DEPRESSION AND ANXIETY 27:113–133 (2010)
AGORAPHOBIA: A REVIEW OF THE DIAGNOSTIC
CLASSIFICATORY POSITION AND CRITERIA
Hans-Ulrich Wittchen, Ph.D.,1?Andrew T. Gloster, Ph.D.,1Katja Beesdo-Baum, Ph.D.,1Giovanni A. Fava, M.D.,2
and Michelle G. Craske, Ph.D.3
The status of agoraphobia (AG) as an independent diagnostic category is reviewed
and preliminary options and recommendations for the fifth edition of The Diagnostic
and Statistical Manual (DSM-V) are presented. The review concentrates on
epidemiology, psychopathology, neurobiology, vulnerability and risk factors, clinical
course and outcome, and correlates and consequences of AG since 1990. Differences
and similarities across conventions and criteria of DSM and ICD-10 are considered.
Three core questions are addressed. First, what is the evidence for AG as a diagnosis
independent of panic disorder? Second, should AG be conceptualized as a subordinate
form of panic disorder (PD) as currently stipulated in DSM-IV-TR? Third, is there
evidence for modifying or changing the current diagnostic criteria? We come to the
conclusion that AG should be conceptualized as an independent disorder with more
specific criteria rather than a subordinate, residual form of PD as currently stipulated
in DSM-IV-TR. Among other issues, this conclusion was based on psychometric
evaluations of the construct, epidemiological investigations which show that AG can
exist independently of panic disorder, and the impact of agoraphobic avoidance upon
clinical course and outcome. However, evidence from basic and clinic validation
studies remains incomplete and partly contradictory. The apparent advantages of a
more straightforward, simpler classification without implicit hierarchies and
insufficiently supported differential diagnostic considerations, plus the option for
improved further research, led to favoring the separate diagnostic criteria for AG as a
diagnosis independent of panic disorder. Depression and Anxiety 27:113–133,
rrrr2010 Wiley-Liss, Inc.
Key words: agoraphobia; panic disorder; classification; diagnostic criteria;
This review focuses on key critical issues pertaining
to the definition of agoraphobia (AG) and its relation-
ship to panic disorder (PD), and its future diagnostic
classificatory conceptualization in the fifth edition of
The Diagnostic and Statistical Manual (DSM-V). Starting
with an historical account of various conceptualizations
of AG and associated diagnostic criteria, we address
several core issues that are and have been controversial
since DSM-III-R.It should be noted that this
discussion also occurs in the context of several other
relevant reviews, such as the reviews on panic attack
(PA) and PDas well as Specific Phobia,which also
includes a review on the relationship between AG and
Specific Phobia. In light of these other reviews, we
only peripherally address these disorders and their
Published online in Wiley InterScience (www.interscience.wiley.
Received for publication 13 October 2009; Accepted 30 October
This article is being co-published by Depression and Anxiety and
the American Psychiatric Association.
The authors report they have no financial relationships within the
past 3 years to disclose.
?Correspondence to: Hans-Ulrich Wittchen, Department of
Psychology, Institute of Clinical Psychology and Psychotherapy,
Technische Universita ¨t Dresden, Chemnitzer StraXe 46, D-01187
Dresden, Germany. E-mail: firstname.lastname@example.org
1Institute of Clinical Psychology and Psychotherapy, Technische
Universitaet Dresden, Dresden, Germany
2Clinical Psychology, University of Bologna, Bologna, Italy
3Department of Psychology, University of California, Los Angeles,
implications for the core issues. This article was
commissioned by the DSM-V Anxiety, Obsessive–
Compulsive Spectrum, and Posttraumatic and Disso-
ciative Disorders Work Group. Recommendations
provided in this article should be considered prelimin-
ary at this time; they do not necessarily reflect the final
recommendations or decisions that will be made for
DSM-V, as the DSM-V development process is still
ongoing. It is possible that this article’s recommenda-
tions will be revised as additional data and input from
experts and the field are obtained. It should also be
noted up front that despite consensus in the Task Force
there was no unanimous consensus among all advisors
to the Task Force with regard to the conclusions
summarized in this document.
STATEMENT AND SIGNIFICANCE
OF THE ISSUES
Three core issues are addressed, most of which have
been discussed controversially in previous revisions of the
DSM revision processes.First, what is the evidence that
AG exists independently from PD in terms of its
epidemiology and the classical validators for diagnoses?
Second, should AG be conceptualized as a subordinate
form of PD as currently stipulated in DSM-IV-TR or is it
better defined as an independent disorder, as in the
International Classification of Diseases 10th revision
(ICD-10)? Finally, we also comment on how changes in
the diagnostic criteria for AG may improve precision,
reliability, and ease of administration. These questions are
considered to be particularly relevant from the perspective
of recognition, treatment, and management, because there
have been concerns that the residual status of AG and its
definition might be associated with underdiagnosis and
undertreatment. There have also been concerns that the
description of AG and the relationship of AG to PA and
PD are unnecessarily complex, making its use complicated
and possibly reducing its clinical utility. Additionally,
doubts have been expressed on whether the assumed
causal role of PA and panic-like features is a valid
assumption in agreement with empirical evidence and
whether it is needed at all. Finally, the position and
definition of AG is one of the rare examples where DSM-
IV-TR and the ICD-10 deviate from each other, leading
potentially to continued discrepancy in how these patients
are being diagnosed worldwide.
The review consists of three major sections. The first
section addresses the question of whether recent studies
provide evidence that AG exists independently from PD
and PAs. Using available evidence and selected core
publications before 1990, core questions focused on: (1)
How frequently does PD occur with and without AG? (2)
How frequently does AG occur without a history of PA?
(3) What are the characteristics of PD with and without
AG as well as AG without PA with regard to gender, age
of onset, impairment, and associated factors? In the
second section, we review available evidence with regard
to vulnerability and risk factors for AG to examine
evidence for AG being a separate construct using classical
validators. In the final section, we use this evidence to
address the question of whether AG should be con-
ceptualized as a subordinate form of PD, as currently
stipulated in DSM-IV-TR, or whether it should be
defined as an independent disorder.
It should be noted upfront that changes in the DSM
nomenclature and/or the use of ICD criteria have
partially resulted in corresponding changes in diag-
nostic assessment instruments used for research stu-
dies. Such changes and the use of different diagnostic
criteria complicate considerably the interpretation of
research findings and the conduct of this systematic
review of AG. At the very least, results from different
studies must be interpreted in light of whether DSM or
ICD diagnostic rules were utilized. At worst, results
from different studies and across different versions of
the manual are rendered incomparable. Given this
limitation and considering the length of manuscript,
this paper could not fully appreciate in detail several,
undoubtedly important, clinical distinctions surrounding
the expression of agoraphobia and its measurement.
HISTORICAL PERSPECTIVE OF
AGORAPHOBIA IN REVISIONS OF
THE ICD AND DSM
The first account of AG is creditedto Westphal’s
classical description (1871) of the syndrome that,
during the major part of the last century, served as a
model paradigm for anxiety disorders in general.
From that time until the introduction of DSM-III-R,
AG was frequently described and reported in the
literature as a common and distressing phobic disorder,
or as phobic neurosis in the older literature.[4,7,8]
Internationally, AG was introduced and codified as an
independent diagnostic entity and distinctive syndrome
of multiple fears in the 1970s (ICD-9),where it
retains this status even today (ICD-10).In the
United States and the DSM system, AG also appeared
as the result of subdividing phobic neurosis and anxiety
‘‘marked fear and avoidance of being alone or in public
places from which escape might be difficult or help not
available in case of sudden incapacitations’’ did not
differ much from that of other phobic disorders in
DSM-III and the ICD definition of AG. The text
description in DSM-III, however, already stipulated in
1980 that the diagnosis of AG is more closely linked to
PAs than to phobias. ‘‘Agoraphobia with Panic Attacks’’
should be coded if ‘‘the initial phase of the disorder
consisted of recurrent panic attacks,’’ thus leading the
individual to develop anticipatory fear of having such
an attack and to avoid situations associated with these
attacks. Only when there was no history of PA (or the
information was lacking), the diagnosis of ‘‘Agoraphobia
without Panic Attacks’’ was made.
