Agoraphobia in adults - Epidemiology, pathogenesis, clinical manifestations, course, and...

Official reprint from UpToDatewww.uptodate.com ©2013 UpToDate

AuthorRandi E. McCabe, PhD

Section EditorMurray B Stein, MD, MPH

Deputy EditorRichard Hermann, MD

Agoraphobia in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Oct 2013. | This topic last updated: Set 9, 2013.

INTRODUCTION — Agoraphobia is defined in DSM-5 as fear or anxiety about and/or avoidance of situationswhere help may not be available or where it may be difficult to leave the situation in the event of developingpanic-like symptoms or other incapacitating or embarrassing symptoms [1]. Patterns of agoraphobic avoidancemay range from just a few situations (eg, driving and crowds) to multiple situations. In severe cases, the individualbecomes housebound, rarely leaving the house and, if so, only when accompanied.

Although the likelihood of agoraphobia is increased when panic symptoms are present, agoraphobia can occuralone or concurrently with panic disorder [2-4]. With the revision of DSM-IV to DSM-5, agoraphobia is diagnosedindependently of panic disorder [1]. The presence of agoraphobia is associated with significant impairment infunctioning, degree of disability, and unemployment [4]. The disorder is treatable with various forms of cognitivebehavioral treatment and antidepressant medication. More severe cases of agoraphobia may pose treatmentchallenges [5].

The epidemiology, pathogenesis, clinical manifestations, course, and diagnosis of agoraphobia in adults arereviewed here. Treatment of agoraphobia is reviewed separately. Specific phobia and panic disorder in adults, andphobias in children, are reviewed separately. (See "Specific phobia in adults: Epidemiology, clinical manifestations,course and diagnosis" and "Panic disorder: Epidemiology, pathogenesis, clinical manifestations, course,assessment, and diagnosis" and "Overview of fears and specific phobias in children" and "Pharmacotherapy forpanic disorder" and "Psychotherapy for panic disorder".)

EPIDEMIOLOGY — Agoraphobia most commonly occurs in conjunction with panic disorder with lifetime prevalencerate of 1.1 percent [6]. Lifetime prevalence rate of agoraphobia without panic disorder is lower, estimated at 0.8percent in a large community survey [6]. However, a prospective longitudinal study targeting an adolescent/youngadult sample (representing what is considered to be the high-risk age range for psychopathology development)found a much higher incidence when DSM-IV rules requiring agoraphobia to be diagnosed within the context ofpanic disorder were not used, compared to when they were (5.3 percent versus 0.6 percent) [2]. (See "Panicdisorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

Earlier studies reported lower rates of agoraphobia in older adults compared to younger adults [7,8]. In contrast, apopulation-based study of adults 65 years and older in France found agoraphobia to be common, with one-monthand lifetime prevalence estimates of 10 and 17 percent [9]. Among participants without a prior history, 11 percentreported new onset of agoraphobia over the following four years; its occurrence was frequently associated withsevere depression.

A review of epidemiological studies found that 46 to 85 percent of individuals with agoraphobia did not report panicattacks [10]. However, prevalence of agoraphobia without panic attacks in clinical samples is low [10], which maybe due to the impediments that a patient with the condition (ie, avoidance) faces in seeking treatment. Agoraphobiais more common in women than men [6].

Risk factors for agoraphobia include the presence of panic disorder, younger age, female gender and otherphobias [11]. Degree of agoraphobic avoidance is a more influential predictor of disability than frequency andseverity of panic attacks [12]. In the context of panic disorder, the presence of agoraphobia is associated withincreased role impairment, greater panic disorder symptom severity, and increased comorbidity with other Axis 1

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disorders compared to panic disorder without agoraphobia [6]. (See "Panic disorder: Epidemiology, pathogenesis,clinical manifestations, course, assessment, and diagnosis".)

Comorbidity patterns for agoraphobia are highest with panic disorder but also high with respect to other anxietydisorders (49 to 64 percent) and depressive disorders (33.1 to 52 percent) [4].

