks, but the diagnosis of panic disorder is reserved for those whose attacks occur with some regularity and frequency or where strong anticipatory anxiety develops after a small number of attacks (Hollander et al. 1988).

Norton and colleagues (1985) found that 34 percent of college students had suffered infrequent panic attacks, but only 2.2 percent met DSM-III criteria for panic disorder. Another study (Katon et al. 1987a) found that while 20 percent f primary care patients had met criteria for panic disorder at some time in their lives, another 18.4 percent had infrequent attacks and never met criteria for panic disorder. The patients with infrequent attacks had significantly higher sores on measures of anxiety and depression compared to controls. They may represent a population at high risk for the development of panic disorder and major depression when stressful life events occur (Brown et al. 1986).

Many patients move quickly to the second stage in which the anxiety attacks become increasingly frequent and severe and the patient develops anticipatory anxiety — fear of having a panic attack. During this second phase, events and circumstances associated with the attacks may be selectively avoided, leading to phobic behaviors. For example, a man who has an anxiety attack on a bus may become quite anxious the next time he has to take a bus (anticipatory anxiety) and may begin avoiding public transportation (bus phobia). In this phase, patients' lives may become progressively constricted so that they avoid even activities and places in which they previously felt quite comfortable.

In a prevalence study of panic disorder in primary care, patients with panic disorder averaged 4.8 phobias compared to 1.2 phobias in controls who had never experienced a panic attack (Katon et al. 1986). The patients with panic attacks tended to have multiple social phobias (fear of eating in public, crowds, speaking to a small group of people, speaking to strangers) as well as fear of situations where they feel trapped (elevators, public transportation, driving on bridges or freeways). Katon and colleagues (1986) also found that not all patients with panic disorder developed avoidance behavior and phobias after developing panic attacks, although almost all reported increased social anxiety subsequent to the development of panic disorder.

Vitaliano et al. (1987) studied patients' coping patterns in dealing with stress by a standardized coping questionnaire, The Ways of Coping Checklist (Vitaliano et al. 1985). This questionnaire evaluates the patient's tendency to use several coping mechanisms including Problem-Focused Coping, Wishful Thinking, Avoidance, Seeks Social Support, and Blames Self. The study determined that the way patients with panic disorder characteristically coped with stressful life events was a better predictor of whether the patient developed multiple phobias than the severity of their anxiety and depression (Vitaliano et al. 1987). This suggests that personality variables such as coping are intimately associated with the level of social disability the patient develops secondary to panic attacks.

During this second stage of panic disorder, patients often dramatically increase their use of health services, going from physician to physician with one or more frightening somatic complaints (Katon 1984). They frequently become quite hypochondriacal and focus on their bodies with anxiety and fear that they have a life-threatening medical illness. The types of symptoms they present with can be cues to the physician that the patient may have panic disorder. These are reviewed in the chapter on somatization.. Accurate diagnosis and treatment are quite important in this second stage, for patients may develop multiple phobias and anticipatory anxiety that can cripple their social and vocational lives.

Overlapping with the second stage of limited phobic avoidance, a third stage may develop in which the patient acquires more extensive avoidance behavior and becomes agoraphobic. "Agora" means marketplace in Greek and agoraphobia literally means fear of the marketplace. In DSM-III-R (APA 1987), agoraphobia refers to a fear of being in places or situations from which escape might be difficult or embarrassing or help might be unavailable in the event of a panic attack.

The DSM-III-R criteria for panic disorder with agoraphobia cover stages two and three of panic disorder (see exhibit 3). Thus, DSM-III-R lists the current severity of agoraphobia in stages between mild and severe, recognizing that some patients have only mild avoidance while others become homebound or unable to leave the house unaccompanied by a significant other.

Primary care physicians should ask whether the patient has begun to avoid any situations, especially social situations, since the attacks began. If the patient answers no to this question, specific inquiries about fear of crowds, public transportation, closed in spaces (elevators, movie theaters, church), driving alone, and going out socially with friends are important diagnostic questions. It is essential to inquire whether the patient has become fearful of entering these situations alone, since many agoraphobic patients will enter fearful situations when accompanied by a spouse or significant other. One useful question is "Since these episodes or attacks started, if you went to a crowded movie theater alone (if they never go to movies, ask about church) and every seat was taken but you had a choice of any seat, where would you sit?" About 80 percent of the time, the patient will state "An aisle seat in the last row or near an exit." This question reflects the tendency for the patient with panic disorder to become afraid of being in places or situations where escape might be difficult or highly embarrassing in the event of a panic attack.

