Diagnostic Features
The essential feature of Panic Disorder is the presence of recurrent, unexpected Panic Attacks followed by at least 1 month of persistent concern about having another Panic Attack, worry about the possible implications or consequences of the Panic Attacks, or a significant behavioral change related to the attacks (Criterion A). The Panic Attacks are not due to the direct physiological effects of a substance (e.g., Caffeine Intoxication) or a general medical condition (e.g., hyperthyroidism) (Criterion C). Finally, the Panic Attacks are not better accounted for by another mental disorder (e.g., Specific or Social Phobia, Obsessive-Compulsive Disorder, Posttraumatic Stress Disorder, or Separation Anxiety Disorder) (Criterion D). Depending on whether criteria are also met for Agoraphobia, Panic Disorder With Agoraphobia or Panic Disorder Without Agoraphobia is diagnosed (Criterion B).

An unexpected (spontaneous, uncued) Panic Attack is defined as one that an individual does not immediately associate with a situational trigger (i.e., it is perceived as occurring “out of the blue”). Situational triggers can include stimuli that are either external (e.g., a phobic object or situation) or internal (e.g., physiological arousal) to the individual. In some instances, although a situational trigger may be apparent to the clinician, it may not be readily identifiable to the individual experiencing the Panic Attack.

For example, an individual may not immediately identify increased autonomic arousal induced by a hot, stuffy room, or feelings of faintness produced by quickly sitting up as triggers for a Panic Attack, and as such, these attacks are considered at the time to be unexpected. At least two unexpected Panic Attacks are required for the diagnosis, but most individuals have considerably more. Individuals with Panic Disorder frequently also have situationally predisposed Panic Attacks (i.e., those more likely to occur on, but not invariably associated with, exposure to a situational trigger). Situationally bound attacks (i.e., those that occur almost invariably and immediately on exposure to a situational trigger) can occur but are less common.

The frequency and severity of the Panic Attacks vary widely. For example, some individuals have moderately frequent attacks (e.g., once a week) that occur regularly for months at a time. Others report short bursts of more frequent attacks (e.g., daily for a week) separated by weeks or months without any attacks or with less frequent attacks (e.g., two each month) over many years. Limited-symptom attacks (i.e., attacks that are identical to “full” Panic Attacks except that the sudden fear or anxiety is accompanied by fewer than 4 of the 13 symptoms) are very common in individuals with Panic Disorder. Although the distinction between full Panic Attacks and limited-symptom attacks is somewhat arbitrary, full Panic Attacks are typically associated with greater morbidity (e.g., greater health care utilization, greater functional impairment, poorer quality of life). Most individuals who have limited-symptom attacks have had full Panic Attacks at some time during the course of the disorder.

Individuals with Panic Disorder display characteristic concerns or attributions about the implications or consequences of the Panic Attacks. Some fear that the attacks indicate the presence of an undiagnosed, life-threatening illness (e.g., cardiac disease, seizure disorder). Despite repeated medical testing and reassurance, they may remain frightened and unconvinced that they do not have a life-threatening illness. Others fear that the Panic Attacks are an indication that they are “going crazy” or losing control or are emotionally weak. Some individuals with recurrent Panic Attacks significantly change their behavior (e.g., quit a job, avoid physical exertion) in response to the attacks, but deny either fear of having another attack or concerns about the consequences of their Panic Attacks. Concerns about the next attack, or its implications, are often associated with development of avoidant behavior that may meet criteria for Agoraphobia, in which case Panic Disorder With Agoraphobia is diagnosed.

Associated Features and Disorders

Associated descriptive features and mental disorders. In addition to worry about Panic Attacks and their implications, many individuals with Panic Disorder also report constant or intermittent feelings of anxiety that are not focused on any specific situation or event. Others become excessively apprehensive about the outcome of routine activities and experiences, particularly those related to health or separation from loved ones. For example, individuals with Panic Disorder often anticipate a catastrophic outcome from a mild physical symptom or medication side effect (e.g., thinking that a headache indicates a brain tumor or a hypertensive crisis). Such individuals are also much less tolerant of medication side effects and generally need continued reassurance in order to take medication. In individuals whose Panic Disorder has not been treated or was misdiagnosed, the belief that they have an undetected life-threatening illness may lead to both chronic debilitating anxiety and excessive visits to health care facilities. This pattern can be both emotionally and financially disruptive.