PATHOGENESIS — Agoraphobia was until recently widely considered to be a complication of panic disorderwherein an individual avoids situations for fear of developing a panic attack (“fear of fear”) [13,14]. Thisconceptualization is not without controversy [12,15] and the unlinking of panic disorder and agoraphobia in DSM-5reflects the current view that agoraphobia is a distinct disorder that exists independently of the presence orabsence of panic disorder. Agoraphobia has also been conceptualized more broadly as a fear of difficulty inescaping [11].

Etiology of agoraphobia involves a complex interaction of biological, psychological, and environmental factors:

Genetic factors — Clinical and non-clinical family studies show evidence of familial aggregation in the etiology ofagoraphobia [16,17]. The presence of parental agoraphobia and panic disorder increases the risk for any anxietydisorder rather than for agoraphobia or panic disorder specifically [18]. The heritability estimates of agoraphobiarange from 48 to 61 percent [19-21]. Overall, evidence suggests moderate genetic influences with nonsharedenvironmental factors being more influential, and no evidence for shared environmental contribution [20].Genetically-based dispositional factors may also play a role. (See 'Personality factors' below.)

Personality factors — In addition to broad based constructs such as neuroticism that have been shown to play adevelopmental role broadly across anxiety and mood disorders [22], dispositional factors have been shown to havea specific association with agoraphobia.

Extroversion/introversion — Extroversion has been negatively associated with agoraphobia but not panicdisorder. Low extroversion (ie, high introversion) has been associated with increased odds of a lifetimeagoraphobia diagnosis [23-25]. Further research shows that extroversion is associated with the presenceand severity of situational avoidance [26]. A twin study examined the independent genetic contributions ofextroversion and neuroticism on heritable influences (genetics versus shared environmental factors) ofagoraphobia [27]. Results found negative within-person correlations between extroversion and agoraphobia,and higher cross-twin correlations in monozygotic twins than dizygotic twins suggesting that the geneticcomponents that influence extroversion also affect the likelihood of a lifetime diagnosis of agoraphobia.

Anxiety sensitivity — The belief that physical symptoms of anxiety are dangerous (ie, anxiety sensitivity) hasbeen shown to predict panic disorder as well as agoraphobia without panic attacks [26,28,29].

Dependency — Avoidant, dependent and related personality traits have been found to predict the onset ofagoraphobia [30].

Other — Lack of perceived control [31] and low self-efficacy [32] have also been associated withagoraphobic avoidance and situational fear.

Cognitive factors — Expectations regarding the likelihood and harmfulness of a panic attack as well as beliefs incoping have been shown to play a role in influencing and maintaining avoidant behavior [33]. Information processingbiases in attention and memory for physical threat cues may serve to maintain the disorder, but also may have anetiological influence [34].

Social/environmental factors — Learning processes may play a significant role in the development ofagoraphobia whereby avoidance is negatively reinforced by the reduction of aversive emotional states orsymptoms of autonomic arousal [35]. As an example, an individual who experiences anxiety in a grocery storeabruptly leaves the situation and finds that leaving results in greatly reduced anxiety. The individual learns thatescape is associated with anxiety reduction and thus becomes more likely to escape in future instances of anxiety.The individual learns that this situation is associated with anxiety and may avoid the situation altogether as a meansof avoiding the experience of anxiety.

CLINICAL MANIFESTATIONS — The principal manifestation of agoraphobia is anxiety about and/or avoidance ofcertain situations. Individuals with agoraphobia will often but not always report fear of panic symptoms, and may or


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may not have a history of panic attacks. Situations avoided are summarized in a table (table 1). (See "Panicdisorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

Reasons for avoiding situations may vary. In the majority of cases, individuals describe avoiding situations for fearof experiencing panic symptoms and consequent embarrassment or feelings of helplessness. Individuals may fearbeing overwhelmed by symptoms of anxiety to the point that they lose control or die. Loss of control concerns arespecific to the individual and may include fears of loss of bowel or bladder control, vomiting, fainting, “going crazy”or becoming unable to function. In some instances, individuals may have more difficulty describing the nature oftheir fear and may report a feeling of general dread or impending doom.

In a study of 41 individuals with a lifetime history of agoraphobia grouped as those with panic disorder and thosewithout panic attacks, the most common reason for avoidance given in both groups was a fear of becoming“suddenly incapacitated” [15].

