Clinical Review & Education

The Rational Clinical Examination

Does This Patient Have Generalized Anxiety

or Panic Disorder?
The Rational Clinical Examination Systematic Review
Nathaniel R. Herr, PhD: John W. Williams Jr, MD, MHSc; Sophiya Benjamin, MD; Jennifer McDuffie, PhD

[J Supplemental content at
IMPORTANCE In prim ary care settings, generalized anxiety disorder (GAD) and panic disorder jama.com

are com m on b u t underrecognized illnesses. Identifying accurate and feasible screening H CMEQuizat
instrum ents fo r GAD and panic disorder has the potential to im prove detection and facilitate jamanetworkcme.com and
treatm ent. CME Questions page 89

OBJECTIVE To systematically review the accuracy o f self-report screening instrum ents in

diagnosing GAD and panic disorder in adults.

DATA SOURCES We searched MEDLINE, PsycINFO, and th e Cochrane Library fo r relevant

articles published from 1980 through April 2014.

STUDY s e l e c t io n Prospective studies o f diagnostic accuracy th a t compared a self-report

screening instrum ent fo r GAD o r panic disorder w ith th e diagnosis made by a trained clinician
using Diagnostic and Statistical Manual o f Mental Disorders or International Classification of
Diseases criteria.
Author Affiliations: Department of
Psychology, American University,
RESULTS We screened 3 6 0 5 titles, excluded 3529, and perform ed a more detailed review o f Washington, DC (Herr); Durham
76 articles. We identified 9 screening instrum ents based on 13 articles from 10 unique studies Veterans Affairs Evidence-based
Synthesis Program (ESP) Center,
fo r the detection o f GAD and panic disorder in prim ary care patients Across all studies,
Durham, North Carolina (Williams,
diagnostic interview s determ ined th a t 257 o f 2785 patients assessed had a diagnosis o f GAD McDuffie): Duke University
w hile 224 o f 2637 patients assessed had a diagnosis o f panic disorder. The best-perform ing Department of Medicine, Durham.
test fo r GAD was the Generalized A nxiety Disorder Scale 7 Item (GAD-7), w ith a positive North Carolina (Williams, McDuffie);
Grand River Hospital, Kitchener,
likelihood ratio o f 5.1 (95% Cl, 4.3-6.0) and a negative likelihood ratio o f 0.13 (95% Cl,
Ontario, Canada (Benjamin);
0.07-0.25). The best-perform ing test fo r panic disorder was the Patient Health Department of Psychiatry and
Questionnaire, w ith a positive likelihood ratio o f 78 (95% Cl, 29-210) and a negative Behavioral Neurosciences, McMaster
likelihood ratio o f 0 .2 0 (95% Cl, 0.11-0.37). University, Hamilton, Ontario, Canada
(Benjamin).
Corresponding Author: John W.
c o n c l u s io n s AND relevance Two screening instrum ents, th e GAD-7 fo r GAD and the
Williams Jr, MD, MHSc, 411W Chapel
Patient Health Questionnaire fo r panic disorder, have good performance characteristics and Hill St, Ste500, Durham, NC 27701
are feasible fo r use in prim ary care. However, fu rth e r validation o f these instrum ents is (jw.williams@duke.edu).
needed because neither instrum ent was replicated in more than 1 prim ary care population. Section Editors: David L. Simel, MD,
MHS, Durham Veterans Affairs
Medical Center and Duke University
JAMA. 2014;312(1):78-84. doi:10.1001/jama.2014.5950
Medical Center, Durham, NC; Edward
H. Livingston, MD, Deputy Editor.

to determ ine w h e th er Ms B's sym ptom s and related behaviors in­

Clinical Scenario dicate an anxiety disorder?

Ms B is a 42-year-old com puter program m er w ith a history o f irri­

table bowel syndrom e w ho presents to her prim ary care physician
fo r a blood pressure check. Six m onths ago, she began caring fo r her
chronically ill mother, and she reports increased stress. You note that
she had a visit to urgent care after having transient chest pain, short­
ness o f breath, and palpitations. Myocardial ischemia was ruled o u t
w ith o u t req u irin g hospital adm ission. Female sex, stressful life
events, and chronic medical illness place her at increased risk fo r an
anxiety disorder. W hat tools could be used by th e physician or nurse
Why Is This Question Important?
A nxiety disorders are prevalent, are o fte n chronic, cause im p o r­
ta n t functional im pairm ent, and are associated w ith increased health
care use.1,2 Two o f the m ore com m on anxiety disorders are gener­
alized anxiety disorder (GAD) and panic disorder. In co m m u n ity
samples, the estim ated lifetim e prevalence rates fo r GAD and panic
disorder are 5.1% and 3.5%, respectively, and 12-month rates (ex-

78 JAMA July 2,2014 Volume 312, Number 1 jama.com

Screening fo r Generalized Anxiety or Panic Disorder The Rational Clinical Examination Clinical Review & Education

Table 1. D ia g n ostic C riteria fo r Generalized A n x ie ty and Panic D iso rd er3

Main Symptoms Associated Symptoms Functional Qualifier Exclusions

GAD (DSM-5)

