Phenomenology and epidemiology of panic disorder
Research Psychiatrist, Laureate Institute of Brain Research, Professor of Research, University of Oklahoma College of Medicine, Tulsa, OK, USA
BACKGROUND: Panic disorder is a common and severe psychiatric disorder. The estimated current prevalence rate for panic disorder is 1% to 2% of the adult population. Panic disorder is commonly accompanied by major depression, substance use disorders, and other anxiety disorders. Female gender, low socioeconomic status, and anxious childhood temperament are common risk factors for panic disorder. Panic disorder can produce marked distress and impairment and is associated with significant suicide risk. Panic disorder appears to increase risk for all-cause mortality because it may increase risk for cardiovascular disease.
KEYWORDS: panic disorder, panic attacks, epidemiology
ANNALS OF CLINICAL PSYCHIATRY 2009;21(2):95–102
Panic disorder with or without agoraphobia is a common mental disorder with significant clinical manifestations.1 The disorder typically features a variety of physical symptoms that prompt patients to seek medical as well as mental health care. Panic is associated with increased suicide and medical mortality and morbidity, underscoring its importance. Effective treatments are available, making early diagnosis essential.
Sigmund Freud in 1894 presented a classic description of the symptoms of panic in discriminating anxiety neurosis and neurasthenia.2 The understanding of panic disorder’s phenomenology grew following the description of the disorder in the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, published in 1980.3 This definition evolved from criteria that had been proposed by Feighner.4 Prior to this time, panic disorder’s clinical features had been recognized but were incorporated in the more general category of anxiety neurosis. With this evolution to a more distinct diagnostic category, panic disorder became a subject of study within the medical model.5 Panic disorder research covering diagnostic specificity, prevalence, risk factors, outcome, and treatment response significantly expanded.6-13
Panic attacks are the hallmark of panic disorder. These attacks typically emerge rapidly and include a cluster of symptoms involving the emotional, cognitive, and somatic domains. TABLE 1 presents the 13 symptoms of panic attack according to symptom domain. The attacks are extremely frightening and distressful to patients. Initial attacks are often interpreted as evidence of a catastrophic physical disorder, such as a myocardial infarction or respiratory failure. Following initial panic, patients frequently develop anticipatory anxiety—a fear that future attacks will occur. Anticipatory anxiety can include preoccupation with thoughts of how to avoid or reduce the likelihood of such attacks. Physical symptoms and worry concerning attacks commonly induce hypochondriacal concerns.14
Panic episodes that fail to meet criteria for a panic attack are termed limited-symptom attacks. Patients with panic disorder often have limited-symptom attacks as well as attacks that meet the full criteria. Response to treatment may be initially seen as conversion of full-blown attacks to limited-symptom attacks.15
Agoraphobia is a behavioral response to panic attacks that attempts to reduce the frequency of attacks. Patients may come to associate panic attacks with specific situations or settings. TABLE 2 outlines the key situations related to agoraphobia. These situations or settings are then avoided. Common situations in which panic attacks occur are those where the patient feels crowded, confined, and without an easy exit. Such situations include large crowds, being in an airplane or bus, attending the movies or religious services, or being in novel situations away from sources of support such as a spouse. Although the goal of this avoidance behavior is to reduce the frequency of attacks, it may result in a restricted lifestyle and impairment in occupational and interpersonal functioning. There continues to be some controversy as to whether agoraphobia is simply a consequence of panic disorder or a separate disorder. Family studies suggest that agoraphobia is a more severe variant of panic disorder.16 However, agoraphobia also occurs independent of panic disorder and may be associated with other anxiety disorders, such as social and blood-injection phobia.17
Early classifiers recognized that panic attacks are not unique to panic disorder. Such attacks can be precipitated by a variety of phobic stimuli. They commonly occur in social situations in those who have social anxiety disorder. They may also be stimulated by traumatic cues in those with posttraumatic stress disorder. Panic attacks may occur with specific phobias, such as needle or spider phobia. However, a diagnosis of panic disorder requires that at least some attacks occur de novo, without a specific stimulus. Patients with panic disorder often are troubled by spontaneous attacks as well as attacks provoked by environmental stimuli.