It is common for individuals with moderate to severe agoraphobia to describe having a “safe zone” within whichthey feel comfortable. This may be their house or a certain perimeter around their neighborhood. Leaving this zoneof safety may be completely avoided, particularly if travelling alone, or otherwise endured with distress. Individualswith agoraphobia often engage in safety behaviors to reduce their level of anxiety in a particular situation (table 2).Safety behaviors are actions an individual takes to prevent a feared outcome from occurring or cope with aperceived threat [36,37]. In agoraphobia, safety behaviors may be overt (eg, escape, avoidance, beingaccompanied by a “safe” person) or more subtle (eg, sitting in a location near an exit or carrying an item that isperceived to provide comfort or protection). Safety behaviors may play a role in perpetuating the disorder.

The presence of agoraphobia is associated with significant impairment in functioning, degree of disability, and levelof unemployment [4]. Help-seeking in individuals with agoraphobia without panic disorder is much lower than inindividuals with panic disorder with or without agoraphobia [38].

COURSE — Onset of agoraphobia may be sudden after experiencing an unexpected panic attack or it maygradually develop over time. The median age of onset is 20 [39], and onset before age 55 is most common [7]. Arecent study suggests that onset in later adulthood is not as uncommon as previously believed [9].

The course of agoraphobia is often chronic and unremitting without treatment. Over a follow-up period of 10 years,agoraphobia without panic attacks was found to be among the most persistent disorders, with complete remissionrarely observed [5,40]. In many studies assessing long-term outcome in panic disorder, the most consistentpredictor of poor outcome is the presence of severe agoraphobia, which has been associated with reduced rate ofremission, increased risk of relapse, and increased chronicity [4].

DIAGNOSIS — A comprehensive psychiatric assessment of a patient with possible agoraphobia should include:

The focus of the patient’s fearThe range of feared situationsReasons for avoidanceFactors that influence the nature and intensity of the fearSafety behaviors used by the patient

DSM-5 criteria for agoraphobia are described below:

A. Marked fear or anxiety about two or more of the following situations:

1. Using public transportation (eg, automobiles, buses, trains)

2. Being in open spaces (eg, parking lots, marketplaces, bridges)

3. Being in enclosed places (eg, shops, theaters, cinemas)

4. Standing in line or being in a crowd

5. Being outside of the home alone

B. The individual fears or avoids these situations because of thoughts that escape might be difficult or helpmight not be available in the event of developing panic-like symptoms or other incapacitating or


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embarrassing symptoms (eg, fear of falling in the elderly or fear of incontinence).

C. The agoraphobic situations almost always provoke fear or anxiety.

D. The agoraphobic situations are actively avoided, require the presence of a companion, or are enduredwith intense fear or anxiety.

E. The fear or anxiety is out of proportion to the actual danger posed by the agoraphobic situations and tothe sociocultural context.

F. The fear, anxiety, or avoidance is persistent, typically lasting for six months or more.

G. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational,or other important areas of functioning.

H. If another medical condition (eg, inflammatory bowel disease, Parkinson's disease) is present, the fear,anxiety, or avoidance is clearly excessive.

I. The fear, anxiety, or avoidance is not better explained by the symptoms of another mental disorder andare not related exclusively to:

A specific situation, as in specific phobia, situational type

Social situations, as in social anxiety disorder

Obsessions, as in obsessive-compulsive disorder

Perceived defects or flaws in physical appearance, as in body dysmorphic disorder

Reminders of traumatic events, as in posttraumatic stress disorder

Fear of separation, as in separation anxiety disorder

Note: Agoraphobia is diagnosed irrespective of the presence of panic disorder. If an individual's presentation meetscriteria for panic disorder and agoraphobia, both diagnoses should be assigned.

The presence of panic disorder and a history of panic attacks should be assessed given that agoraphobia oftenpresents concurrently with panic disorder or panic-like symptoms. (See "Panic disorder: Epidemiology,pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

Differential diagnosis — The fears and situational avoidance characteristic of agoraphobia overlap with a numberof disorders. Careful assessment is needed to complete a differential diagnosis.