114 Wittchen et al.
Depression and Anxiety
Starting with DSM-III-R—and unlike the ICD-9—
AG was specifically defined as a classically conditioned
response to situations in which PAs had occurred. In
responseto increasing experimental
evidence,[12–17]AG in DSM-III-R was not only con-
ceptually attached to PA and PD, but was also seen
explicitly and exclusively as a temporally secondary
complication. In fact, with each consecutive DSM
revision, the residual status of AG within the construct
of PA and PD has been increasingly more pronounced.
DSM-IV-TRacknowledges the relevance of AG as a
syndrome by describing criteria that state upfront that
AG (in itself) ‘‘is not a codable disorder.’’ Instead,
allowances are made and codes provided for those
disorders in which AG occurs, namely PD with AG or
AG without the History of Panic Disorder (AG w/o PD).
The latter, however, restricts the diagnosis to those
patients where AG is related to fear of developing panic-
like symptoms (e.g., dizziness or diarrhea). The DSM-
IV-TR formulation results in a fairly complex (12 pages)
differential diagnostic scheme with lengthy differential
diagnostic considerations. Unlike all other disorders, two
core psychological syndromes, namely PAs (that may
occur in the context of many mental disorders) and AG
(only relevant for PD and AG w/o PD), are described
first before the specific diagnoses are described.
This procedure has deepened discrepancy between
DSM and ICD. The ICD-9 and the ICD-10 do not
assume that AG necessarily arises from PAs, and thus
have retained AG as a separate disorder, independent of
PD. Furthermore, in the DSM-IV-TR, the definition
of AG is substantially different from the definition used
for other phobic disorders in that the diagnostic criteria
for AG are tied not only to the concept of PA or PD
but also to ‘‘panic-like symptoms’’ (AG w/o PD). This
conceptual development in DSM was based mainly on
the observation in some studies[15,19,20]that among
clinical samples in research settings in the United
States, that use DSM-III-R criteria, AG patients
without PAs or panic-like features appear to be
extremely rare—an observation that continues to
date.Fava et al.attributed this largely to the fact
that the diagnostic criteria and assessment instruments
are by now so ‘‘biased’’ toward the temporally primary
causal role of PAs or panic-like features that it is
impossible to diagnose AG outside the context of
primary PAs or panic-like features. Thus, to date, the
implicit hierarchical criteria in DSM-IV have rendered
it impossible to collect systematic data to resolve this
issue, if one sticks strictly to the current DSM-IV-TR
definition. The lack of resolution has led to the
unfortunate situation of two discrepant diagnostic
criteria sets worldwide, and use of different criteria in
different diagnostic interviews. This makes direct
comparisons of findings in this domain difficult and
in some areas impossible.
It is important to note that in contrast to the
definition of AG and the assumed causal role of PA or
panic-like features, there is no to little controversy
regarding the diagnostic criteria of PA or PD or the
fact that both are frequently comorbid with AG. Further,
both positions agree that, by and large consistent with
the classical literature, that PA and panic-like features
may play a core role in the development of some but
not all AG patients.[7,22]The disagreement mainly
surrounds whether (a) AG exists at all independent of
initial primary PAs or panic-like features,[23–33](b)
whether PA or panic-like features are invariably
causally linked to AG, or (c) whether there is any
clinical utility in diagnosing AG as a separate
disorder,[34–37]and (d) whether at all and if yes how
to define and specify the explicit criteria for AG in a
better way.[37–39]Further, some uneasiness has been
expressed as to whether the DSM-IV-TR conceptua-
lization of AG as a residual of PD (AG without the
history of PD) is in line with the overarching principles
of DSM-III and its successors to be atheoretical and
descriptive unless persuasive aetiopathogenic mechan-
isms have been established. Although such persuasive
evidence is lacking, DSM-IV-TR’s explicit diagnostic
hierarchy rules assume such an etiological role of PA
and PD for AG, resulting in a near unconditional
priority of PD over the diagnosis of AG.
To summarize, since DSM-III-R, AG is diagnosed
only within the context of PD (PD with AG) or as the
result of PA or panic-like features (AG without a
history of PD). This convention is in contrast to the
ICD-10, where AG in fact takes precedence over PAs,
and prior diagnostic conventions in DSM-III, where
AG was defined similar to phobias.
Another unresolved question is how to diagnose
patients who fail to report panic-like symptoms as
required by DSM-IV-TR. Assuming that such cases
might exist, should such cases be diagnosed as anxiety
disorder NOS or as a specific phobia in DSM? This
issue has been identified as particularly critical by
developers of diagnostic interviews and epidemiologi-
cal research.[26,40]The current DSM-IV-TR provides
little guidance in this respect, which constitutes a
potential problem. Unlike phobic disorders, where
separate criteria are specified, the current ‘‘broad’’ AG
definition lacks specification for what constitutes
agoraphobic situations and cues beyond the occurrence
or fear of panic-like symptoms. Further, unlike phobic
disorders, AG criteria do not specify the additional
mandatory criteria for phobic disorders, such as the
‘‘exposure’’ criterion (B), the criterion that the person
recognizes his fear as excessive or unreasonable (C), or
the distress and impairment criterion (E). As stipulated
in the ICD-10 criteria for research,AG should be
diagnosed when the AG syndrome occurs in at least
two out of a total of four prototypical situations to
qualify for what is called in both systems as ‘‘a
characteristic cluster.’’ In response to this, most recent
diagnostic interview versions assign the diagnoses
whenever two or more situations are endorsed. Because
DSM-IV-TR lacks such a precise definition, numerous
and mostly older DSM studies assigned the diagnoses
115 Review: Agoraphobia Review
Depression and Anxiety
even when only one situation is endorsed and without
additional mandatory criteria used for all phobic
disorders (Social Phobia or Specific Phobias).
Beyond these core issues, revisions of DSM-III have
added some modifications of the diagnostic specifica-
tion of AGthat were critically reexamined. In the
DSM-III-R,an AG diagnosis was assigned when the
person was anxious about having a PA that s/he
restricts travel (avoidance), needs a companion to
travel (use of companions), or endures AG situations
despite intense anxiety (distress). These criteria have
been criticized as lacking proof of incremental validity
and being overinclusivebecause they do not restrict
AG to exhibiting avoidance behavior. That is, patients
might be able to travel extensively even though they
need a companion to do so, or they might even be able
to travel alone while experiencing significant distress.
Further, DSM-III-R delineated situational avoidance
as the central issue to be considered by classifying AG
across four different levels (none, mild, moderate,
severe). In the DSM-IV,[18,41]this is no longer the case
with situational avoidance on equal footing with
distress and use of companions in making a dichot-
omous AG diagnosis (absent, present). This has been
criticized by Schmidt and Cromeras potentially
decreasing clinical utility as well as predictive value,
because situational avoidance has been de-emphasized
in making AG diagnosis. Further, the reduction of
specification of AG from a dimensional AG 4-point
rating to a dichotomous (present/absent) approach
suggests that a dichotomous method of organizing
agoraphobic behaviors is superior to the more finely
graded assessment of phobic avoidance. However, no
data have been presented to support this. Schmidt and
Cromerassumed that this decision might have
reduced the clinical utility of an AG diagnosis.
Given these controversies and unresolved issues, this
article was commissioned by the DSM-V Anxiety,
Obsessive–Compulsive Spectrum, Posttraumatic, and
Dissociative Disorders Work Group to review this
critical issue again, to explore whether new data allow a
resolution of these issues.
METHODS OF LITERATURE
SEARCH STRATEGY AND SELECTION
We searched the ‘‘Web of Science,’’ ‘‘PubMed,’’ and
‘‘PsychINFO’’ databases in April 2008 for peer-
reviewed articles on AG, and updated the review in
March 2009. Reference lists of retrieved articles were
searched for additional studies. Only articles in English
and German were considered, and over 30 search terms
were used (full list available on request). Articles on AG
printed after 1990 were targeted, but compelling
articles published before 1990 were also included.
Articles were selected if they were peer-reviewed and
addressed issues of epidemiology, therapy, experimen-
tal procedures, neurobiology, psychopathology, diag-
nosis, or assessment. The DSM-IV Source Bookand
DSM-IV Options Bookwere also reviewed.
DATA COLLECTION AND ANALYSIS
The method section of each study was examined first
with respect to its assessment/diagnosis of AG. Studies
that examined AG independent of PA and PD were
marked and selected for priority review. Given the
paucity of such studies, quantitative analysis of results
was rendered impossible. As such, articles that utilized
hierarchical DSM-IV rules were also considered.