Excessive worry and d ifficu lty controlling worry Individuals with GAD often experience Significant Not due to another Axis 1illness,
for at least 6 mo Trembling/shakiness impairment in medical illness, or substance
>3 of the follow ing symptoms: Muscle aches functioning (drug of abuse or medication)
Restlessness Sweating/nausea/diarrhea
Easily fatigued Irritable bowel
Irritability Headaches
D ifficulty concentrating
Muscle tension
Sleep disturbance
Panic Disorder (DSM-5)

Recurrent and unexpected panic attacks Panic attacks are an abrupt surge in Significant Not due to another Axis 1illness,
At least 1 mo of >1 of the follow ing symptoms: symptoms, including impairment in medical illness, or substance
Persistent concern about having another attack Palpitations functioning (drug of abuse or medication)
Significant maladaptive change in behavior Sweating
related to attacks Trembling/shaking
Shortness of breath/choking
Chest pain
Nausea
Dizziness
Chills/heat sensations
Paresthesias
Derealization
Fear of losing control
Fear of dying

Abbreviations: DSM, Diagnostic and Statistical Manual o f Mental Disorders; GAD, exception: the DSM-5 no longer asks diagnosticians to determine whether
generalized anxiety disorder. panic disorder is w ith or w itho u t agoraphobia.
3 The DSM-5 criteria fo r these disorders are identical to those o f DSM-IV, w ith 1

perienced anytim e w ithin the last 12 months, including currently) are
3.1% and 2.3%, respectively.3 Primary care patients have higher rates
o f both GAD (8% ) and panic disorder (6.8% ), and th e prevalence
rate o f GAD increases to 22% among those w ith anxiety problem s
as th e presenting concern.4,5 Many patients w ith anxiety disorders
present to th e ir prim ary care physician w ith som atic sym ptom s,
which contributes to underrecognition o f these conditions and can
result in unnecessary and costly diagnostic te stin g.6 When diag­
nosed, both GAD and panic disorder can be treated successfully w ith
m ed ica tio n a n d /o r psychotherapy. Furtherm ore, care m anage­
m ent trials have shown th a t screening, coupled w ith effective p ri­
mary care trea tm e nt, improves outcom es fo r patients w ith anxiety
disorders.7
How to Diagnose GAD and Panic Disorder
A nxiety sym ptom s such as w o rry o r physical tension are exp e ri­
enced nearly universally in response to stressful or threatening situ­
ations. Anxiety may bean adaptive em otional experience th a t helps
a person to avoid or prepare fo r fu tu re challenges. In contrast, anxi­
ety disorders cause severe and persistent symptoms that impair func­
tioning. The criterion standards fo r GAD and panic disorder are sum ­
marized in Table 1. Generalized anxiety disorder is characterized by
at least 6 m onths o f persistent, excessive anxiety or w o rry th a t is
d ifficu lt to control and causes significant distress or im pairm ent. The
diagnosis requires at least 3 o f 6 additional sym ptom s: restless­
ness, fatigue, irritability, decreased concentration, muscle tension,
and sleep d istu rb a n ce .8 Panic d iso rd e r is characterized by fr e ­
quent and unexpected panic attacks, and individuals w ith this dis­
order exhibit intense w orry about having them. Panic attacks are pe­
riods o f intense fear or te rro r associated w ith autonom ic arousal, and
typical sym ptom s include palpitations; sweating; tre m b lin g o r shak­
ing; shortness o f breath; feeling o f choking; chest pain or discom ­
fo rt; nausea or abdom inal distress; feeling dizzy, unsteady, lig h t­
headed, o r fa in t; paresthesias; chills; o r h o t flushes.8 A lth o u g h
agoraphobia was previously considered to be a subtype w ith in the
panic disorder diagnosis, in th e Diagnostic and Statistical Manual o f
Mental Disorders (Fifth Edition) (DSM-5) it is now classified as a dis­
crete disorder characterized by avoidance o f public spaces fo r fear
o f having a panic attack.
A clinical evaluation o f anxiety disorders can begin w ith an open-
ended question such as "Tell me about your worries, fears, con­
cerns, and stresses, and how th e y affe ct you."9 W hen GAD is in ­
quired about specifically, a question such as "Would you say th a t you
have been bothered by 'nerves' or feeling anxious or on edge?" can
elicit sym ptom s o f th e disorder. When inquiring about panic disor­
der specifically, th e clinician can ask a question such as "Did you ever
have a spell or an attack when all o f a sudden you fe lt frightened,
anxious, or very uneasy?"10
Another approach to th e diagnosis o f GAD and panic disorder
in prim ary care clinics is to ask all patients, or those w ith risk fac­
tors, to com plete a self-report screening instrum ent. Depending on
the prevalence o f th e disease, the physician may w ant to optim ize
the positive likelihood ratio (LR+) to avoid unnecessary additional
testing or the negative likelihood ratio (LR-) to be confident that anxi­
e ty disorders do n o t require additional consideration. An alterna­
tive as part o f the initial diagnostic assessment would be to evalu­
ate only patients w ho present w ith sym ptom s th a t raise suspicion
o f an anxiety disorder. For routine use in prim ary care settings, the
ideal instrum ent should be brief, accurate, easy to score and in te r­
pret, and studied in mixed populations o f patients. For patients w ith
a positive screening result, a careful clinical interview coupled w ith
a targeted physical examination and any indicated diagnostic te s t­
ing to evaluate fo r an underlying explanatory medical illness is re­
quired fo r a de finitive diagnosis. To inform decision m aking regard-