Social anxiety disorder — In social anxiety disorder (or social phobia), fears are focused on negative evaluationby others and avoidance is typically limited to social situations. Although fear of social embarrassment from anxietysymptoms may be present in agoraphobia, it is not typically the sole focus of fear. In addition, an individual withagoraphobia will avoid situations whether people are present or not, whereas an individual with social anxietydisorder typically would feel more comfortable entering a situation if no other people were present. (See "Socialanxiety disorder: Epidemiology, clinical manifestations, and diagnosis".)

Specific phobia — In the case of multiple specific phobias and agoraphobia, a person may report avoiding arange of situations. Determining the focus of the fear in each situation will assist in distinguishing the two. Inmultiple specific phobias, fears are typically focused on specific aspects of the situation or object that differ acrossavoided situations. For example, an individual with multiple specific phobias may avoid elevators for fear ofbecoming trapped (specific phobia), driving for fear of getting in an accident (situational phobia), and walking ingrassy open areas for fear of encountering a snake (specific animal phobia). In agoraphobia, an individual may fearthese same situations (elevators, driving, walking in open areas) but the focus of fear is the same across thesituations (eg, fear of having panic symptoms, being unable to get help if needed or becoming incapacitated in thesituation.). (See "Specific phobia in adults: Epidemiology, clinical manifestations, course and diagnosis".)

Posttraumatic stress disorder — Examining triggers and the context of avoidance may distinguish posttraumaticstress disorder from agoraphobia. In posttraumatic stress disorder, a history of trauma is present and avoidance isassociated with trauma-specific cues. (See "Posttraumatic stress disorder: Epidemiology, pathophysiology, clinical


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manifestations, course, and diagnosis".)

Obsessive-compulsive disorder — Obsessive-compulsive disorder may result in significant avoidance that mayresemble agoraphobia. Determining the reasons for avoidance assists in distinguishing the disorders. If anindividual is avoiding situations for fear of triggering an obsession, then a diagnosis of obsessive-compulsivedisorder is likely (eg, avoidance of a range of public situations for fear of contamination). (See "Obsessive-compulsive disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis".)

Separation anxiety disorder — Both agoraphobia and separation anxiety disorder are characterized bysituational avoidance. Examining the focus of concern will help to distinguish these disorders. In separation anxietydisorder, fear is focused on separation from home or major attachment figures and harm befalling majorattachment figures (eg, a son worries about his mother getting into a car accident). In agoraphobia, the fear isfocused on the situation and personal catastrophe that may occur (eg, being overcome by panic or anxietysymptoms, being unable to get help if needed). (See "Overview of fears and specific phobias in children".)

Major depressive disorder — Social withdrawal and anhedonia characteristic of major depressive disordermay resemble avoidance characteristics of agoraphobia. Determining the reasons for avoidance is helpful indistinguishing the two disorders. In agoraphobia, individuals often wish they could enter a situation but feel unableto do so because of anxiety. In contrast, individuals with depression describe a lack of interest or energy thatresults in reduced engagement in activities and avoidance. (See "Unipolar depression in adults: Epidemiology,pathogenesis, and neurobiology".)

General medical conditions — Certain general medical conditions such as irritable bowel syndrome or Crone’sdisease may be associated with significant anxiety and situational avoidance. If the anxiety and avoidance areconfined to fears related to the illness, such as losing control of the bowels in the context of irritable bowelsyndrome, the fear/avoidance should be clearly excessive compared to that typically seen with these conditions.(See "Clinical manifestations and diagnosis of irritable bowel syndrome".)

Assessment tools — Comprehensive diagnostic interviews based on DSM-5 diagnostic criteria for agoraphobiaare under development. Versions based on an earlier version of the DSM are available, including the StructuredClinical Interview for DSM-IV [41] and the Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) [42]. Theseinstruments are time consuming (approximately two hours in a mental health clinical setting) and may not bepractical in a general practice setting. If a setting is focused on assessment and treatment of anxiety disorders, itis recommended that a structured diagnostic interview be used to ensure a thorough diagnostic assessment.Implementation in a team setting is also more feasible as these interviews can be administered by other healthcare professionals and then findings reviewed by the physician.

