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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
Why Is This Question Important?
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 A nxiety disorders are prevalent, are o fte n chronic, cause im p o r­
she had a visit to urgent care after having transient chest pain, short­ ta n t functional im pairm ent, and are associated w ith increased health
ness o f breath, and palpitations. Myocardial ischemia was ruled o u t care use.1,2 Two o f the m ore com m on anxiety disorders are gener­
w ith o u t req u irin g hospital adm ission. Female sex, stressful life alized anxiety disorder (GAD) and panic disorder. In co m m u n ity
events, and chronic medical illness place her at increased risk fo r an samples, the estim ated lifetim e prevalence rates fo r GAD and panic
anxiety disorder. W hat tools could be used by th e physician or nurse 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 ing; shortness o f breath; feeling o f choking; chest pain or discom ­
3.1% and 2.3%, respectively.3 Primary care patients have higher rates fo rt; nausea or abdom inal distress; feeling dizzy, unsteady, lig h t­
o f both GAD (8% ) and panic disorder (6.8% ), and th e prevalence headed, o r fa in t; paresthesias; chills; o r h o t flushes.8 A lth o u g h
rate o f GAD increases to 22% among those w ith anxiety problem s agoraphobia was previously considered to be a subtype w ith in the
as th e presenting concern.4,5 Many patients w ith anxiety disorders panic disorder diagnosis, in th e Diagnostic and Statistical Manual o f
present to th e ir prim ary care physician w ith som atic sym ptom s, Mental Disorders (Fifth Edition) (DSM-5) it is now classified as a dis­
which contributes to underrecognition o f these conditions and can crete disorder characterized by avoidance o f public spaces fo r fear
result in unnecessary and costly diagnostic te stin g.6 When diag­ o f having a panic attack.
nosed, both GAD and panic disorder can be treated successfully w ith A clinical evaluation o f anxiety disorders can begin w ith an open-
m ed ica tio n a n d /o r psychotherapy. Furtherm ore, care m anage­ ended question such as "Tell me about your worries, fears, con­
m ent trials have shown th a t screening, coupled w ith effective p ri­ cerns, and stresses, and how th e y affe ct you."9 W hen GAD is in ­
mary care trea tm e nt, improves outcom es fo r patients w ith anxiety quired about specifically, a question such as "Would you say th a t you
disorders.7 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,
How to Diagnose GAD and Panic Disorder
anxious, or very uneasy?"10
A nxiety sym ptom s such as w o rry o r physical tension are exp e ri­ Another approach to th e diagnosis o f GAD and panic disorder
enced nearly universally in response to stressful or threatening situ­ in prim ary care clinics is to ask all patients, or those w ith risk fac­
ations. Anxiety may bean adaptive em otional experience th a t helps tors, to com plete a self-report screening instrum ent. Depending on
a person to avoid or prepare fo r fu tu re challenges. In contrast, anxi­ the prevalence o f th e disease, the physician may w ant to optim ize
ety disorders cause severe and persistent symptoms that impair func­ the positive likelihood ratio (LR+) to avoid unnecessary additional
tioning. The criterion standards fo r GAD and panic disorder are sum ­ testing or the negative likelihood ratio (LR-) to be confident that anxi­
marized in Table 1. Generalized anxiety disorder is characterized by e ty disorders do n o t require additional consideration. An alterna­
at least 6 m onths o f persistent, excessive anxiety or w o rry th a t is tive as part o f the initial diagnostic assessment would be to evalu­
d ifficu lt to control and causes significant distress or im pairm ent. The ate only patients w ho present w ith sym ptom s th a t raise suspicion
diagnosis requires at least 3 o f 6 additional sym ptom s: restless­ o f an anxiety disorder. For routine use in prim ary care settings, the
ness, fatigue, irritability, decreased concentration, muscle tension, ideal instrum ent should be brief, accurate, easy to score and in te r­
and sleep d istu rb a n ce .8 Panic d iso rd e r is characterized by fr e ­ pret, and studied in mixed populations o f patients. For patients w ith
quent and unexpected panic attacks, and individuals w ith this dis­ a positive screening result, a careful clinical interview coupled w ith
order exhibit intense w orry about having them. Panic attacks are pe­ a targeted physical examination and any indicated diagnostic te s t­
riods o f intense fear or te rro r associated w ith autonom ic arousal, and ing to evaluate fo r an underlying explanatory medical illness is re­
typical sym ptom s include palpitations; sweating; tre m b lin g o r shak­ quired fo r a de finitive diagnosis. To inform decision m aking regard-