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 Clinical Review & Education The Rational Clinical Examination
ing a standard instrum ent to assess prim ary care patients fo r anxiety
disorders, w e conducted a system atic review o f th e literature to
evaluate th e perform ance o f self-report instrum ents used to diag­
nose GAD and panic disorder in prim ary care settings.
Methods
Search S tra te g y a n d S tu d y S e le ctio n
We searched MEDLINE, PsycINFO, and th e Cochrane Library from
January 1980 through April 2014 fo r studies conducted in general
medical settings th a t compared a self-report instrum ent w ith an ac­
ceptable criterion standard. The search strategy included the term s
generalized anxiety disorder and panic disorder, th e names o f
a n xie ty instrum ents, and a validated search filte r fo r retrie vin g
articles on th e diagnosis o f health disorders (eA ppendix 1 in the
Supplem ent).11,12 Electronic searches were supplem ented by exam­
ining the bibliographies o f systematic reviews, a recent technical re­
port, and the studies we ultim ately included in the technical report.13
We included studies th a t were conducted w ith patients aged
at least 18 years w ho were treated in general medical settings (ie,
general internal medicine, fam ily medicine, geriatrics, emergency
d e p a rtm e n t, and w om en's health clinic); com pared s e lf-re p o rt
questionnaires fo r GAD o r panic d iso rd e r w ith diagnostic in te r­
view s, using c rite ria fro m e ith e r th e Diagnostic and Statistical
Manual of Mental Disorders (Third Edition) ( DSM-III) o r Interna­
tional Classification o f Diseases, Ninth Revision, o r m ore recent
editions o f these publications; and were peer-reviewed, English-
language publications from North America, western Europe, New
Zealand, o r Australia. Geographic and language lim ita tio ns were
designed to id e n tify studies w ith th e highest a p p lica b ility to US
p o p u la tio n s . T w o re v ie w e rs in d e p e n d e n tly e x a m in e d each
abstract fo r relevance. Next, fu ll-te x t articles id e ntified by either
review er as p o te n tia lly relevant w ere exam ined by 2 reviewers,
w ho evaluated the articles' e ligibility according to predeterm ined
criteria (eA ppendix 2 in th e Supplem ent). Disagreem ents were
resolved by discussion or a th ird reviewer.
Data A b s tra c tio n a nd Q u a lity R atings
We extracted selected data elements inform ed by the principles o u t­
lined by the Standards fo r Reporting o f Diagnostic Accuracy.14These
elements included descriptors to assess applicability (eg, setting,
sample characteristics, anxiety disorder prevalence), test p e rfo r­
mance, and q u ality (eg, recru itm en t m ethod, blinding, reference
standard, sample size) o f each study. When provided, raw data for
the 2 x 2 table were extracted, and when n o t provided, data were
derived from oth er perform ance characteristics such as sensitivity
and specificity. When results w ere adjusted fo r th e sampling de­
sign (eg, partial verification o f the criterion-based diagnosis), we use
th e adjusted results. A second review er verified all data abstrac­
tions, and disagreements were resolved by review er discussion or
by obtaining a th ird reviewer's opinion.
For each selected study, raters com pleted th e Q uality Assess­
m ent o f Diagnostic Accuracy Studies, a 14-item to o l th a t assesses
study quality (eAppendixes 3-4 in the Supplement). We followed rec­
om m endations from The Rational Clinical Examination series15 by
assigninga level o f evidence for each study, rangingfrom I (high qual­
ity) to V (low quality).
80 JAM A July 2,2014 Volume 312, Number 1
Screening for Generalized Anxiety or Panic Disorder
S ta tis tic a l M e th o d s
Sensitivity, specificity, and likelihood ratios (LRs) were calculated w ith
CIs fo r instrum ents evaluated in each study. An LR+ is the ratio o f
th e likelihood o f a positive test result in an individual w ith th e con­
d itio n to th e likelihood o f a positive te st result in an individual w ith ­
o u t it. An LR- is th e ratio o f th e likelihood o f a negative te st result in
an individual w ith th e condition to th e likelihood o f a negative test
result in an individual w ith o u t it. Tests w ith higher specificity gen­
erally have higher LRs, and positive results are m ost useful fo r iden­
tify in g patients w ith an anxiety disorder, whereas tests w ith higher
sensitivity generally have lower LRs, and negative results are most
useful fo r ruling o u t patients w h o do n o t have an anxiety disorder.
If an LR+ is 2, a positive test result (in this case, a positive score on
an anxiety questionnaire) is tw ice as likely to occur in an individual
w ith an anxiety disorder as opposed to an individual w ith o u t one.
An LR- o f 0.2 means th a t a negative screening result is o n e -fifth as
likely to occur in an individual w ith an anxiety disorder as opposed
to an individual w ith o u t one. Because GAD and panic disorder are 2
d istin ct clinical entities, w e calculated sum m ary estim ates sepa­
rately fo r studies on GAD-specific instrum ents and panic disorder-
specific instrum ents.
To estimate th e prior probability o f GAD and panic disorder, we
calculated a random -effects summ ary measure from th e included
studies. The Sym ptom Driven Diagnostic System fo r Primary Care
(SDDS-PC) instrum ent was evaluated in 3 studies, which allowed us
to calculate separate sum m ary measures fo r the sensitivity, speci­
ficity, and LR w ith 95% CL All o th er instrum ents were evaluated in
only 1 study, fo r which we show th e test's p o in t estim ate and 95%
CL We explored heterogeneity among the studies w ith Cochran Q
and I2, which describe the percentage o f to ta l variation across stu d ­
ies due to heterogeneity rather than chance, and we used m eta ­
regression to evaluate the effe ct o f age and sex on th e LRs. Fletero-
geneity was categorized as low, m oderate, o r high according to I2
values o f 25%, 50% , and 75%, respectively. We used Com prehen­
sive Meta-Analysis (Biostat version 2.2 .06 4 ) fo r all meta-analyses.
Results
S tu d y C h a ra cte ristics
We id entified 3 6 0 5 unique citations fro m a com bined electronic
search ofMEDLINE via PubM ed(n = 1167), PsycINFO (n = 1810),and
the Cochrane Library (n = 6 0 5 ) and from a manual examination o f
references (n = 23). A fte r inclusion and exclusion criteria were ap­
plied, 3529 articles were excluded at th e title and abstract level. We
retrieved 76 articles fo r fu ll-te x t review and excluded 63. For data
abstraction and evidence synthesis, w e retained a to ta l o f 13 ar­
ticles representing 10 unique studies.16'25 Because some studies in ­
cluded more than 1sample or evaluated more than 1 instrum ent, we
included 14 unique evaluations o f anxiety instrum ents. The eFigure
in th e Supplem ent illustrates the literature search process.
O f 13 articles describing 10 studies, 9 d ifferent instrum ents were
evaluated (Table 2). Across all studies, diagnostic interview s d e ter­
m ined th a t 257 o f 2785 patients assessed had a diagnosis o f GAD
w hile 224 o f 2637 patients assessed had a diagnosis o f panic disor­
der. The average age o f patients in studies o f GAD (n = 6) (Table 3)
was sim ilar across 5 o f th e samples18,21,23,25 (range, 38-47 years),
whereas 1 study20 contained older patients (mean age, 73 years).
jama.com
Screening fo r Generalized Anxiety or Panic Disorder The Rational Clinical Examination Clinical Review & Education