The agoraphobia subscale of the Fear Questionnaire [43] is a useful screening tool that can be easily incorporatedinto routine care.

Data suggest that a dimensional view of agoraphobia is more clinically useful than a categorical one, particularlywith regard to measuring initial symptom severity and for assessing treatment progress and outcome [44]. Thefollowing measures are recommended for treatment planning purposes and assessing treatment response:

The Mobility Inventory is a useful measure of severity, and lists 26 situations with two subscales assessingdegree of avoidance “when alone” and “when accompanied” [45].

The Agoraphobic Cognitions Scale assesses common beliefs characteristic of agoraphobia [46].

It can also be helpful to measure level of anxiety sensitivity using the Anxiety Sensitivity Index [47].

These measures can be completed outside the office and returned with the patient at the next visit. They are easilyscored and thus provide the physician with an objective indicator of symptom severity and treatment response.

TREATMENT — Although with the revision of DSM-IV to DSM-5, agoraphobia is diagnosed independently of panicdisorder, there has been little study of treatment for agoraphobia outside of trials in patients with both panicdisorder and agoraphobia. Based on current evidence, treatment of agoraphobia independent of panic disordershould follow recommendations for agoraphobia in the context of panic disorder. (See "Pharmacotherapy for panicdisorder" and "Psychotherapy for panic disorder".)


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SUMMARY AND RECOMMENDATIONS

Agoraphobia is defined in DSM-5 as anxiety about and/or avoidance of situations where help may not beavailable or where it may be difficult to leave the situation in the event of developing panic-like symptoms orother incapacitating or embarrassing symptoms. Commonly feared situations include crowds, shoppingmalls, driving, public transportation, and being away from home. (See 'Diagnosis' above.)

Agoraphobia now exists as an independent disorder in DSM-5, which may or may not co-occur with panicdisorder and with panic attacks. Agoraphobia is often a complication of panic disorder wherein agoraphobicavoidance develops in response to unexpected panic attacks and the person avoids certain situations in anattempt to avoid future attacks and/or to avoid being incapacitated and unable to escape if an attack wereto occur. Agoraphobia can develop in the absence of panic attacks; in such instances, fears about beingincapacitated or unable to cope occur in particular situations other than panic attacks. (See 'Epidemiology'above and "Panic disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, anddiagnosis".)

Agoraphobia is more common in women than men. Common comorbid disorders include other anxietydisorders, mood disorders, substance disorders and somatoform disorders. (See 'Epidemiology' above.)

A number of etiological factors have been implicated in the development of agoraphobia, including genetics,personality, cognitive factors, and social/environmental factors. (See 'Pathogenesis' above.)

There is a range of agoraphobic avoidance. In severe cases, people may become housebound. Individualsmay engage in a variety of safety behaviors to manage their anxiety when confronting feared situationsincluding being accompanied by a companion who increases feelings of security, carrying a cell phone orantianxiety medication, and sitting near an exit or door to increase ease of escape if needed (table 2). (See'Clinical manifestations' above.)

The median age of onset of agoraphobia is 20. Without treatment, the course of agoraphobia is oftenchronic and unremitting. (See 'Course' above.)

A comprehensive assessment of agoraphobia should include: (See 'Diagnosis' above.)

The focus of fear

The range of situations that are feared

Reasons for avoidance

Factors that influence the nature and intensity of the fear

The presence of safety behaviors

The presence of panic attacks and panic disorder

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Topic 15915 Version 3.0


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GRAPHICS

Common agoraphobic situations

Waiting in line

Crowds

Being home alone

Grocery stores

Shopping malls

Driving

Restaurants

Movie theaters

Wide open spaces

Hairdressing appointments

Doctor or dentist appointments

Being away from home

Public transportation

Flying


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Examples of agoraphobic safety behaviors

Travelling with a familiar person

Carrying a cell phone

Carrying medication

Carrying a water bottle

Sitting close to an exit or a door

Taking a medication prophylactically (eg, anti-diarrheal or anti-nauseant)

Carrying a paper bag (in case of hyperventilation)


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