In some cases, loss or disruption of important interpersonal relationships (e.g., leaving home to live on one’s own, divorce) is associated with the onset or exacerbation of Panic Disorder. Demoralization is a common consequence, with many individuals becoming discouraged, ashamed, and unhappy about the difficulties of carrying out their normal routines. They often attribute this problem to a lack of “strength” or “character.” This demoralization can become generalized to areas beyond specific panic-related problems. These individuals may frequently be absent from work or school for doctor and emergency-room visits, which can lead to unemployment or dropping out of school.

Reported rates for comorbid Major Depressive Disorder vary widely, ranging from 10% to 65% in individuals with Panic Disorder. In approximately one-third of individuals with both disorders, the depression precedes the onset of Panic Disorder. In the remaining two-thirds, depression occurs coincident with or following the onset of Panic Disorder. A subset of individuals may treat their anxiety with alcohol or medications, and some of them may develop a Substance-Related Disorder as a consequence.

Comorbidity with other Anxiety Disorders is also common, especially in clinical settings and in individuals with more severe Agoraphobia. Social Phobia and Generalized Anxiety Disorder have been reported in 15%-30% of individuals with Panic Disorder, Specific Phobia in 2%-20%, and Obsessive-Compulsive Disorder in up to 10%. Although the literature suggests that Posttraumatic Stress Disorder has been reported in 2%-10% of those with Panic Disorder, some evidence suggests that rates may be much higher when posttraumatic symptoms are systematically queried. Separation Anxiety Disorder in childhood has been associated with this disorder. Comorbidity and symptom overlap with Hypochondriasis are common.

Associated laboratory findings. No laboratory findings have been identified that are diagnostic of Panic Disorder. However, a variety of laboratory findings have been noted to be abnormal in groups of individuals with Panic Disorder relative to control subjects. Some individuals with Panic Disorder show signs of compensated respiratory alkalosis (i.e., decreased carbon dioxide and decreased bicarbonate levels with an almost normal pH). Panic Attacks in response to panic provocation procedures such as sodium lactate infusion or carbon dioxide inhalation are more common in individuals with Panic Disorder than in control subjects or individuals with Generalized Anxiety Disorder.

Associated physical examination findings and general medical conditions. Transient tachycardia and moderate elevation of systolic blood pressure may occur during some Panic Attacks. Studies have identified significant comorbidity between Panic Disorder and numerous general medical symptoms and conditions, including, but not limited to, dizziness, cardiac arrhythmias, hyperthyroidism, asthma, chronic obstructive pulmonary disease, and irritable bowel syndrome. However, the nature of the association (e.g., cause-and-effect) between Panic Disorder and these conditions remains unclear. Although studies have suggested that both mitral valve prolapse and thyroid disease are more common among individuals with Panic Disorder than in the general population, others have found no differences in prevalence.

Specific Culture and Gender Features
In some cultures, Panic Attacks may involve intense fear of witchcraft or magic. Panic Disorder as described here has been found in epidemiological studies throughout the world. Moreover, a number of conditions included in the “Glossary of Culture-Bound Syndromes” may be related to Panic Disorder. Some cultural or ethnic groups restrict the participation of women in public life, and this must be distinguished from Agoraphobia. Panic Disorder Without Agoraphobia is diagnosed twice as often and Panic Disorder With Agoraphobia three times as often in women as in men.