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

ing a standard instrum ent to assess prim ary care patients fo r anxiety S ta tis tic a l M e th o d s
disorders, w e conducted a system atic review o f th e literature to Sensitivity, specificity, and likelihood ratios (LRs) were calculated w ith
evaluate th e perform ance o f self-report instrum ents used to diag­ CIs fo r instrum ents evaluated in each study. An LR+ is the ratio o f
nose GAD and panic disorder in prim ary care settings. 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
Methods
result in an individual w ith o u t it. Tests w ith higher specificity gen­
Search S tra te g y a n d S tu d y S e le ctio n erally have higher LRs, and positive results are m ost useful fo r iden­
We searched MEDLINE, PsycINFO, and th e Cochrane Library from tify in g patients w ith an anxiety disorder, whereas tests w ith higher
January 1980 through April 2014 fo r studies conducted in general sensitivity generally have lower LRs, and negative results are most
medical settings th a t compared a self-report instrum ent w ith an ac­ useful fo r ruling o u t patients w h o do n o t have an anxiety disorder.
ceptable criterion standard. The search strategy included the term s If an LR+ is 2, a positive test result (in this case, a positive score on
generalized anxiety disorder and panic disorder, th e names o f an anxiety questionnaire) is tw ice as likely to occur in an individual
a n xie ty instrum ents, and a validated search filte r fo r retrie vin g w ith an anxiety disorder as opposed to an individual w ith o u t one.
articles on th e diagnosis o f health disorders (eA ppendix 1 in the An LR- o f 0.2 means th a t a negative screening result is o n e -fifth as
Supplem ent).11,12 Electronic searches were supplem ented by exam­ likely to occur in an individual w ith an anxiety disorder as opposed
ining the bibliographies o f systematic reviews, a recent technical re­ to an individual w ith o u t one. Because GAD and panic disorder are 2
port, and the studies we ultim ately included in the technical report.13 d istin ct clinical entities, w e calculated sum m ary estim ates sepa­
We included studies th a t were conducted w ith patients aged rately fo r studies on GAD-specific instrum ents and panic disorder-
at least 18 years w ho were treated in general medical settings (ie, specific instrum ents.
general internal medicine, fam ily medicine, geriatrics, emergency To estimate th e prior probability o f GAD and panic disorder, we
d e p a rtm e n t, and w om en's health clinic); com pared s e lf-re p o rt calculated a random -effects summ ary measure from th e included
questionnaires fo r GAD o r panic d iso rd e r w ith diagnostic in te r­ studies. The Sym ptom Driven Diagnostic System fo r Primary Care
view s, using c rite ria fro m e ith e r th e Diagnostic and Statistical (SDDS-PC) instrum ent was evaluated in 3 studies, which allowed us
Manual of Mental Disorders (Third Edition) ( DSM-III) o r Interna­ to calculate separate sum m ary measures fo r the sensitivity, speci­
tional Classification o f Diseases, Ninth Revision, o r m ore recent ficity, and LR w ith 95% CL All o th er instrum ents were evaluated in
editions o f these publications; and were peer-reviewed, English- only 1 study, fo r which we show th e test's p o in t estim ate and 95%
language publications from North America, western Europe, New CL We explored heterogeneity among the studies w ith Cochran Q
Zealand, o r Australia. Geographic and language lim ita tio ns were and I2, which describe the percentage o f to ta l variation across stu d ­
designed to id e n tify studies w ith th e highest a p p lica b ility to US ies due to heterogeneity rather than chance, and we used m eta ­
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 regression to evaluate the effe ct o f age and sex on th e LRs. Fletero-
abstract fo r relevance. Next, fu ll-te x t articles id e ntified by either geneity was categorized as low, m oderate, o r high according to I2
review er as p o te n tia lly relevant w ere exam ined by 2 reviewers, values o f 25%, 50% , and 75%, respectively. We used Com prehen­
w ho evaluated the articles' e ligibility according to predeterm ined sive Meta-Analysis (Biostat version 2.2 .06 4 ) fo r all meta-analyses.
criteria (eA ppendix 2 in th e Supplem ent). Disagreem ents were
resolved by discussion or a th ird reviewer.