Table 2. Characteristics of 8 Self-report Measures for Generalized Anxiety and Panic Disorder

No. of Time Score Usual Cut Literacy Tracking of

Instrument Items Response Format Frame Range Point Levels3 Completion Time Symptoms
GAD

ADS-GA26 11 Yes or no Unknown 0-11 4-5 Easy Unknown Unknown

GAD-723 7 4 Frequency ratings: 2 wk 0-21 5 = mild Average Unknown Unknown

not at all, several days, 10 = moderate
more than half the days, 15 = severe
nearly every day
GAD-Q-IV25 9 5 Yes or no; 2 Likert 6 mo 0-12 >5.7 Average Unknown Unknown
(9 response choices);
1 count of worries;
1 physical symptom
checklist
SDDS-PC18 4 GAD Yes or no 6 mo 0-5 Unclear Easy <2 min Yes (scale has
separate
longitudinal
tracking module)
Panic Disorder

BPDS27 4 Symptom severity: very None 0-16 >11 Average Unknown Unknown
little , a little , some,
much, very much
PHQ22 (panic module 5 Yes or no 4wk 0-5 Yes on all 5 Easy <1 min fo r 42% No
from 3-page questions 1-2 min for 43%
diagnostic fo rm )b 3-5 min for 13%
>5 min fo r 3%
SDDS-PC18 5 Panic Yes or no Past mo 0-5 Unclear Easy <2 min

Unnamed 10-item 10 Symptom severity: not at all, Unknown 0-50 >21 Average Unknown Unknown
scale16 a little bit, moderately,
quite a bit, a great deal
GAD or Panic Disorder

BAI-PC17 7 4 Items of symptom severity Past 2 wk 0-21 >5 Easy =1 min Unknown
(GAD and panic) to today
PRIME-MD24(Multiple 3 Yes or no Past mo 0-3 >1 Easy <1 min No
components with
GAD and panic)

Abbreviations: ADS-GA, Anxiety Disorder Scale-Generalized Anxiety: BAI-PC,
Beck Anxiety Inventory-Primary Care: BPDS, Brief Panic Disorder Screen:
GAD-Q-IV, Generalized Anxiety Disorder Questionnaire Fourth Edition: GAD-7,
Generalized Anxiety Disorder Scale 7 Items; PHQ, Patient Health Questionnaire;
PRIME-MD, Primary Care Evaluation o f Mental Disorders; SDDS-PC, Symptom
Driven Diagnostic System for Primary Care.
3 Easy indicates third- to fifth-grade reading level; average, sixth- to ninth-grade
reading level.
bThe PHQ has been revised such that the fifth question in the panic module has
11 subitems; current scoring requires a yes response to the firs t 4 questions
and yes to £ 4 o f 11 subitems for question 5.