Prevalence
Although lifetime prevalence rates of Panic Disorder (With or Without Agoraphobia) in community samples have been reported to be as high as 3.5%, most studies have found rates between 1% and 2%. One-year prevalence rates are between 0.5% and 1.5%. The prevalence rates of Panic Disorder in clinical samples are considerably higher. For example, Panic Disorder is diagnosed in approximately 10% of individuals referred for mental health consultation. In general medical settings, prevalence rates vary from 10% to 30% in vestibular, respiratory, and neurology clinics to as high as 60% in cardiology clinics. Approximately one-third to one-half of individuals diagnosed with Panic Disorder in community samples also have Agoraphobia, although a much higher rate of Agoraphobia is encountered in clinical samples.

Course
Age at onset for Panic Disorder varies considerably, but is most typically between late adolescence and the mid-30s. There may be a bimodal distribution, with one peak in late adolescence and a second smaller peak in the mid-30s. A small number of cases begin in childhood, and onset after age 45 years is unusual but can occur. Retrospective descriptions by individuals seen in clinical settings suggest that the usual course is chronic but waxing and waning. Some individuals may have episodic outbreaks with years of remission in between, and others may have continuous severe symptomatology. Limited symptom attacks may come to be experienced with greater frequency if the course of the Panic Disorder is chronic. Although Agoraphobia may develop at any point, its onset is usually within the first year of occurrence of recurrent Panic Attacks. The course of Agoraphobia and its relationship to the course of Panic Attacks are variable. In some cases, a decrease or remission of Panic Attacks may be followed closely by a corresponding decrease in agoraphobic avoidance and anxiety. In others, Agoraphobia may become chronic regardless of the presence or absence of Panic Attacks. Some individuals report that they can reduce the frequency of Panic Attacks by avoiding certain situations. Naturalistic follow-up studies of individuals treated in tertiary care settings (which may select for a poor-prognosis group) suggest that, at 6-10 years posttreatment, about 30% of individuals are well, 40%-50% are improved but symptomatic, and the remaining 20%-30% have symptoms that are the same or slightly worse.

Familial Pattern
First-degree biological relatives of individuals with Panic Disorder are up to 8 times more likely to develop Panic Disorder. If the age at onset of the Panic Disorder is before 20, first-degree relatives have been found to be up to 20 times more likely to have Panic Disorder. However, in clinical settings, as many as one-half to three-quarters of individuals with Panic Disorder do not have an affected first-degree biological elative. Twin studies indicate a genetic contribution to the development of Panic Disorder.

Differential Diagnosis
Panic Disorder is not diagnosed if the Panic Attacks are judged to be a direct physiological consequence of a general medical condition, in which case an Anxiety Disorder Due to a General Medical Condition is diagnosed. Examples of general medical conditions that can cause Panic Attacks include hyperthyroidism, hyperparathyroidism, pheochromocytoma, vestibular dysfunctions, seizure disorders, and cardiac conditions (e.g., arrhythmias, supraventricular tachycardia). Appropriate laboratory tests (e.g., serum calcium levels for hyperparathyroidism) or physical examinations (e.g., for cardiac conditions) may be helpful in determining the etiological role of a general medical condition. Panic Disorder is not diagnosed if the Panic Attacks are judged to be a direct physiological consequence of a substance (i.e., a drug of abuse, a medication), in which case a Substance-Induced Anxiety Disorder is diagnosed . Intoxication with central nervous system stimulants (e.g., cocaine, amphetamines, caffeine) or cannabis and withdrawal from central nervous system depressants (e.g., alcohol, barbiturates) can precipitate a Panic Attack. However, if Panic Attacks continue to occur outside of the context of substance use (e.g., long after the effects of intoxication or withdrawal have ended), a diagnosis of Panic Disorder should be considered. In addition, because Panic Disorder may precede substance use in some individuals and may be associated with increased substance use for purposes of self-medication, a detailed history should be taken to determine if the individual had Panic Attacks prior to excessive substance use. If this is the case, a diagnosis of Panic Disorder should be considered in addition to a diagnosis of Substance Dependence or Abuse. Features such as onset after age 45 years or the presence of atypical symptoms during a Panic Attack (e.g., vertigo, loss of consciousness, loss of bladder or bowel control, headaches, slurred spech, or amnesia) suggest the possibility that a general medical condition or a substance may be causing the Panic Attack symptoms.