Studies were further grouped according to the follow-
ing thematic areas: prevalence and incidence, develop-
mental issues and age of onset, natural course and
outcome, patterns of co-morbidity and transition
between disorders, vulnerability and (causal) risk
factors, including genetic and family genetic factors,
temperamental antecedents, cognitive and emotional
processing abnormalities, neural substrates and shared
biomarkers, and treatment/treatment response.
DESCRIPTION OF STUDIES/
METHODOLOGICAL QUALITY OF
All search terms and databases revealed a total of
2,112 citations, 469 of which were judged relevant for
this review. Of these, less than 5% assessed AG
independent from present DSM hierarchical rules.
Findings from studies tied to the current DSM cannot
inform about the independence of the diagnosis or its
relation to specific phobia or PD. The overall
frequency of relevant articles per thematic topic was
as follows: Conceptualization (n521), Relationship
between AG, PA, PD, and Specific Phobia (n566),
Co-morbidity (n547), Transition between disorders
(n521), Temperament Antecedents (n519), Cogni-
Vulnerabilities and Risk Factors (Environmental and
Genetic) (n557), Familiality (n526), Developmental
Patterns (n522), Assessment Complications (n527),
(n520), Symptom Similarity (n59), and Treatment
RESULTS OF REVIEW
EPIDEMIOLOGICAL AND CLINICAL
EVIDENCE FOR AG
Since 1980s, a wide range of commu-
nity studies in the United States,[43–46]Europe,and
the rest of world[48–52]have examined the lifetime and
12-month prevalence of PAs, PD, and AG, according
to the criteria of DSM-III, III-R, and IV. Despite some
variation in lifetime prevalence estimates, they almost
all converge on the following: (a) PAs according to
116Wittchen et al.
Depression and Anxiety
DSM-III-R and IV are very frequent manifestations
with estimates of 20% or above for most samples, (b)
lifetime rates of PD are in the range of 3–5%;
depending on the study, approximately 35–65% of
subjects with PD meet criteria for PD with AG,
whereas the remaining report PD without AG, and (c)
rates for AG without history of PD are typically found
to be at least as high or even higher as those for PD.
However, they also reveal a large degree of variation of
prevalence across studies, ranging from about 1% to a
high of 22% (median for older and more recent
199053.8%), probably due to methodological factors.
AG without PD have been reported to occur in both
childrenand in the elderly.
A recent review by Faravelli et al.summarized five
epidemiological studies that convergently found that
46–85% of all individuals with AG do not have PAs. He
also showed, however, that in clinical samples (eight
studies mostly with a few dozen patients), AG without
PA is considerably less frequent (0–31%), with four
studies finding not a single case. In studies published
since 1990,[45,55,56]which used a stricter definition of
AG requiring at least two agoraphobic situations
consistent with ICDs and DSMs stipulation of a typical
‘‘cluster’’ of situations, the 12-month rates for PD with
and without AG was found to be 1.8% (interquartile
range [IR]: 0.7–2.2) and 1.3% (IR: 0.7–2.0) for AG
without PAs. The variation between studies has been
attributed to design, methodological, and assessment
variation rather than reflecting true differences; for
effects.[47,55]An important example of such a metho-
dological factor is the different conventions used for
the DSM-IV ‘‘A’’ criterion. In contrast to studies in the
1980s with the Diagnostic Interview Schedule (DIS),
where even one single AG situation may qualify for a
diagnosis, most recent studies using the Composite
International Diagnostic Interview (CIDI) required
two or more situations to meet criteria for DSM-IV-TR.
This change led to decreases in rates of AG by
approximately 50%. It also affected the rates for PD
with AG, revealing now—in contrast to older studies—
more cases of PD without AG than PD with
To summarize, consistent with a previous review of
this issue by Ballenger and Fyer,the prevalence of
AG without a history of PD and even the prevalence of
AG even without the presence of PA and panic-like
symptoms (as is possible in the CIDI/ICD-10) was at
least as high as the combined rates of PD with and
dies.[33,45,56–61]Thus, even when conservative defini-
tions are utilized (i.e., strict reliance on DSM-IV-TR
criteria), as in the most recent NCS-R findings,[45,62]
roughly 25% of all subjects with panic/AG syndromes
met AG criteria without qualifying for either PAs or
PD. Therefore, persuasive evidence has documented
substantial rates of AG without PD and without PA in
of culturalor regional
the community that are approximately as frequent as
those that occur concurrently with PD.
According to US studies, the situation in clinical
settings appears to differ. As reviewed by Ballenger
and Fyerand Barlow,[19,20]at least the diagnosis of
‘‘AG without the history of PD’’ is rarely assigned in
clinical practice. Faravelli et al.reviewed eight
clinical studies, seven with low sample sizes, citing
four studies with not a single case of AG without
panic and four studies reporting 2–31% of PA among
Temporal relationship of PA, PD, and AG.
studies used longitudinal data to specifically examine
the question of whether AG is always related to pri-
mary spontaneous PAs or at least panic-like symp-
toms.[21,26,28,33,40,63]Consistent with other evidence
from similar inquiries in epidemiologicaland clinical
samples,[32,64,65]these explorations found no consistent
evidence to support these assumptions. In community
samples, the majority of agoraphobics never experienced
any PA or panic-like symptoms or psychophysiological
symptoms of other type that clearly preceded the onset
of agoraphobic avoidance. If they reported such
symptoms, they were frequently secondary to AG onset,
and longitudinal evidence suggests that AG just as
frequently precedes PA as PA precedes AG.
Mostly smaller (less than 70 patients) clinical studies
in the United States[17,66,67]find that in the vast
majority of patients with AG/PD or AG with PA,
agoraphobic avoidance clearly occurs temporally sec-
ondary to the PA. Ballenger and Fyerconcluded after
examination whether primary PAs also affect the
natural course of secondary AG that, although agor-
aphobic avoidance does not seem to be related to
variables, such as type of PA frequency or severity of
attacks, it does seem to be related to the expectation of
panicking in specific AG situations. However, these
findings do not imply that ‘‘panic expectancy is of
causal significance for the development of agoraphobia
avoidance’’ (Ballenger and Fyer,p 455).
Other lines of evidence for inconsistent findings
come from clinical retrospective studies that used
sensitive methods to detect subclinical symptomatol-
ogy prior to the onset of PAs. Fava et al.found that
the majority of 40 patients with PD with AG
experienced prodromal symptoms (AG, hypochondria-
sis, generalized anxiety) before the first PA. The
findings were obtained with considerable methodolo-
gical precautions: careful dating of symptom onset,
rigorous symptom definition by a reliable and validated
probe suitable for prodromal and subclinical symp-
toms, and delay of the interview until the acute
disturbance has passed (to minimize distortions of
recall). These methodological features may account for
the striking differences from studies performed in the
mid-eighties, which relied on self-rating instruments,
unstructured interviews, and diagnostic instead of
symptomatic focus. Not surprisingly, the findings were
confirmed by subsequent studies. Garvey et al.
117 Review: Agoraphobia Review
Depression and Anxiety
found that 28% of 32 PD patients had prodromal
symptoms of anxiety that lasted a median of 5 years
before the occurrence of the first PA. Lelliott et al.
reported that 70% of 57 patients with PD with AG had
prodromal depression, anxiety, or avoidance. Agora-
phobic avoidance preceded the first PA in 23% of
patients. Argyle and Rothconsidered the sequence of
the events in 56 cases of PD associated with AG. They
found that the majority of patients (55.4%) had their
onset in the same 6-month period as the onset of PD,
with 19.6% of patients for whom an AG clearly
preceded panic and 25% of patients with the reverse
sequence of events. Other diagnoses, especially social
phobia and generalized anxiety disorder, however,
frequently predated the onset of panic. In the same
vein, long-standing hypochondriasis was found to
precede the onset of PAs not associated with AG.