The studies were similar in sex, w ith 64% to 85% wom en. The stud­
ies o f panic disorder (n = 6)(T able3)am ongunselected patients in­
cluded participants w ith a m ore homogeneous age (mean range,
39-54 years), w ith a similar d istribu tio n o f wom en (66% -72% ). A
study o f patients presenting w ith palpitations included similarly aged
participants (mean age, 47 years), w ith a slightly smaller p ro p o r­
tio n o f wom en (57% ).16
M ost studies were rated low risk o f bias (Table 3, eAppendixes
3-4). All o f th e questionnaires were self-adm inistered and did not
require specialized equipm ent or trained personnel, making them
suitable fo r patients to com plete in a variety o f settings. Based on
diagnostic interviews, th e random -effects sum m ary estim ate for
prevalence o f GAD was 10.1% (95% Cl, 5.7%-17%), whereas preva­
lence o f panic disorder was 8.8% (95% Cl, 6.6%-12%). The panic dis­
order range does not include the results o f Barsky et al,16which found
a panic disorder prevalence o f 26% among patients presenting w ith
a com plaint o f heart palpitations.
Performance Characteristics of Self-report
Screening Instruments
Generalized Anxiety Disorder
The Generalized A nxiety Disorder Scale 7 Item (GAD-7), using a cut
p o in t o f greate rth a n or equal to 10, had good sensitivity (89% ) and
specificity (83% ), had th e highest LR+ (5.1; 95% Cl, 4.3-6.0), and is
also th e only measure th a t reported te st-re te st re lia b ility (in tra ­
class co rrelation,0.83). AGAD-7score less than 10 had an L R -(0.13;
95% Cl, 0.07-0.26) similar to th a t o f th e Generalized A nxiety Dis­
order Questionnaire Fourth Edition at a threshold less than 5.7 (LR-,
0.18; 95% Cl, 0.0 6-0 .5 2 ; P = .65 fo r the comparison). The SDDS-PC
takes less than 2 m inutes fo r com pletion and has an "easy" literacy
level w ith 3 d iffe re n t form ulations evaluated in d iffe rin g popula­
tions (sum m ary LR+, 2.6 [95% Cl, 1.6-4.1]; LR-, 0.31 [95% Cl, 0.22-
0.43]). The A nxiety Disorder Scale-Generalized Anxiety was stu d ­
ied in older patients (mean age 72 years) and had th e least useful
LR-, 0.70 (95% Cl, 0.45-1.1).
The instrum ents18,20'21'23,25 showed high heterogeneity (LR+:
/2 = 93% , P < .001; LR-: I2 = 76% , P = .001) am ong studies con­
ducted in prim ary care w ith unselected patients. Although m eta­
regression revealed th a t the LR+ did not vary by the mean age in the
study samples (P = .23), older mean age was strongly associated w ith
th e LR-, accounting fo r 94% o f th e heterogeneity (P < .001). Stud­
ies o f GAD w ith a higher frequency o f younger patients found a lower
LR- (easier to rule o u t GAD) compared w ith studies w ith older pa­
tients. Sex accounted fo r only 29% o f th e heterogeneity in th e sum ­
mary LR+ (P < .22) and only 5% o f th e heterogeneity in th e sum ­
m ary LR- (P = .43). Thus, these screening in strum ents fo r GAD

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 Clinical Review & Education The Rational Clinical Examination Screening fo r Generalized Anxiety or Panic Disorder

Table 3. P e rfo rm an ce C haracteristics o f S e lf-re p o rt In stru m e n ts

(95% Cl)
No. (% Age, Mean Quality
Instrument Study Prevalence)4 (SD), y Females, % Sensitivity Specificity LR+ LR- Rating
GAD

GAD-7 Spitzer et al,23 2 0 06 965 (7.6) 47 (16) 65 0.89 0.83 5.1 0.13 1
(0.82-0.96) (0.80-0.85) (4.3-6.0) (0.07-0.26)
GAD-Q-IV Moore et al,25 2014 99 (27) 3 9 (1 3 ) 85 0.89 0.63 2.4 0.18 III
(0.77-1.0) (0.51-0.74) (1.7-3.3) (0.1-0.5)
ADS-GA Krasucki et al,20 1999 88 (15) 73 64 0.39 0.88 3.2 0.70 III
(0.12-0.65) (0.81-0.95) (1.3-8.0) (0.45-1.08)
SDDS-PC L e o n e ta l,2 1 1996 5 0 1 (1 6 ) 49 (13) 66 0.74 0.82 4.1 0.32 1
(0.64-0.83) (0.78-0.86) (3.2-5.2) (0.22-0.46)
Broadhead et a l,18 257 (5.4) 40 (13) 79 0.92 0.54 2.0 0.15 1
1995 (0.76-1.00) (0.49-0.59) (1.6-2.4) (0.02-1.01)
Broadhead et al,18 388 (3.1) 3 9 (1 2 ) 73 0.86 0.60 2.1 0.24 1
1995 (0.67-1.00) (0.53-0.66) (1.6-2.8) (0.07-0.87)
Summary SDDS-PC 0.78 0.67 2.6 0.31
(0.66-0.87) (0.47-0.82) (1.6-4.1) (0.22-0.43)
Panic Disorder