Panic Disorder must be distinguished from other mental disorders (e.g., other Anxiety Disorders and Psychotic Disorders) that have Panic Attacks as an associated feature. By definition, Panic Disorder is characterized by recurrent, unexpected (spontaneous, uncued, “out of the blue”) Panic Attacks. As discussed earlier, there are three types of Panic Attacks—unexpected, situationally bound, and situationally predisposed. The presence of recurrent unexpected Panic Attacks either initially or later in the course is required for the diagnosis of Panic Disorder. In contrast, Panic Attacks that occur in the context of other Anxiety Disorders are situationally bound or situationally predisposed (e.g., in Social Phobia cued by social situations; in Specific Phobia cued by an object or situation; in Generalized Anxiety Disorder cued by worry; in Obsessive-Compulsive Disorder cued by thoughts of or exposure to the object or situation related to an obsession [e.g., exposure to dirt in someone with an obsession about contamination]; in Posttraumatic Stress Disorder cued by stimuli recalling the stressor). In some cases, the individual may have difficulty identifying cues triggering a Panic Attack. For example, an individual with Posttraumatic Stress Disorder may have a Panic Attack triggered by cognitions or physiological symptoms similar to those that occurred at the time of the traumatic event (e.g., cardiac arrhythmias, feelings of detachment). These cues may not be easily associated by the individual with the triggering event. If the Panic Attacks occur only in situations that can be associated with the traumatic event, then the Panic Attacks should be attributed to the Posttraumatic Stress Disorder. For example, if a person who had been raped while at home alone experiences Panic Attacks only when others are not around, a diagnosis of Posttraumatic Stress Disorder should be considered instead of a diagnosis of Panic Disorder. Hoever, if the person experiences unexpected Panic Attacks in other situations, then an additional diagnosis of Panic Disorder should be considered.

The focus of the anxiety also helps to differentiate Panic Disorder With Agoraphobia from other disorders characterized by avoidant behaviors. Agoraphobic avoidance is associated with anxiety about the possibility of having a Panic Attack or panic-like sensations, whereas avoidance in other disorders is associated with concern about the negative or harmful consequences arising from the feared object or situation (e.g., scrutiny, humiliation, and embarrassment in Social Phobia; falling from a high place in Specific Phobia of heights; separation from parents in Separation Anxiety Disorder; persecution in Delusional Disorder).

Differentiation of Specific Phobia, Situational Type, from Panic Disorder With Agoraphobia may be particularly difficult because both disorders may include Panic Attacks and avoidance of similar types of situations (e.g., driving, flying, public transportation, enclosed places). Prototypically, Panic Disorder With Agoraphobia is characterized by the initial onset of unexpected Panic Attacks and the subsequent avoidance of multiple situations thought to be likely triggers of the Panic Attacks. Prototypically, Specific Phobia, Situational Type, is characterized by situational avoidance in the absence of recurrent unexpected Panic Attacks. Some presentations fall between these prototypes and require clinical judgment in the selection of the most appropriate diagnosis. Four factors can be helpful in making this judgment: the focus of anxiety, the type and number of Panic Attacks, the number of situations avoided, and the level of intercurrent anxiety. For example, an individual who had not previously feared or avoided elevators has a Panic Attack in an elevator and begins to dread going to work because of the need to take the elevator to his office on the 24th floor. If this individual subsequently has Panic Attacks only in elevators (even if the focus of anxiety is on the Panic Attack), then a diagnosis of Specific Phobia may be appropriate. If, however, the individual experiences unexpected Panic Attacks in other situations and begins to avoid or endure with dread other situations because of anxious anticipation of a Panic Attack, then a diagnosis of Panic Disorder With Agoraphobia would be warranted. Furthermore, the presence of pervasive apprehension about having a Panic Attack even when not anticipating exposure to a phobic situation also supports a diagnosis of Panic Disorder With Agoraphobia. If the individual has additional unexpected Panic Attacks in other situations but no additional avoidance or endurance with dread develops, then the appropriate diagnosis would be Panic Disorder Without Agoraphobia. If th focus of avoidance is not related to having a Panic Attack but concerns some other catastrophe (e.g., injury due to the elevator cable breaking), then an additional diagnosis of Specific Phobia may be considered.