Key characteristics of panic attack*
||• Palpitations, pounding heart, tachycardia
• Chest pain or discomfort
• Chills or hot flushes
• Trembling or shaking
||• Shortness of breath or smothering sensation
||• Dizziness or lightheadedness
• Nausea or abdominal distress
• Fear of losing control or “going crazy”
Key situations related to agoraphobia
|Anxiety in situations where escape is difficult or help is not available
|• Being outside home alone
|• Being in a crowd
|• Being in a line
|• Being on a bridge
|• Traveling in crowded conditions, eg, bus, plane, car
Three major studies of the epidemiology of panic disorder in the United States have been performed since the development of the DSM-III criteria. The first was the Epidemiologic Catchment Area (ECA) study, which was conducted from 1980 to 1984 at 5 regional centers.18 The second was the National Comorbidity Survey (NCS), conducted from 1990 to 1992, using a national sample.19 A replication of the National Comorbidity Survey (NCSR) is the most recent, taking place from 2001 to 2003.20 All 3 studies included direct interviews to determine the presence of panic and other common mental disorders.
Recent studies have included estimates of the specific prevalence and correlates of panic attacks. In the ECA study, 383 (3.0%) participants developed panic attacks, in a cohort of >12,000 patients who were followed for 1 year,11 with a lifetime prevalence rate of 7.3%. An ancillary study of panic attack frequency was completed using the large Women’s Health Initiative (WHI) cohort.21 The 6-month prevalence rate for panic attacks was 9.8%, and the rate for limited-symptom attacks was 8.1%.
The NCS included >8000 community participants age 15 to 54. Of the sample, 15% reported a lifetime history of ≥1 panic attack, with 1% meeting criteria for DSM-III panic disorder within the last month and 2% meeting criteria for a lifetime diagnosis.9
The NCS-R study provides some additional information about the prevalence and phenomenology of panic disorder.10 A lifetime history of any panic attacks was endorsed by 28.3% of the sample. Lifetime prevalence of panic disorder was estimated at 4.8%. Of those with panic disorder, 23% also had agoraphobia. A small group (0.8%) with lifetime panic attacks but not panic disorder met the criteria for agoraphobia. The survey includes measures of severity. Of those with panic disorder and agoraphobia, 86% were rated as moderate or severe on clinical severity. Of those with panic disorder alone, 46% were rated as moderate or severe on clinical severity.
The NCS-R study raised the issue of a fairly large number of people with panic attacks but without a diagnosis of panic disorder. Many of these individuals had relatively frequent and severe attacks but did not meet the criteria for panic disorder because of the absence of uncued (unexpected) attacks. Further study of panic attacks without panic disorder—especially when accompanied by agoraphobia—is needed to determine the clinical importance of these attacks.
International studies of panic disorder suggest a lifetime prevalence rate of 2%, with a 12-month prevalence rate around 1%.22 Panic attacks occur across all cultures and nations studied. Panic disorder appears to be a common—and often unrecognized—condition in primary care.
The onset of panic disorder typically occurs during the late teens or early 20s. This is somewhat later than other anxiety disorders such as social phobia.
Early studies of panic disorder demonstrated that female gender was a significant risk factor for panic disorder. The female-to-male ratio for panic disorder has been estimated at 2 to 2.5. The reason for this gender association is unknown. Other anxiety disorders, such as generalized anxiety disorder and social phobia, typically have odds ratios of about 1.3 to 2.0 for female gender. Other risk factors with validated association in panic disorder include low educational attainment and low income status. Panic disorder is also associated with a history of divorce. In the ECA study, history of divorce was endorsed by about 25% of subjects with panic disorder, compared to approximately 10% of those with no active DSM-III diagnosis.
Panic attacks and panic disorder appear to be more likely in those in the 18-to-45 year age group. Lower rates of panic disorder are typically seen in persons age 65 and older. The reason for this lower rate is unknown but may reflect a tendency for panic attacks to abate over time and may also be an effect of increased mortality in panic disorder. Many patients with panic disorder have a favorable prognosis but continue to have some residual symptoms.