PHQ Spitzer e ta l,22 1999 585 (6.0) 46 (17) 66 0.81 0.99 78 0.20 1
(0.68-0.93) (0.98-1.00) (29-210) (0.11-0.37)
SDDS-PC L eo n e ta l,2 1 1996 501 (8.0) 4 9 (1 3 ) 66 0.70 0.91 7.9 0.33
(0.56-0.84) (0.88-0.93) (5.5-11) (0.20-0.53)
Broadhead e ta l,18 257 (6.2) 40 (13) 79 0.78 0.80 3.9 0.28 1
1995 (0.62-0.94) (0.76-0.84) (2.9-5.2) (0.14-0.56)
Broadhead e ta l,18 388 (7.0) 39 (12) 73 0.63 0.83 3.8 0.45 1
1995 (0.39-0.86) (0 .7 8 -0 .8 8 ) (2.3-6.0) (0.23-0.70)
Summary SDDS-PC 0.71 0.86 4.9 0.35
(0.60-0.80) (0.77-0.91) (3.0-7.9) (0.25-0.48)
10-Item scale Barsky e ta l,16 1997 124 (26) 47 57 0.72 0.71 2.4 0.40 II
(0.56-0.88) (0.60-0.80) (1.7-3.6) (0.22-0.70)
BPDS Johnson e ta l,19 2007 295 (14) 5 4 (1 1 ) 66 0.61 0.29 0.86 1.36 1
(0.46-0.76) (0.23-0.35) (0.66-1.1) (0.88-2.08)
GAD or Panic Disorder

BAI-PC Beck e ta l,171997 56 (23) 49 (16) 73 0.85 0.81 4.6 0.19 III
(0.65-1.00) (0.67-0.92) (2.3-8.9) (0.05-0.68)
PRIME-MD Spitzer et al,24 1994 431 (18) 55 (16) 60 0.93 0.53 2.0 0.12 1
(0.88-0.99) (0.48-0.58) (1.8-2.3) (0.05-0.29)

Abbreviations: ADS-GA, Anxiety Disorder Scale-Generalized Anxiety; BAI-PC,
Beck Anxiety Inventory-Primary Care; BPDS, Brief Panic Disorder Screen; GAD,
generalized anxiety disorder; GAD-Q-IV, Generalized Anxiety Disorder
Questionnaire Fourth Edition; GAD-7, Generalized Anxiety Disorder Scale 7 Item;
LR, likelihood ratio; PHQ, Patient Health Questionnaire; PRIME-MD. Primary
Care Evaluation o f Mental Disorders; SDDS-PC, Symptom Driven Diagnostic
System fo r Primary Care.
All studies were conducted in primary care w ith unselected participants, except
that by Barsky et al,16 which was conducted at a specialty clinic and selected
patients presenting w ith heart palpitations.
a Reported Ns were calculated according to the number o f patients who
completed the criterion standard and not the number enrolled in the study;
age is reported as mean (standard deviation).

yielded sim ilar diagnostic accuracy results across th e sex distribu ­
tio n o f the studies we evaluated (range female, 64% to 85%).
Panic Disorder
We assessed th e heterogeneity o f 4 o f th e 6 studies fo r identifying
pa tie nts w ith panic disorder. One stu d y16 was n o t included be ­
cause it assessed patients w ith palpitations w h o presented to spe­
cialists rather than unselected patients presenting to a prim ary care
provider. A second study19 was n o t included because it had no d i­
agnostic u tility (both LR CIs included 1), so it could not classify the
presence or absence o f panic disorder.
The Patient Health Q uestionnaire (PHQ), using a positive re­
sponse to all 5 questions, had good sensitivity (81%) and specificity
(99% ), th e best LR+ (78; 95% Cl, 29-210), and th e best LR- (0.2 0 ;
95% Cl, 0.11-0.37). The PHQ requires less than 1 m inute fo r com ple­
tion and has an easy literacy level. The SDDS-PC is also efficient, w ith
a sum m ary LR+ o f 4.9 (95% Cl, 3 .0 -7 9 ) and sum m ary LR- o f 0.35
(95% Cl, 0.2 5-0 .4 8 ). An additional advantage o f th e PHQ is th a t it
includes a b rief depression m odule previously found to have high
sensitivity and specificity fo r diagnosing depression.28
The 4 instrum ents had high heterogeneity fo r the LR+ (/2, 92%;
P< .001), b u t th e LR -show ed low heterogeneity (/2, 14%; P = .32).
In a meta-regression, age was not associated w ith the summ ary LR+
(R2, 0 ), suggesting th a t th e results are similar in th e age range we
evaluated (mean age range 39 to 54 years). The meta-regression
showed th a t the sum m ary LR+ accounted fo r a small am ount o f the
variability in the LR+ (R2, 15%; P = .03).
Combined Screening fo r GAD and Panic Disorder
For identifying patients w ho may have either GAD or panic disorder,
the Beck Anxiety Inventory-Primary Care performed well compared
w ith other instruments, w ith an LR+ o f 4.6 (95% Cl, 2.3-8.9) and an
LR- o f 0.19 (95% Cl, 0.05-0.68). The instrum ent has an easy literacy
and can be completed quickly (approximately 1 minute). An alterna­
tive combined instrument, the Primary Care Evaluation o f Mental Dis­
orders, has the fewest number o f questions fo r the patient (3), short