Similarly, distinguishing between Social Phobia and Panic Disorder With Agoraphobia can be difficult, especially when there is avoidance only of social situations. For example, individuals with Panic Disorder With Agoraphobia and those with Social Phobia may both avoid crowded situations (e.g., large shopping centers, crowded parties). The focus of anxiety and the type of Panic Attacks can be helpful in making this distinction. For example, an individual who had not previously had a fear of public speaking has a Panic Attack while giving a talk and begins to dread giving presentations. If this individual subsequently has Panic Attacks only in social performance situations and if these attacks are accompanied by a fear of being embarrassed and humiliated, then a diagnosis of Social Phobia may be appropriate. If, however, the individual continues to experience unexpected Panic Attacks in other situations, then a diagnosis of Panic Disorder With Agoraphobia would be warranted. Individuals with Social Phobia fear scrutiny and rarely have a Panic Attack when alone (unless when anticipating a social situation), whereas individuals with Panic Disorder With Agoraphobia may be more anxious in situations where they must be without a trusted companion. In addition, nocturnal Panic Attacks that awaken an individual from sleep are characteristic of Panic Disorder.

When criteria are met for both Panic Disorder and another Anxiety or Mood Disorder, both disorders should be diagnosed. However, if unexpected Panic Attacks occur in the context of another disorder (e.g., Major Depressive Disorder or Generalized Anxiety Disorder) but are not accompanied by a month or more of fear of having additional attacks, associated concerns, or behavior change, the additional diagnosis of Panic Disorder is not made. Because individuals with Panic Disorder may self-medicate their symptoms, comorbid Substance-Related Disorders (most notably related to cannabis, alcohol, and cocaine) are not uncommon.

Diagnostic criteria for Panic Disorder Without Agoraphobia

A. Both (1) and (2):

• (1) recurrent unexpected Panic Attacks
• (2) at least one of the attacks has been followed by 1 month (or more) of one (or more) of the following:
• (a) persistent concern about having additional attacks
• (b) worry about the implications of the attack or its consequences (e.g., losing control, having a heart attack, “going crazy”)
• (c) a significant change in behavior related to the attacks

B. Absence of Agoraphobia.

C. The Panic Attacks are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism). D. The Panic Attacks are not better accounted for by another mental disorder, such as Social Phobia (e.g., occurring on exposure to feared social situations), Specific Phobia (e.g., on exposure to a specific phobic situation), Obsessive-Compulsive Disorder (e.g., on exposure to dirt in someone with an obsession about contamination), Posttraumatic Stress Disorder (e.g., in response to stimuli associated with a severe stressor), or Separation Anxiety Disorder (e.g., in response to being away from home or close relatives).

Diagnostic criteria for Panic Disorder With Agoraphobia

A. Both (1) and (2):

• (1) recurrent unexpected Panic Attacks
• (2) at least one of the attacks has been followed by 1 month (or more) of one (or more) of the following:
• (a) persistent concern about having additional attacks
• (b) worry about the implications of the attack or its consequences (e.g., losing control, having a heart attack, “going crazy”)
• (c) a significant change in behavior related to the attacks

B. The presence of Agoraphobia.
C. The Panic Attacks are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism).
D. The Panic Attacks are not better accounted for by another mental disorder, such as Social Phobia (e.g., occurring on exposure to feared social situations), Specific Phobia (e.g., on exposure to a specific phobic situation), Obsessive-Compulsive Disorder (e.g., on exposure to dirt in someone with an obsession about contamination), Posttraumatic Stress Disorder (e.g., in response to stimuli associated with a severe stressor), or Separation Anxiety Disorder (e.g., in response to being away from home or close relatives).