Perugi et al.studied 126 consecutive cases of PD by
means of semi-structured interviews and substantially
replicated the findings of Fava et al.Further, in
several studies,[32,70,71]the large majority of patients
experienced their first PAs in public places and
This considerable degree of discrepancy in findings has
not yet been resolved because of methodological problems
inherent in studies. But it could be at least summarized;
there is fairly consistent evidence that PA precedes AG in
up to 50% of all individuals with AG, providing some
support for the assumed aetiopathogenic pathway implied
in DSM-IV-TR. However, the fact that up to 50% of AG
does not reveal indications for this pathway is suggestive
of the existence of other pathways. It should also be noted
that these data are not fully consistent with the
panic–agoraphobia spectrum concept[72,73]that assumes
a reciprocal relationship, meaning that either condition
raises the probability of the other one. The epidemiolo-
gical evidence does not support this reciprocal relation-
ship. A major limitation of these studies is that the
majority of them rely heavily on retrospective reports
about the onset of each condition. Further, subjects were
studied sometimes decades after onset, making retro-
spective appraisals highly problematic. This problem
becomes easily apparent when examining age of onset
reports for PAs and AG onset, reviewed below in a
Prospective longitudinal investigations in well-defined
age groups might resolve such issues, but are rare. In fact,
we found only one recent prospective longitudinal multi-
wave study that systematically described incidence char-
acteristics of PA, PD, and AG.This prospective study
found that 23.5% with an initial PA subsequently
developed AG, as did approximately 50% developed
PD. This constitutes a 17-fold risk increase for developing
AG and a 38-fold risk for PD. It should be noted, though
that PAs were highly associated with all types of disorders,
including other anxiety, mood, and substance disorders,
and thus are not very specific for either AG or PD.It is
also noteworthy that cases with temporally primary AG
(without PA according to DSM-IV-TR or even panic-like
features (as defined by ‘‘fearful spells’’) were not at
increased risk for subsequent PA or PD; only 11.6% of
all primary AG developed a subsequent PA and only 2.4%
Critical methodological aspects.
epidemiological studies to support the assumption that
PAs and panic-like symptoms almost always play a core
pathogenic role for the onset of AG has been repeatedly
challenged on methodological grounds. Against the
background of observations that AG without PA/PD is
rarely seen in clinical samples,[15,19,20]methodological
concerns were raised that current diagnostic instruments
might not be able to assess panic features with sufficient
accuracy and validity, or more generally, that the
diagnostic interviews were not diagnostically valid.
Horwath et al.and Goisman et al.conducted
careful clinical reappraisals that, however, were based
only on a few dozen patients. In response, Wittchen
et al.conducted a careful clinical reappraisal of all AG
cases in the Early Developmental Stages of Psycho-
pathology (EDSP) data set. The clinical appraisal of each
case was conducted by independent clinicians who were
blind toward the interview diagnosis. The outcome of
this appraisal (based on clinical questions like ‘‘What are
you afraid of?’’) failed to raise any doubts that these cases
were AG cases, without indications of prior PAs or
panic-like symptoms whenever the diagnosis was based
on at least two out of a total of five (plus ‘‘other’’)
agoraphobic situations were met. The reappraisal also
indicated that cases meeting all criteria, but only
reporting one of the prototypical situations, were often
better reclassified as specific phobia, mostly of situational
type. Similar evidence was also provided by Faravelli
et al.and Fava et al.The publication of the studies
in the 1990s led the CIDI criteria to be changed. They
now require at least two situations to be reported before
assigning a diagnosis of AG; cases below this threshold
are classified as phobia NOS. It should be noted that this
change in the diagnostic interview reduced substantially
the rates of AG in general, as well as the rates of PD with
AG. This algorithmic change is also responsible for the
decline in rates of AG in more recent studies since the
1990s. It should be noted though that despite the
considerable sophistication in such methodological
appraisals, some task force advisors still believe that
methodologically sound, and full appreciation of all
critical concerns is still lacking.
How frequent is AG without panic attacks or
Based on these revised, more stringent AG criteria
and a careful prospective longitudinal investigation about
the relationship of PAs and PD with AG, Wittchen et al.
conducted a comprehensive analysis of the incidence
patterns and temporal relationship of mutually exclusive
classes of various liberal definitions of panic-like features
(labeled fearful spells) in a sample of 3,021 subjects.
This longitudinal characterization (see Fig. 1)
of AG without any indications of even the most liberally
defined fearful spells is 1.5%. This rate is approximately
The failure of
118 Wittchen et al.
Depression and Anxiety
the same rate with which PD without AG occurs. In
addition to AG without fearful spells (1.5%), 1.3% of
cases report fearful spells after the onset of AG. The
strict DSM-IV-TR definition of AG without a history of
PD is only met by 0.6%, whereas the rate of PD with
AG is 1.9%. Along with other information and
transitional analyses, this study concluded that AG is a
clinically significant disorder that may exist indepen-
dently from PA and PD in a substantial proportion of
subjects. This exploration also shed light on a second
problem inherent in DSM-IV criteria and diagnosis of
PD and AG, namely that the subjects in the population
without PA and PD remain undiagnosed because of the
DSM stipulation that AG syndromes occur in response
to panic-like symptoms. As documented in this study, a
substantial number of subjects fail to report or
experience any such symptoms.
Gender and age of onset of PA, PD, and AG.
stronger female preponderance was found for AG
without panic than for PD.[47,77]To our knowledge,
there are no studies that have reported significant
age?gender interaction differences between PD and
AG. Age of onset characteristics of PAs as well as PD
with and without AG are well studied and suggests little
differences. According to retrospective cross-sectional
community studies covering ages 181, all three groups
reveal a mean age of onset of 21–23 years with overall
strikingly similar age of onset curves.As a function
of different sample composition, some studies reported
slightly higher ages (23–36).[48,78,79]The studies con-
sistently show that two thirds of all PD cases develop
before age 35, with a substantial incidence risk in late
adolescence and rarely in childhood.There are some
indications for a bimodal high risk distribution for PAs,
with one peak around ages 15–19 and another one at
higher ages (35–50).[59,81–83]Some studies suggest that
the presence of AG seems to affect the age of onset of
PD with some inconsistent indications for a later age of
onset.[35,84]Overall, age of onset characteristics of AG
without PA are less well established. Among those
specifically addressing AG without PAs, a slightly later
mean onset of AG was shown, ranging from 25–29
years of age,[59,78,83,85]with some indications for a
bimodal distribution (second high incidence period
after age 40) regarding onset risk. This is only partially
consistent with other findings that indicate that AG
may occur as early as childhood in greater frequency
Figure 1. Modified from Wittchen et al., 2008.The prevalence and mutually exclusive combinations of fearful spells (FS), DSM-IV-
TR panic attacks (PA), DSM-IV-TR panic disorder (PD), and Agoraphobia (AG) as assessed with the M-CIDI in the community.
Numbers indicate the number of cases and the weighted prevalence estimate.?The definition of agoraphobia is only partially (namely
for subsets of those with PD with AG, as well as AG w/o PD (but with PA)) consistent with the DSM-IV-TR criteria of either PD with
AG or ‘‘Agoraphobia without history of PD.’’ AG/FS cases meet all AG criteria, but despite fearful spells no ‘‘panic-like symptoms.’’ AG
w/o FS report not even fearful spells. The latter two groups would not be diagnosed as AG according to DSM-IV-TR.??Subjects with
fearful spells (FS) have acknowledged the CIDI question: ‘‘Have you ever had an attack of fear or panic, when all of a sudden you felt
frightened, anxious or uneasy? Some people call this a panic attack.’’ They failed, however, meeting the criteria of PA, for example by not
reporting any or only an insufficient number of symptoms or by denying that the attack occurred out of the blue.
119Review: Agoraphobia Review
Depression and Anxiety
To summarize, despite some differences between AG
without PAs and PD with AG, the size of the
differences and the extent of evidence is not sufficient
to conclude that age of onset characteristics of AG
differ substantially from those observed for PD.
The few available studies,[33,62,86]
which have directly compared differences in impair-
ment and disability between PD with and without AG
and AG (without PAs or panic-like features), consis-
tently find greatest impairment for those with PD/AG
and lowest impairment for those with PAs without
meeting criteria for either disorder, with PD (without
AG) and AG (without PAs or panic-like features) in
between. It is noteworthy that PD without AG has
significantly fewer impairments than PD/AG in all
available indices (i.e., role functioning, work produc-
tivity, disability days, Panic Disorder Severity Scale,
Sheehan Disability Scale) and does not differ from the
impairment observed for AG without panic.It
should also be highlighted that these findings are
consistent with findings suggesting that the degree of
AG seems to be a more potent determinant of disability
than number and severity of PAs.This seems to
suggest that (a) with the exception of PA, all three
conditions are quite impairing disorders, with PD/AG
cases revealing the most severe expressions, (b) AG
without PAs is as impairing as PD without AG, and (b)
that AG in PD patients considerably worsens function-
ing and degree of disability.