Traumatic brain injury increases the risk for a variety of psychiatric disorders, including many of the anxiety disorders.23 A study of the ECA sample found that panic disorder occurred in 3.2% of community subjects who had had a head injury, compared with only 1.3% of those with no history of such injury. This finding produces an odds ratio estimate of 2.8 for panic disorder in those with brain injury. After controlling for alcohol abuse, the odds ratio for panic disorder in brain injury patients was reduced slightly to 2.5, but remained the highest among Axis I disorders.
Several childhood markers for adult panic disorder appear to exist. Children with behavioral inhibition appear to have an increased risk for the later development of panic disorder.24 Behavioral inhibition is a style of reacting when children are confronted with novel situations or unknown adults. It includes symptoms of anxiety and withdrawal in these situations. Childhood temperamental emotional reactivity (high emotional response to stress/separation) also appears to increase panic disorder risk. A developmental history of pulmonary disease is also linked to later panic disorder.25
Adolescents who develop early-onset heavy smoking behavior have an increased risk for panic disorder.26 A summary of the known risk factors for panic disorder is shown in TABLE 3.
Risk factors for panic disorder
|• Female gender
|• Low socioeconomic status
|• Single/divorced marital status
|• Age 18 to 45
|• Traumatic brain injury
|• Childhood behavioral inhibition/emotional reactivity
|• Childhood respiratory ill health
|• Early-onset heavy cigarette smoking
For many patients, panic disorder produces a significant impairment in function. Panic attacks can also reduce the effectiveness of interpersonal relationships. Panic disorder patients may avoid social situations in which they fear an increased risk for panic attacks. High-risk work-related triggers may also be avoided and result in increased work absence or inability to work.
Panic disorder is a heterogeneous condition with a range of severity and variable outcomes. Environmental factors appear to influence the outcome. Noyes demonstrated that a history of having been separated from parents by death or divorce resulted in a poorer outcome for panic disorder.27 Additionally, low socioeconomic status and being unmarried conferred increased risk for poor outcome.
Personality disorder also appears to be associated with a poor outcome in panic disorder.28 Personality disorder, major depression, and severe phobic avoidance predicted poor outcome in a follow-up study of 89 patients with panic disorder.28 Personality disorder appeared to be the strongest predictor among comorbid mental disorders.
Comorbid panic disorder in medical patients can adversely influence medical outcome. Symptoms of panic disorder may overlap with symptoms of medical conditions, resulting in unsatisfactory response to standard medical therapies. Panic disorder is commonly seen in patients treated for chest pain. In a study of initial referrals to a cardiology clinic, 16% were diagnosed with coronary artery disease and 38% had panic disorder.29 In 9 years of follow-up of this cohort, no increased mortality was associated with a diagnosis of panic disorder. However, panic disorder patients continued to have higher scores on chest pain intensity and higher impairment in quality of life and physical functioning. Up to 40% of patients with chest pain and normal coronary arteries have panic disorder.29 These studies highlight the importance of assessment and management of panic disorder in high-risk medical conditions.
It is important to note that successful treatment of panic disorder reduces the intensity of physical and hypochondriacal symptoms.30,31 When panic attacks are successfully reduced, so too are hypochondriacal preoccupations and panic-related physical symptoms. Successful treatment of panic disorder not only reduces emotional pain but also physical pain that patients experience.
The natural history of panic disorder is consistent with that of a chronic disease, but with a favorable outcome in most patients over time.13 In one early study, treatment with tricyclic antidepressants posed significant treatment challenges with poor drug tolerability.32 More recent antidepressants, including selective serotonin reuptake inhibitors (SSRIs), are better tolerated, and along with new psychotherapeutic options improve the outcome for many panic disorder patients.33,34
Psychiatric disorders. Major depression is the psychiatric disorder with the strongest link to panic disorder. The lifetime prevalence of major depression in panic disorder is estimated at 50% to 60%.1 In about two-thirds of cases panic disorder precedes the onset of major depression, whereas in one-third major depression precedes the onset of panic disorder.