82 JAM A July 2,2014 Volume 312, Number 1 jama.com

Screening fo r Generalized Anxiety or Panic Disorder
completion tim e (1 minute), and easy literacy level. A t a threshold score
o f less than or equal to 1 question w ith a positive response, individu­
als w ith no positive responses have the lowest LR- w ith the narrow­
est Cl fo r either anxiety disorder (LR-, 0.12; 95% Cl, 0.05-0.29).
Discussion
We found th a t 2 screening instruments, GAD-7 fo r GAD and the PHQ
fo r panic disorder, have good perform ance characteristics and are
feasible fo r use in prim ary care. Further validation o f these instru­
ments is needed because neither instrum ent was replicated in more
than 1 prim ary care population.
Study Strengths
This study was a highly structured and system atic review o f the ex­
ta n t evidence. Our evidence synthesis was guided by a carefully de­
signed standardized protocol, including a systematic search o f re­
search d a ta b a se s and re le v a n t b ib lio g ra p h ie s , d o u b le data
abstraction, and use o f validated criteria to assess the quality o f iden­
tifie d studies. Our m ultidisciplinary team included expertise in in­
ternal medicine, primary care, psychiatry, and psychology. Our search
identified a large num ber o f anxiety screening instrum ents, b u t few
had been studied in prim ary care populations. These instrum ents
had m oderate to good operating characteristics, b u t unlike instru­
ments used in the detection o f oth er comm on m ental illnesses such
as depression or dementia, the operating characteristics have not
been replicated in m ultiple samples. Even fortheS D D S -P C -the only
instrum ent evaluated in m ultiple s tu d ie s-th e versions studied were
different, w hich m ight change the te st performance.
Study Limitations
In most studies, threshold values for the screening instrument were
specified after analysis o f results instead o f before. Thus, replication
is needed to validate the cutoffs recommended in these studies. Ad­
ditionally, many o f the studies did not confirm the diagnosis w ith the
reference standard in all patients, or in a random sample o f them, which
could introduce partial verification bias. A fu rth e r lim itation is the lack
o f studies reporting on patient outcomes and societal influence. This
lack o f im portant patient outcomes has been recognized as a chal­
lenge in systematic reviews o f diagnostic tests.29 Because our eligibil­
ity criteria were designed to exclude poor-quality studies (ie, studies
in which the same person conducted the screeningand criterion stan­
dard), we may have excluded studies that could provide low-level evi­
dence on the topic. Furthermore, one o f the better-perform ing mea­
sures, the Beck Anxiety Inventory-Primary Care, was tested in a very
smallsamplefn = 56) and thatstudy17was rated as havingahigher risk
o f bias (quality rating = III). A solution to these issues is to encourage
future high-quality validation studies, which are notably absent de­
spite that many o f them were published almost 20 years ago. The cri­
terion standard fo r GAD and panic disorder has not changed appre­
ciably in that time, and thus the performance characteristics o f these
measures remain applicable to current diagnoses. Finally, these stud­
ies w ere n o t designed to address d iffe rin g perform ance in sub­
groups, so our evaluation o f age and sex as explanations for varying
performance is based on a small number o f studies, uses indirect com ­
parisons, and should be considered exploratory. Indeed, future stud­
ies would benefit from the inclusion o f older patients (>65 years) and
jama.com
The Rational Clinical Examination Clinical Review & Education
more ethnically diverse samples to better determine how these screen­
ing measures perform in different subgroups.
How to Learn a Method for Diagnosing GAD
and Panic Disorder
Both th e GAD-7 and PHQ screening instrum ents are available o n ­
line (www.phqscreeners.com ) and have been translated into many
la n g u a g e s . B e ca u se b o th o f th e s e in s tr u m e n ts a re s e lf-
administered, minimal clinician training is needed to administerthem .
Additional advantages o f GAD-7 are th a t it has good operating char­
acteristics in a 2-item abbreviated version (the GAD-2) and in screen­
ing fo r anxiety disorders other than GAD.4 A manual fo r scoring both
instrum ents is also available online. All o f th e instrum ents included
in this review are fo r screening or case-finding purposes and do not
diagnose GAD or panic disorder. Although these instrum ents may
be used as p a rt o f th e in itia l d ia g n ostic e valuation, a c rite rio n -
based diagnosis m ust be established through fu rth e r evaluation by
a prim ary care physician or by a m ental health professional to whom
th e patient is referred. Such confirm ation should be determ ined by
fo llo w -up questions based on th e DSM-5 (outlined in Table 1) and
should rule o u t psychiatric disorders w ith related sym ptom s (eg,