Helpseeking and treatment.
examined help-seeking rates for all three conditions
considered. Wang et al.reported for the United
States that PD (41.2%) and AG without PD (42.1%)
rank among the mental disorders having most fre-
quently received ‘‘at least minimally adequate treat-
ment.’’ However, AG without PD differs substantially
from PD patients in that they received less treatment
by psychiatrists and the general health care sector.
Similar results were reported from a comprehensive
analysis of 14 European Union studies.The lower
rates for AG cases in psychiatric and general health
care are consistent with clinical observations that such
patients are rarely seen in specialized care.More
detailed analyses by Noconin Germany further
reveals that professional help-seeking among those
with PD/AG and those with AG with PA occurred
significantly more often because of panic problems
than AG problems. It should be noted, however, that
such patterns depend heavily on characteristics of the
health care system. For example, AG without PA in
Germany is predominantly seen by psychotherapists,
whereas PD is more frequently seen by psychiatrists.
Kessler et al.reported similar indications for the
United States, although they were not statistically
sistent evidence that salient correlates differ across the
tion. Namely, individuals who have AG without PA
Few studies have
There is no con-
and PD/AG are noticeably more frequently unem-
ployed and disabled than individuals without AG.[26,45]
allow for direct comparisons of co-morbidity patterns
in community samples. There is agreement, however,
that PD and AG both are rarely seen in pure forms and
both are significantly associated with many other
diagnoses, including other anxiety, mood, substance,
and somatoform disorders.[54,56,62,90–92]Direct com-
parisons reveal higher co-morbidity rates with depres-
sive disorders for PD/AG (52%) and AG with PA
(52.3%) than those who have AG without PA (33.1%).
Thus, PD/AG and AG with PA are similarly strong
predictors for increased depression risk. Co-morbidity
with other anxiety disorders was found to be in the
same range for all groups (49–64%), with no significant
differences, though AG without PA appeared to be
more comorbid with other phobic disorders. In terms
of transitions from one syndrome to another, a number
of authors[26,74,93]have highlighted that temporally
primary PAs are a sensitive marker of subsequent
psychopathology (over 90% developed at least one
mental disorder), but not necessarily specific for PD,
AG, or other anxiety disorders.Similarly, high
associations were found for mood disorders, psychotic
disorders, and substance use disorders. In contrast, AG
is more closely and specifically linked to anxiety
disorders (highest probability) and secondary depres-
Summarizing the available evidence from epidemio-
logical studies in the community with regard to
associated factors in PD, PD/AG, and AG, there seems
to be considerable evidence that AG without PAs and
even panic-like features exists and reveals similar
impairment and disability findings as PD without
AG. Overall PD/AG seems to be the most impairing
conditions. Beyond some indications for minor differ-
ences in the other factors considered, there is little
persuasive evidence for the existence of major differ-
ences between AG without PAs and PD. Co-morbidity
analyses, however, reveal that AG appears to be more
specifically linked to other anxiety disorders and
phobias in particular, whereas PA and PD are
associated with a broader spectrum of comorbid
Few studies exist that
VULNERABILITY AND RISK FACTORS
In the next section, we will consider evidence for
differences between PD and AG without PA in
vulnerability and risk factors as well as selected clinical
Genetic and familial factors.
able evidence for the familial aggregation of PD from
various types of clinical and family studies. Studies
fairly consistently show higher rates of PD in all first-
degree relatives[95–97]of PD patients as compared to
controls. Hayward et al.suggest that parental
There is consider-
120Wittchen et al.
Depression and Anxiety
history of PD/AG may have a core role in the
development of PAs in offsprings. However, one should
caution this conclusion because PA and PD also
increase the morbidity risk of offsprings for a whole
broad range of other disorders.[99,100]Nevertheless, the
handful of studies that accounted for other disor-
ders[95,101–104]suggest that there is at least some
specificity for PD/AG. Only a few studies examined
whether there is a differential familial aggregation of
PA/PD and AG. Harris et al.found that the
increased risk of relatives of agoraphobic patients is
not confined to AG (33% vs. 15% in controls), but also
for PD (32%) and other phobias. In contrast, Smeraldi
et al.reported an increased risk only for AG and
not for PD. Further, Tsuang et al.reported that AG
among those with PA is familial, yet AG in twins is not
associated with increased PD aggregation, suggesting
that AG and panic liability are not positioned on an
agoraphobia-panic continuum. Nocon et al.found
that PD and AG aggregate in families; AG without PD
is not familial but it might enhance the familial
transmission of PD. Both parental AG and PD
similarly increase the risk in offspring to develop any
Heritability has been estimated to be 43–48% for
PD[110–112]and 61% for AG.[112,113]Kendler et al.
estimated for phobias among females a high heritability
(40–60%), suggesting a ‘‘phobia proneness’’ with AG
revealing the strongest and most specific associa-
Molecular genetic strategies have been used extensively
in PD (reviewed in) and have identified a wide
range of candidate genes and suggested mechanisms
related to neurobiological and pharmacologic targets,
most of which remain controversial: Locus coeruleus
(5HT-1A, 5HT-2C, 5HTTLPR), Katechoalminsystem
(MAO-A, COMT), Neuropeptide (NPY Y1, Y2, Y5),
Adenosinreceptors (ADORA1, ADORA2a), and CCK
(e.g., CCKAR).[116,117]In addition, there is a wide
range of studies that conducted genomewise scans
without any clear replicated candidates. More impor-
tantly, there are only very few studies that specifically
separate PD and AG. Politi et al.reported no
association between Glyoxalas-1-Polymorphisms and
PD/AG, unless they exclude AG cases. Rothe et al.
reported differential findings with regard to the 5HT
Transporter polymorphism for PD with and PD
without AG. Hettema et al.reported association
with the COMT-gene for females in PD and AG.
To summarize, there is little evidence for diagnosti-
cally specific genetic mechanisms in either PD or AG;
nor is there sufficient evidence for different mechanism
Other neurobiological factors.
chophysiology and neuroendocronological mechanism of
panic-agoraphobia are well studied (see reviews:[120–122]),
including studies in the context of panic provocation
tests (see reviews by[123–128]), to our knowledge there
Although the psy-
have been surprisingly few studies that examined
differences between PD, PD/AG, and AG without
panic. A notable exception is a study by Garvey and
Noyesthat directly and specifically examined whether
PD and AG are variants of the same disorder or distinct
diseases by laboratory measures. They examined 91 AG
patients, without specifying though the existence of
PA and 24 PD patients in terms of levels of the urinary
lysomal enzyme NAG that has been discussed to
be a marker of serotonin binding and metabolism.
This study revealed that NAG levels were signifi-
cantly lower in patients with PD as compared to AG,
providing limited support that PD and AG may be
Most studies in patients with PD
and AG describe the family climate or child rearing
behavior as being characterized by reduced warmth and
increased overprotection.[89,130–133]This relationship
is best established for PD,[132,134,135]but this factor
has been rarely considered specifically in studies with
AG without PAs. Some indication for specificity has
been reported by Kendler et al.who showed that
AG, but not PD, in females was significantly asso-
ciated with parental lack of warmth, overprotection,
Critical life events.
There is evidence that negative
events in childhood (e.g., separation, death of parent,
etc.) are associated with both AG and PD.[114,137–141]
Increased rates of critical life events have been associated
with the onset of various disorders, with little evidence
for diagnostic specificity.[141,142]However, few studies
suggest that early death and separation was associated
with PD, while only death (not separation) was
associated with AG.[114,143]
evidence that AG and PD nor any other anxiety disorder
reveal differences in the structure and frequency of
life events over the life span; all conditions were
increased when significant life events were (retrospec-
to all anxiety disorders, behavioral inhibition and neurotic
disposition (i.e., neuroticism, negative affect, anxiety sensi-
tivity) are associated with AG, phobic disorders, PD, and a
range of other conditions. Overall, there is little convergent
evidence that these dispositional measures are diagnostically
specific. Behavioral inhibition has been shown cross-
sectionally and prospectively to be associated with many
AG.[140,142,150,151]Similarly, neuroticism[79,152]and negative
affect[153–155]confirmed this association with little to no
evidence for differences. It should be noted, however, that
specific tests between PD, PD/AG, and AG without PAs
were not conducted.