As the agoraphobia worsens (third stage of panic disorder), patients become increasingly dependent on their spouses, demanding that they accompany them when they have to leave home or enter social situations. Dramatic changes may occur in the family system, with both the spouse and children affected adversely by the patient's dependency, avoidance of social situations, and clingy behavior. The spouse and children may be forced to take over many of the patient's responsibilities, such as shopping, earning wages, and attending school meetings. The patient's vocation may be adversely affected by absenteeism and avoidance of social situations at work, e.g., business lunches, making new client contacts, giving oral presentations.

In this third stage of panic disorder, patients frequently visit their physicians regularly and are often reassured "it's just your nerves" or "stress is causing your symptoms." Thompson and colleagues (1988) have shown that agoraphobia is the most common phobia leading to use of health services, especially when it is accompanied by panic attacks. Several studies have demonstrated that most patients view fear and anxiety as late symptoms of panic attacks that result from the frightening autonomic symptoms (Katerndahl 1988; Ley 1985). Thus, many patients view their symptoms of nervousness and anxiety as appropriate responses to severe physiologic sensations. These patients are especially likely to present with concern about one or more autonomic symptoms associated with panic disorder, such as tachycardia, chest pain, or dyspnea, and to answer physician queries about nervousness or anxiety with statements such as "Anyone with the physical symptoms I'm having (chest pain, dyspnea, dizziness) would be frightened" (Katon 1988).

Exhibit 3. Diagnostic criteria for panic disorder with agoraphobia
A Meets the criteria for panic disorder.
B Agoraphobia: Fear of being in places or situations from which escape might be difficult (or embarrassing) or in which help might not be available in the event of a panic attack. (Include cases in which persistent avoidance behavior originated during an active phase of panic disorder, even if the person does not attribute the avoidance behavior to fear of having a panic attack.) As a result of this fear, the person either restricts travel or needs a companion when away from home, or else endures agoraphobic situations despite intense anxiety. Common agoraphobic situations include being outside the home alone, being in a crowd or standing in a line, being on a bridge, and traveling in a bus, train, or car.
Specify current severity of agoraphobic avoidance:
Mild: Some avoidance (or endurance with distress), but relatively normal lifestyle, e.g., travels unaccompanied when necessary, such as to work or to shop; otherwise avoids traveling alone.
Moderate: Avoidance results in constricted lifestyle, e.g., the person is able to leave the house alone, but not to go more than a few miles unaccompanied.
Severe: Avoidance results in being nearly or completely housebound or unable to leave the house unaccompanied.
In partial remission: No current agoraphobic avoidance, but some agoraphobic avoidance during the past 6 months.
In full remission: No current agoraphobic avoidance and none during the past 6 months.
   
Specify current severity of panic attacks:
Mild: During the past month, either all attacks have been limited symptom attacks (i.e., fewer than four symptoms), or there has been no more than one panic attack.
Moderate: During the past month, attacks have been intermediate between "Mild" and "Severe."
Severe: During the past month, there have been at least eight panic attacks.
In partial remission: The condition has been intermediate between "In full remission" and "Mild."
In full remission: During the past 6 months, there has been no panic or limited remission: symptom attack.
Source: Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders. Third Edition, Revised. Copyright 1987 American Psychiatric Association, p. 238-239.

During a study on the prevalence of panic disorder in primary care, Katon et al. (1987a) found that a positive response to the one screening question in the structured psychiatric interview— "Have you ever had a spell or attack when all of a sudden you felt frightened, anxious, or very uneasy in situations when most people would not be afraid?" — often did not accurately identify a substantial subset of patients with panic disorder. These patients were accurately identified by adding several somatic questions, the most sensitive being "Do you ever have sudden episodes of rapid heartbeat or palpitations?" The patients accurately screened by the somatic questions perceived that their anxiety was appropriate to the severity of their somatic symptoms. The patients identified by the somatic screening questions had significantly higher scores on measures of anxiety, depression, and somatization than did control patients without panic disorder.

Primary care physicians frequently see patients with panic disorder at an early stage in their illness. Accurate diagnosis and appropriate treatment at this stage can decrease hypochondriasis and high medical utilization as well as prevent disruption of vocational and social roles.