Agoraphobia is strongly linked to panic disorder. Approximately one-third to one-half of patients with panic disorder also will meet the criteria for agoraphobia.
Panic disorder significantly increases the risk for additional anxiety disorders. This risk includes social phobia, posttraumatic stress disorder, obsessive-compulsive disorder, and the specific phobias. This comorbidity highlights the need to comprehensively assess the anxiety disorder domain in patients with panic disorder.
Panic disorder is associated with high rates of Axis II personality disorders. Rates of personality comorbidity have been estimated at 40% to 50% of patients. Cluster C personality disorders are common. Specific disorders that occur more frequently in patients with panic disorder include avoidant, obsessive-compulsive, and dependent personality disorders. There is evidence that successful treatment of panic disorder results in some reduction in cluster C personality traits.35
Substance use disorders also are common in patients with panic disorder.36 Stimulants may be involved in the emergence of initial panic disorder.37 Cocaine-induced panic attacks have been described. Caffeine use may increase the frequency of panic attacks and adversely affect treatment outcome. Alcohol abuse and dependence are common among patients with panic disorder.38 Alcohol use may temporarily reduce panic symptoms; however, alcohol withdrawal may precipitate and worsen panic attacks.
Medical disorders. In the ECA study, subjects with anxiety disorders endorsed a high rate of current medical conditions.39 Increased rates were found for a variety of conditions, including chronic lung disease, diabetes, heart disease, hypertension, arthritis, and physical handicap. Anxiety disorder subjects did not endorse higher rates of other conditions, such as cancer. The cause of this increased medical comorbidity is unclear but may be due in part to the effects of increased nicotine, alcohol, and drug use among persons with anxiety disorder.
There is evidence that panic attacks and panic disorder occur at rates higher than chance in a variety of medical conditions. Panic attacks appear frequently in patients who report having asthma.40,41 Rates of panic attack have been estimated at 2 to 6 times that for persons without asthma. Panic attack occurrence is related to the severity and persistence of asthma over time. The authors of one study note that this association could be causal (ie, asthma causing panic attacks) or due to a common genetic or environmental factor.
Panic attacks in postmenopausal women from the WHI study were more common in women with migraine, emphysema, cardiovascular disease, and chest pain during ambulatory ECG monitoring.21 Of note, panic attacks did not occur more frequently in women reporting hormone replacement therapy.
Symptoms of autonomic hyperactivity in panic disorder support the potential for cardiovascular dysfunction in this population. Patients with hypertension have approximately a 2-fold increase in rates of panic attacks and panic disorder.42 Panic attacks dominated by autonomic symptoms are more commonly associated with hypertension.43
Rates of migraine headache are increased in panic disorder as well as in major depression and bipolar disorder.44 Epilepsy appears to significantly increase the risk for panic disorder.45 Of note, panic attacks in patients with epilepsy appear to be dominated by psychological symptoms rather than cardiovascular symptoms.
Panic attacks and panic disorder appear to be increased in a variety of conditions characterized by physical pain. A twin study demonstrated increased rates of panic attack and panic disorder in twins with chronic fatigue syndrome, low back pain, irritable bowel syndrome, fibromyalgia, and temporomandibular joint syndrome.46
Lee et al47 examined the prevalence of restless legs syndrome among those with panic disorder and major depression. Panic disorder produced an increased odds ratio of 12.9 for restless legs syndrome compared with those without panic disorder. A summary of the medical disorders associated with an increased risk of panic attack and panic disorder is shown in TABLE 4.
Early studies found an increased rate of cardiovascular death in men with anxiety neurosis.48,49 A recent large naturalistic study examined the role of panic attacks in women.50 More than 3000 postmenopausal women were followed for 5 years. Ten percent of the women reported panic attacks at baseline. These women had increased rates of cardiovascular disease, stroke, and overall mortality in the follow-up period. The odds ratio for cardiovascular disease was elevated 4-fold, and overall mortality was increased approximately 2-fold.