A notable exception is anxiety sensitivity, or the trait
to disposition to believe that symptoms of anxiety are
harmful, as measured by the Anxiety Sensitivity Index
(ASI). A review by Hirshfeld-Becker et al.suggests
that the ASI is a specific predictor for PD but not for
other anxiety disorders. However, Hayward and
Similarly, there is no
121 Review: Agoraphobia Review
Depression and Anxiety
Wilsonfind that the ASI also predicts AG without
the presence of PA.
To summarize, the distinction between PD, PD/AG,
and AG without PA has been rarely specifically addressed
in studies on vulnerability and risk factors. Due to design
and assessment problems, there is no conclusive evidence
that reliably informs us about differences among these
conditions. The same, however, also applies to the direct
examination of differences between other anxiety and
mood conditions. Increased research on diagnosis-
specific vulnerability, risk factors and possible interac-
tions may reveal specific risks.
convergent evidence from studies that AG—measured
with various instruments—is a reliable construct that
appears in virtually all taxometric investigations as one
of the major classes.[38,87,158–162]It has been repeatedly
associated with social role impairments and clinical and
which this has been found in the context of PD led
some to suggest that AG is an indicator of severity for
PD.[56,167]Using AG indicators from various sources,
Slade et al.examined the latent structure of AG in
patients with PD and PD/AG and a community
sample, and identified an underlying dimensional
structure that suggests AG should be best conceptua-
lized as a continuum of avoidance. Although this study
did not include a group of AG without PA, it adds to
our knowledge of AG as an important construct.
Another interesting exploration by Schmidt and
Cromerhas suggested that an AG specifier provides
meaningful information regarding the expression of
PD, specifically with regard to social functioning
impairment and total distress experienced.
An important finding from this reportis the clear
suggestion that the highest level of clinical utility might
be achieved by reverting to a dimensional measure that
is specific to situational avoidance (vs. distress or use of
companions). Among the different outcomes that were
assessed, avoidance, and in particular the dimensional
measure of avoidance, consistently explained the most
variance beyond that accounted for by overall severity,
the three core panic variables (frequency, intensity, and
worry) and DSM-IV AG diagnosis. These data provide
some further indirect support for the importance of
AG, particularly in terms of greater clinical utility.
Although this exploration does not address the
independent diagnostic status of AG, it suggests that
evaluating the level of situational avoidance would also
avoid some of the criticism of the expanded criteria
AG,and might also improve diagnostic reliability
toward the use of avoidance (vs. distress and use of
companions). Although situational avoidance appears
to have important clinical utility in the context of a PD
diagnosis, it is not clear why this is the case. Feldner
et al.found that patients with PD utilize more
mately view these strategies as more effective, when
The consistency with
coping strategies are associated with higher levels of
anxious responding and increased distress in res-
ponse to bodily sensations.[168,170]Thus, it may be
that underlying cognitive or psychological factors
(e.g., coping style) dispose certain PD patients to
develop AG. If this is the case, these underlying factors
may help account for the clinical utility associated with
Clinical course and outcome.
of PD and AG in clinical and epidemiological samples
have been reported as being chronically persistent (AG)
and chronically recurrent (PD).Emmelkamp and
Wittchenfound that AG without panic ranks among
the most persistent disorders over a period of 10 years
follow-up, with a homotypic continuity greater than
the one found for PD. They also reported that in
comparison to all other phobias, complete remissions
are rare;none of the initial AG cases assessed in that
study achieved complete remission.This is true,
despite considerable variations in severity and various
degrees of syndromal shifts that might occur as with
regard to comorbid disorders, in particular the
occurrence of depression. Regarding predictors of
long-term outcome of PD, the presence of severe AG
has been the most consistent finding.[32,66,81,172,173]AG
severity was shown to reduce the chance of full
remission, to increase risk of relapse, and to enhance
chronicity. In the longest follow-up study of PD with
AG treated by exposure (2–14 years), the presence of
residual AG was a strong predictor of relapse into
panic.Additional factors that significantly contri-
bute to chronicity and relapse are comorbid depression,
personality disorders, and high scores on dispositional
measures. It is noteworthy though that there are no
studies that specifically compared PD, PD/AG, and
AG patients in this respect.
A large body of research suggests that
various forms of CBT and antidepressives are highly
effective in treating PD/AG, including long-term
efficacy.There is some controversy whether all
these treatments are equally effective and whether
fits.[175,176]Some meta-analyses suggest that PD/AG
improvements are greater with CBT alone than with
pharamacotherapy alone or combined with psycholo-
gical treatment, yet this conclusion has been criticized
as being flawed.There is an impressive body of
evidence (reviewed by) on the efficacy of exposure in
treating AG. It is difficult, however, to extrapolate from
pre-DSM-III literature whether samples were predo-
minantly associated with panic or not. Similar con-
siderations apply to the efficacy of pharmacological
exposure treatment directed to agoraphobic avoidance
has been used to treat PD with AG. In the London–
Toronto study,homework exposure targeted agor-
was found to be significantly more effective than
alprazolam and a psychological placebo (relaxation)
The clinical course
122Wittchen et al.
Depression and Anxiety
directed to panic. In one study,the mechanisms of
change of PAs during exposure treatment of AG were
specifically investigated. Improvement in AG preceded
amelioration and subsequent disappearance of panic.
Similarly, in the year before relapse of panic, an
increase in agoraphobic avoidance was observed.
In terms of differential treatment effects with regard
to PD, PD/AG, and AG without PA, the results were
inconclusive due to the fact that pharmacological trials
in AG are, to our knowledge, lacking. Within
psychotherapeutic approaches, exposure treatment ap-
pears to be favored in AG over cognitive approaches,
providing some limited evidence for a separation of AG.
The purpose of this review was to examine whether
recent studies provide evidence that AG exists inde-
pendently from PD and history of PAs and, using
classical validators, to review available evidence regard-
ing whether AG is a separate construct. Overall, we
come to the conclusion that AG is a clinically
significant disorder that also exists independently from
PD, and even PA and panic-like features in a substantial
number of cases. We conclude this based on seven main
points. First, considerable epidemiological evidence
from community studies documents consistent and
sizeable rates (of about 50%) of AG without any signs
of PA. These cases do not meet current DSM-IV-TR
criteria of AG without the history of PD. This finding
is incongruent with most, but not all, clinical studies in
the United States that have failed to identify such
patients in significant numbers. Second, consistent
epidemiological, but inconsistent clinical results, fail to
find that AG always occurs secondary to PA or panic-
like symptoms. Third, consistent results document that
AG without panic symptoms is associated with
course with low rates of spontaneous remissions.
Fourth, evidence also suggests differences in patterns
of incidence and gender differentiation between PA,
PD, and AG, as well as differences in response to
treatment. Fifth, additional indirect evidence comes
from the consistent replication of AG as one of the
major dimensions in psychometric and taxometric
investigations of clinical and epidemiological data, as
well as the finding that AG avoidance is an independent
contributor to severity, course, and outcome in PD.
Sixth, some, but not all, evidence suggests differences
in the temporal progression and syndrome stability
between PD, PD/AG, and AG. Finally, it is noteworthy
that those studies that have used specific and explicit
criteria for Agoraphobia—similar or identical to those
used in other phobias, have high interrater and test-
Taken together, these facts and conclusions are
similar to those reached in the DSM-IV Source Book
(Ballenger and Fyer,p 457), namely that in the
majority of cases, AG seems to be associated with
preceding PA or panic-like symptoms and/or are
subsequently mediated by the expectation of panicking
in particular situations. But there is still no empirical
evidence as yet, which unequivocally demonstrates that
AG is temporally primarily and exclusively a function
of PA or panic-like features. However, the fact that
those up to 50% of all agoraphobics fail to report or
remember such primary PA or panic-like experiences
together with the finding that a substantial number of
cases with PA or PD fail to develop AG, lends
considerable support to the notion that AG emerges
for reasons other than or in addition to panic. Thus,
the most plausible interpretation is the existence of
multiple pathogenic pathways involved in AG. The
diagnostic implication is that AG should be defined as a
category in its own right and not merely as a residual to
PD or PAs.
This conclusion is limited by the fact that some
segments of the validation process, namely biologically
based data such as neurobiologic and genetic data, are
not yet available. Further, despite calls for careful
examination of critical issues for a decade (i.e., How
does AG without panic differ from AG with PA or PD?