posttraum atic stress disorder, depression) and medical causes o f
symptoms suggestive o f anxiety. The studies we reviewed used DSM-
III or DSM-IV diagnostic criteria fo r GAD and panic disorder; no sig­
nificant changes in these criteria were introduced in DSM-5.
Treatment
Screening alone is n o t sufficient to ensure th a t patients w ith anxi­
e ty disorders in the prim ary care setting receive appropriate tre a t­
m ent. Although referring a patient fo r a psychiatric evaluation is one
option, prim ary care physicians should also familiarize themselves
w ith the diagnostic criteria fo r GAD and panic disorder, as well as w ith
pharmacologic and other treatm ents for these disorders th a t are ap­
propriate for primary care. Collaborative care models integrating psy­
chiatric trea tm e nt in the prim ary care setting have also been shown
to be effective fo r anxiety disorders.7 Furthermore, because there
is sym ptom overlap between GAD or panic disorder and o th e r psy­
chiatric diagnoses, false-positive results on any o f these screening
instrum ents may be n o t only "true" false-positives (ie, when th e pa­
tie n t meets the criteria fo r no related diagnoses) bu t also due to the
presence o f a related psychiatric disorder. As such, a positive screen­
ing result, even if it is a false-positive fo r GAD or panic disorder, may
indicate th e need fo r fu rth e r evaluation o f th e patient.
Scenario Resolution
You observe th a t Ms B has im p orta n t risk factors fo r an anxiety dis­
order, and her trip to urgent care suggests a possible panic attack.
You decide th a t in addition to checking her blood pressure, you will
conduct case-finding fo r GAD and panic disorders. You adm inister
th e GAD-7 and PHQ, wherein she scores 12 on the GAD-7 and an­
swers no to the PHQ item about anxiety attacks. W ith a pretest prob­
ability o f 20 % fo r GAD (based on an estimate o f tw ice th e preva­
lence in unselected prim ary care patients) and a GAD-7 LR+ o f 5.1,
Ms B. has a 59% p ro b a b ility o f having GAD. A fte r discussing o p ­
tions fo r evaluation and treatm ent, you refer her fo r a psychiatric
evaluation in which her condition may be diagnosed and treated w ith
em p irica lly su p p orte d tre a tm e n ts such as co g n itive behavioral
therapy or an appropriate pharmacotherapy.
JAMA July 2,2014 Volume 312, Number 1 83
 Clinical Review & Education The Rational Clinical Examination
Bottom Line
There are several promising case-finding instruments with good
performance characteristics fo r GAD and panic disorder in p ri­
mary care populations. In particular, the GAD-7 and PHQ stand
out as the most efficient instruments, whereas the SDDS-PC may
be an adequate alternative when a fast screen is desired because
ARTICLE INFORMATION
Author Contributions: Dr Williams had full access
to all o f the data in the study and takes
responsibility fo r the integrity o f the data and the
accuracy o f the data analysis.
Study concept and design: Williams, Benjamin,
McDuffie.
Acquisition, analysis, or interpretation o f data: All
authors.
Drafting o f the manuscript: Herr, Benjamin, McDuffie.
Critical revision o f the manuscript for im portant
intellectual content: Herr, Williams, Benjamin.
Statistical analysis: Herr, Williams, Benjamin.
Obtained funding: Williams.
Administrative, technical, or material support: Herr,
McDuffie.
Study supervision: Williams.
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure o f Potential Conflicts o f Interest and
none were reported.
Funding/Support: This report is based on research
conducted by the Evidence-based Synthesis
Program (ESP) Center, located at the Durham VA
Medical Center, and funded by the Department of
Veterans Affairs, Veterans Health Administration,
Office o f Research and Development, Health
Services Research and Development (VA-ESP
Project 09-010).
Role of the Sponsors: The funding organization
had no role in the design and conduct o f the study:
collection, management, analysis, and
interpretation o f the data; preparation, review, or
approval o f the manuscript; and decision to submit
the manuscript for publication.
Disclaimer: The findings and conclusions in this
article are those o f the authors, who are responsible
fo r its contents; the findings and conclusions do not
necessarily represent the views o f the Department
o f Veterans Affairs or the US government.
Therefore, no statement in this article should be
construed as an official position o f the Department
ofVeterans Affairs,
Additional Contributions: We thank Lori Bastian,
MD, MHS, Padmanabhan Premkumar, MD, Jason
Webb, MD, and Joseph Zanga, MD, for their
valuable comments on previous drafts o f the
manuscript. We also thank Liz Wing, MA, Megan
von Isenburg, MS, and Avishek Nagi, MS, for
assistance w ith manuscript preparation and
literature searching. No one received financial
compensation for his/her contributions.
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84 JAMA July 2,2014 Volume 312, Number 1
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