Medical conditions with increased rates of panic attack or panic disorder
|• Migraine headache
|• Restless legs syndrome
|• Chronic fatigue syndrome
|• Low back pain
|• Irritable bowel syndrome
|• Temporomandibular joint syndrome
Panic disorder increases utilization of both medical and mental health services. Medical care utilization by persons with panic disorder tends to be higher than for those with other anxiety disorders or major depression.51,52 Patients with panic disorder frequently attribute the symptoms of panic attacks to medical causes. Early medical care interaction frequently involves seeking out a medical explanation for the symptoms in the emergency room as well as primary care and specialty practices.
In the NCS-R, approximately 20% of patients with a diagnosis of panic disorder were seeking treatment in the mental health domain. This is a rate of contact higher than that of most anxiety disorders. Only posttraumatic stress disorder approached this rate of mental health contact. Rates of seeking mental health treatment for panic disorder are similar to those for major depression and bipolar disorder.
Panic disorder increases the frequency of contact with medical services. Many patients are seen only in the medical care setting and have no contact with mental health care providers. The NCS survey documented that 40% of community subjects with panic disorder had seen medical providers in the last year. This is the highest rate of contact among all mental disorders and underscores the prevalence of panic disorder among patients seen by general medical providers. Unless general practice physicians have specialized training in panic disorder, patients with contact only in the medical care domain are less likely to receive adequate care for their panic disorder.
The NCS-R study confirmed the high utilization rate for panic disorder.53 The 12-month mental health specialty contact rate was 34.7% for panic disorder. General medical care was sought by 43.7% of those surveyed. Combined, 59.1% of panic disorder subjects were treatment seeking. This is the highest treatment-seeking rate for all psychiatric disorders except for those with dysthymia (61.1%). The increase in treatment rates between the NCS and NCS-R surveys supports the need for improved recognition and treatment of panic disorder.
There is some evidence that successful treatment of panic disorder reduces overall medical and mental health care utilization.54 This increases the importance of accurate diagnosis by both primary care and mental health practitioners.
Panic disorder and suicide
The role of panic disorder in suicidal behavior and completed suicide is complex55 and has been a subject of significant interest. Major depression, substance use disorders, and personality disorders all increase the risk for suicide, and all of these disorders frequently coexist with panic disorder.
An early study using the ECA study sample found that panic disorder was associated with an 18-fold increase in risk for suicide attempt.56 This risk was reduced to an odds ratio of 2.6 when adjusted for the presence of other psychiatric disorders. However, a later study using the same data set failed to find a specific effect of panic disorder on suicide attempt frequency.57
This later study used a more comprehensive approach to controlling for the effects of comorbid diagnosis. A study of the NCS sample confirmed the lack of specific risk for suicide attempt in panic disorder.58 Most experts agree that the suicide risk in panic disorder occurs primarily among those with psychiatric comorbidities.
In an early study of panic disorder outcome and suicide, Noyes et al59 examined the 7-year outcome of a group of 74 subjects with panic disorder. Completed suicide occurred in 4% of the sample, with >6% of subjects exhibiting serious suicide attempts. Suicidal behavior in this population was associated with early age of onset of panic disorder, increased panic disorder severity, and comorbid major depression and personality disorder. Clinicians should carefully assess suicidal ideation and suicidal planning in patients with panic disorder. Understanding the effects of panic disorder severity and comorbidity on suicide risk provides additional perspective in assessing risk.
Since 1980, significant incremental advances have been made in our understanding of the phenomenology and epidemiology of panic attacks and panic disorder. Identification of the disorder, diagnosis, and appropriate treatment continue to be important in primary care and specialty practice. The medical model approach has successfully improved assessment and understanding of medical and psychiatric comorbidity issues in panic disorder. This progress provides a framework for active research in molecular biology, genetics, and brain imaging in panic disorder.
DISCLOSURE: The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
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CORRESPONDENCE: William R. Yates, MD, 8601 S Darlington Ave, Tulsa, OK 74137 USA. E-MAIL: firstname.lastname@example.org
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