What are agoraphobics without panic afraid of? What
are panic-like features and are full PA functio-
nally different from subthreshold or limited attacks?),
such studies have not been conducted in a way that
provide definite answers. This might be due to the fact
that past DSM versions no longer provided the
possibility to systematically examine differences bet-
ween PD, PD/AG, and AG without PA or panic-
like features. This is because AG in DSM III-R to
DSM-IV-TR was defined as a residual diagnosis and
most established diagnostic instruments reflected this
fact, thereby precluding the examination of such
THE OPTIONS FOR DSM-V
Before outlining a proposal on how to ultimately
define AG in DSM-V, it might be helpful to review
available options: (1) The first option would be to
delete AG as a diagnosis entirely from the classifica-
tion, but to emphasize AG avoidance as a dimensional
construct by either using a specifier or a separate
criterion with PD. (2) A second option would be to
move AG to Specific Phobia, as a situational subtype.
(3) A third option would be to leave the diagnostic
categories as they are, namely to retain PD without
AG, PD with AG, and AG without the history of PD as
a residual, including the retainment of PA and AG as
syndromes. (4) The fourth option would be the
segregation of PD and AG by specifying more explicit
diagnostic criteria for AG as an independent diagnostic
category in its own right. This would also imply that
123 Review: Agoraphobia Review
Depression and Anxiety
DSM-IVs description chapter and the criteria of AG as
a syndrome could be dropped entirely.
According to this review, as well as the review by
LeBeau et al.there is clearly no empirical evidence
that option 1 (AG specifier) nor option 2 (specific
phobia subtype) are reasonable improvements or
remedies to solve the existent problems (Table 1).
There are no data to support these changes. Further,
they seem to be associated with a range of additional
and far-reaching problems and complications pre-
It is more difficult to decide which of the remaining
options are preferable because some clinical experts and
advisors to the Task Force find the evidence for AG as an
independent diagnosis inconclusive (and thus favor
option 3), while the Task Force members and others
see substantial evidence of the need for making AG an
independent diagnosis. The strongest arguments in favor
of retainment of the current conventions are: (a) The
current conventions work well, (b) AG patients without
PAs and panic-like features are practically not existent in
treatment settings, and (c) concerns about alternative
definitions of AG. The position statements of those
favoring an independent status of AG are: (a) The
residual status of AG as assigned by DSM-IV-TR,
inappropriately and unconditionally implies that one
etiological pathway is emphasized to the exclusion
of others, and this is inconsistent with available data.
(b) The DSM perspective links AG directly to the
primary mechanism of spontaneous PA and their
assumed neurobiological and neuropsychological role
in subsequent AG. Despite unequivocal agreement that
this pathway has been established as one frequent
pathway to AG, substantial evidence points to the
existence of other pathways in a substantial proportion
of cases. (c) The current DSM-IV-TR criteria—unlike
the ICD-10 criteriafor research that are consistent
with an independent conceptualization of AG—have and
will prohibit the collection of data that help to clarify these
alternative pathways and offer empirical guidance for its
resolution. (d) With respect to concerns about the
treatment implications of changing the diagnosis, two
positive consequences are likely. First, the non-assignment
of an AG diagnosis, a disorder for which behavioral
treatments have been established for decades[181–183]might
result in underrecognition and undertreatment as suggested
by extant epidemiological data reviewed above. Further, the
DSM perspective may suggest targeting primarily panic-
relatedsymptoms andassociatedcatastrophic cognitions. In
contrast, individuals with AG who have never had a panic-
like symptom may differ considerably and therapy may
require predominantly targeting agoraphobic avoidance by
THE PROPOSAL FOR DSM-V
Given that this review and the Work Group
discussions have not led to an unanimous consensus
decisions, we propose with the Work Group consensus
a core proposal, supplemented by an alternative
suggestion put forward recently by some of our
advisors and experts. We are further considering
reanalyses of existing clinical data sets and suggest
further exploration and feedback from the field as part
of the DSM-V field trials with regard to our proposal.
We acknowledge at this juncture, however, that the
imperfect nature of current diagnostic assessment
instruments with regard to the core critical issues
might render parts of this exercise difficult and
ultimately unable to provide definite answers. Another
possible strategy might be to take other accounts into
consideration. One would be the consideration that a
revision should not endorse an etiopathogenic pathway
that remains at least partially controversial. Given that
there is substantial disagreement, this would favor a
segregation of PD and AG and the deletion of the
implied hierarchy. Another consideration in favor of
AG as an independent diagnosis might be the
considerable simplification of the DSM structure and
text resulting from our proposal.
DSM-IV-TR DSM-V Proposal
(not a codable disorder)
(not a codable disorder)
Panic Disorder w.o.
Panic Disorder w.
History of Panic Disorder
(not a codable disorder)
A segregation of the two conditions would allow the
lengthy differential diagnostic consideration as well as
the chapter of AG as a syndrome to be dropped
entirely; the two diagnostic variants PD with and
without AG would simply be coded as comorbid
diagnoses. This would further increase clinical utility
by using a dimensional AG specifier on the one hand
and the established PA specifier on the other, and could
be used for those cases where the full diagnostic criteria
were not met. A third consideration would be that the
proposed changes have the advantage that they have
been comprehensively tested in epidemiological re-
search in the past, which revealed high reliability and
validity, and would bring the ICD and DSM systems
In consideration of these issues and because we
cannot foresee any negative effects or clinical implica-
tions, we propose in the following the Task Force’s core
criteria proposal for AG (Table 2). Additionally, we
present in Table 3 the alternative suggested by some
124Wittchen et al.
Depression and Anxiety
TABLE 1. Comparison of Core Agoraphobic Criteria in DSM-III, DSM-III-R, DSM-IV (TR), ICD-9a, and ICD-10
Anxiety disorders (or anxiety and
F40–F48 neurotic, stress-related and
Phobic disorders (or phobic
F40 phobic anxiety disorders
Criteria for Agoraphobia:
A. The individual has a marked fear
of and thus avoids being alone or
in public places from which escape
might be difficult or help not
available in case of sudden
B. There is increasing constriction of
normal activities until the fears or
avoidance behavior dominate the
Criteria for Agoraphobia (Note: not a
A. Anxiety about being in places or
situations from which escape might be
difficult (or embarrassing) or in which
help may not be available in the event
of having an unexpected or
situationally predisposed Panic Attack
or panic-like symptoms. Agoraphobic
fears typically involve characteristic
clusters of situations that 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 automobile
Note: Consider the diagnosis of
Specific Phobia if the avoidance is
limited to one or only a few specific
situations, or Social Phobia if the
avoidance is limited to social
B. The situations are avoided (e.g., travel
is restricted) or else are endured with
marked distress or with anxiety about
having a Panic Attack or panic-like
symptoms, or require the presence of a
C. The anxiety or phobic avoidance is not
better accounted for by another mentaldisorder, such as Social Phobia (e.g.,
avoidance limited to social situations
because of fear of embarrassment),
Specific Phobia (e.g., avoidance limited
to a single situation like elevators),
Obsessive–Compulsive Disorder (e.g.,
avoidance of dirt in someone with an
obsession about contamination),
Posttraumatic Stress Disorder (e.g.,
avoidance of stimuli associated with a
severe stressor), or Separation Anxiety
A. Marked and consistently manifest
fear in or avoidance of at least two of
the following situations: (1) crowds;
(2) public places; (3) traveling alone;(4) traveling away from home
B. Symptoms of anxiety in the feared
situation at some time since the
onset of the disorder, with at least
two symptoms present together, on
at least one occasion, from the list
below, one of which must have been
from items (1) to (4): Autonomic
arousal symptoms (1–4), Symptomsconcerning chest and abdomen
(5–8), Symptoms concerning brain
and mind (9–12), General
The presence or absence of panic
disorder (F41.0) on a majority ofoccasions when in the
agoraphobic situation may be
specified by using a fifth
125 Review: Agoraphobia Review
Depression and Anxiety
TABLE 1. Continued
Disorder (e.g., avoidance of leaving
home or relatives)
300.22 Agoraphobia without panic
[DSM text portion: Where there is
no history of Panic Attacks (or
this information is lacking), the
diagnosis of Agoraphobia without
Panic Attacks should be made]
300.22 Agoraphobia without history
of Panic Disorder
A. 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 suddenly developing a
symptom(s) that could be
incapacitating or extremely
embarrassing. Examples include:
dizziness or falling, depersonalizaton or derealization, loss of bladder or bowel control, vomiting, or
cardiac distress. 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
B. Has never met the criteria for
Panic Disorder. Note: Includes
specifier for limited symptom attacks
(with or without)
300.22 Agoraphobia without history of
A. The presence of Agoraphobia related
to fear of developing panic-like
symptoms (e.g., dizziness or
B. Criteria have never been met for
F40.00 Agoraphobia without Panic
Note: Severity in F40.00 may be rated by
indicating the degree of avoidance,
taking into account the specific cultural
setting. Severity in F40.01 may be rated
by counting the number of panic attacks
300.21 Agoraphobia with Panic
[DSM text portion: Often the initial
phase of the disorder consists of
recurrent panic attacks. The
individual develops anticipatory
fear of having such an attack and
becomes reluctant or refuses to
enter a variety of situations that
are associated with these attacks.
When there is a history of panic
attacks associated with avoidance
behavior, the diagnosis of
Agoraphobia with Panic Attacks
should be made.]
300.21 Panic Disorder with
Agoraphobia A. Meets the criteria for Panic
B. Agoraphobia: Fear of being in
places or situations from which
escape might be difficult (orembarrassing) or in which help
might not be available in the event
of a panic attack. (Include cases in
which persistent avoidance
behavior originated during and
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
300.21 Panic Disorder with
AgoraphobiaA. Both criteria for Panic Disorder met
(not listed here)
B. The presence of Agoraphobia
F40.01 Agoraphobia with Panic
Note: Severity in F40.01 may be rated by
counting the number of panic attacks
126 Wittchen et al.
Depression and Anxiety
either restricts travel or needs a
companion when away from
home, or else endures
agoraphobic situations despite
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
severity specifiers for agoraphobic
avoidance (mild, moderate, severe)
course specifier for agoraphobic
avoidance (in partial remission, in
severity specifier for panic attacks
(mild, moderate, severe)
course specifier for panic attacks (in
partial remission, in full remission)
Anxiety states (or anxiety neurosis)
F41 other anxiety disorders
300.01 Panic disorder
D. The disorder is not associated
300.01 Panic disorder without
A. Meets the criteria for Panic
B. Absence of Agoraphobia, as
severity specifier for panic attacks
(mild, moderate, severe)
course specifier for panic attacks (in
partial remission, in full remission)
300.01 Panic disorder without
A. Both criteria for Panic Disorder met
(not listed here)
B. Absence of Agoraphobia
Note: Does not include any specifiers
F41.0 Panic disorder [episodic
Note: The range of individual variation of
both content and severity is so great that
two grades, moderate and severe, may be
specified, if desired, with a fifth
F41.00 Panic disorder—moderate: at least
four panic attacks in a four-week period.
F41.01 Panic disorder—severe: at least four
panic attacks per week over a four-week period
Agoraphobia has primary consideration
over Panic Disorder
Agoraphobia is considered secondary to
Agoraphobia is considered secondary to Panic
Attacks; Panic Disorder has primary
consideration over Agoraphobia
Agoraphobia has primary consideration over
Agoraphobia—unlike social or simple
phobia—has no specific diagnostic
criteria anymore (exposure provoked
anxiety reaction, avoidance,
recognition, distress, and impairment
has been merged into one big
Agoraphobia—unlike social or simple
phobia—has no specific diagnostic criteria
anymore (exposure provoked anxiety
reaction, avoidance, recognition, distress,
and impairment has been merged into
one big criterion)
aICD-9: 300.2 Phobic disorders: 300.22 Agoraphobia without Panic Attacks, 300.21 Agoraphobia with Panic Disorder; 300.0 Anxiety States: 300.01 Panic Disorder without Agoraphobia (Note:
Agoraphobia has primary consideration over Panic Disorder).
127 Review: Agoraphobia Review
Depression and Anxiety
advisors that agree on making agoraphobia a separate
codable disorder, but suggest slightly different criteria
to stimulate discussion. The Task Forces core proposal
would considerably simplify the current DSM classifi-
cation by allowing the clinician to diagnose only AG (in
the absence of PD criteria or if PD criteria are only
partially met), PD and AG (if criteria are fully met for
both), or only PD. Because degree of agoraphobic
avoidance in PD is an important marker in PD
(severity, prognosis, treatment) and the fact that the
proposed AG criteria have a high threshold, one should
further consider a dimensional specifier for PD
whenever full AG criteria are not met. This would be
similar to the specifier for presence of PA in AG as well
as in other disorders, as currently recommended for
consideration for DSM-V.The proposal further uses
the same criteria as for other phobic disorders—thus
increasing consistency—and specifies the syndrome by
multiple criteria that are, by and large, identical to
those used for specific and social phobia.
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2. Craske MG, Kircanski K, Epstein A, et al. Panic disorder
literature review. Depress Anxiety, in this issue.
TABLE 2. DSM-V Task Force Core Proposal for Agoraphobia
A. Marked fear or anxiety about more than one situation from a characteristic cluster of agoraphobic situations. Agoraphobic situations typically
include: being outside the home alone; public transportation (e.g., traveling in a bus, train, ship, plane); open spaces (e.g., parking lots and
market place); being in shops, the theater, or cinemas; standing in line or being in a crowd
B. The individual fears and/or avoids these situations because escape might be difficult or help might not be available in the event of incapacitation
or panic-like symptoms
C. The agoraphobic situations almost invariably provoke immediate fear or anxiety
D. The agoraphobic situations are avoided, require the presence of a companion, or are endured with intense fear or anxiety
E. The fear or anxiety is out of proportion to the actual danger posed by the agoraphobic situations
F. The duration is at least 6 monthsa
G. The fear, anxiety, and avoidance cause clinically significant distress or impairment in social, occupational, or other important areas of
H. The fear, anxiety, and avoidance are not restricted to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a
general medical condition (e.g., cardiopulmonary disorders)b
I. The fear, anxiety, and avoidance are not restricted to the symptoms of another mental disorder, such as Specific Phobia (e.g., if limited to one or
a few circumscribed phobic objects or situations), Social Phobia (e.g., in response to feared social situations), Obsessive–Compulsive Disorder
(e.g., in response to dirt in someone with an obsession about contamination), Posttraumatic Stress Disorder (e.g., in response to stimuli
associated with a traumatic event), or Separation Anxiety Disorder (e.g., in response to being away from home or close relatives)c
Note: Agoraphobia is a codable disorder.
aThe construct duration was added to reduce reliane on impairment and distress. A 6-month duration is considered for all phobias, awaiting
secondary data analyses and field testing.
bThe criterion is retained provisionally, although no empirical evidence for physiologic mechanism relating to agoraphobia is available.
cThe differential diagnostic considerations proposition suggest provisionally the word ‘‘not restricted to’’ instead of ‘‘not better accounted for’’
awaiting more general decisions of the DSM-V committee.
TABLE 3. Alternative Option Proposed (without accompanying Literature Review)
A. Anxiety about being, or anticipating being, in places or situations from which escape might be difficult or embarrassing, or in which help may
not be available, in the event of having a panic attack, being suddenly incapacitated, or having sudden physical symptoms (including panic-like
symptoms or other somatic events such as dizziness, vomiting, or diarrhea)
Agoraphobic fears typically involve characteristic clusters of situations that include being outside the home alone; being in a crowd or standing
in a line; being in the center of a theater row or on a bridge; traveling in a bus, train, automobile, or plane; or being in open spaces (e.g., parking
lots and market place)
B. Situations from which escape might be difficult are avoided (e.g., travel is restricted); endured with marked distress or with anxiety about having
a Panic Attack, panic-like, or other symptoms; or require the presence of a companion
C. The fear, anxiety, or avoidance cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
D. The anxiety or phobic avoidance is not restricted to the symptoms of another mental disorder, such as Social Phobia (e.g., avoidance limited to
social situations because of fear of embarrassment), Specific Phobia (e.g., avoidance limited to one or only a few specific situations like dogs or
elevators), Social Phobia (e.g., avoidance limited to social situations), Obsessive–Compulsive Disorder (e.g., avoidance of dirt in someone with
an obsession about contamination), Posttraumatic Stress Disorder (e.g., avoidance in response to stimuli associated with a traumatic event), or
Separation Anxiety Disorder (e.g., avoidance of leaving home or relatives)
Note: Agoraphobia is a codable disorder.
128 Wittchen et al.
Depression and Anxiety
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