Results
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 S tu d y C h a ra cte ristics
lined by the Standards fo r Reporting o f Diagnostic Accuracy.14These We id entified 3 6 0 5 unique citations fro m a com bined electronic
elements included descriptors to assess applicability (eg, setting, search ofMEDLINE via PubM ed(n = 1167), PsycINFO (n = 1810),and
sample characteristics, anxiety disorder prevalence), test p e rfo r­ the Cochrane Library (n = 6 0 5 ) and from a manual examination o f
mance, and q u ality (eg, recru itm en t m ethod, blinding, reference references (n = 23). A fte r inclusion and exclusion criteria were ap­
standard, sample size) o f each study. When provided, raw data for plied, 3529 articles were excluded at th e title and abstract level. We
the 2 x 2 table were extracted, and when n o t provided, data were retrieved 76 articles fo r fu ll-te x t review and excluded 63. For data
derived from oth er perform ance characteristics such as sensitivity abstraction and evidence synthesis, w e retained a to ta l o f 13 ar­
and specificity. When results w ere adjusted fo r th e sampling de­ ticles representing 10 unique studies.16'25 Because some studies in ­
sign (eg, partial verification o f the criterion-based diagnosis), we use cluded more than 1sample or evaluated more than 1 instrum ent, we
th e adjusted results. A second review er verified all data abstrac­ included 14 unique evaluations o f anxiety instrum ents. The eFigure
tions, and disagreements were resolved by review er discussion or in th e Supplem ent illustrates the literature search process.
by obtaining a th ird reviewer's opinion. O f 13 articles describing 10 studies, 9 d ifferent instrum ents were
For each selected study, raters com pleted th e Q uality Assess­ evaluated (Table 2). Across all studies, diagnostic interview s d e ter­
m ent o f Diagnostic Accuracy Studies, a 14-item to o l th a t assesses m ined th a t 257 o f 2785 patients assessed had a diagnosis o f GAD
study quality (eAppendixes 3-4 in the Supplement). We followed rec­ w hile 224 o f 2637 patients assessed had a diagnosis o f panic disor­
om m endations from The Rational Clinical Examination series15 by der. The average age o f patients in studies o f GAD (n = 6) (Table 3)
assigninga level o f evidence for each study, rangingfrom I (high qual­ was sim ilar across 5 o f th e samples18,21,23,25 (range, 38-47 years),
ity) to V (low quality). whereas 1 study20 contained older patients (mean age, 73 years).

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

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

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

completion tim e (1 minute), and easy literacy level. A t a threshold score more ethnically diverse samples to better determine how these screen­
o f less than or equal to 1 question w ith a positive response, individu­ ing measures perform in different subgroups.
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). 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
Discussion
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-
We found th a t 2 screening instruments, GAD-7 fo r GAD and the PHQ administered, minimal clinician training is needed to administerthem .
fo r panic disorder, have good perform ance characteristics and are Additional advantages o f GAD-7 are th a t it has good operating char­
feasible fo r use in prim ary care. Further validation o f these instru­ acteristics in a 2-item abbreviated version (the GAD-2) and in screen­
ments is needed because neither instrum ent was replicated in more ing fo r anxiety disorders other than GAD.4 A manual fo r scoring both
than 1 prim ary care population. 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
Study Strengths diagnose GAD or panic disorder. Although these instrum ents may
This study was a highly structured and system atic review o f the ex­ 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 -
ta n t evidence. Our evidence synthesis was guided by a carefully de­ based diagnosis m ust be established through fu rth e r evaluation by
signed standardized protocol, including a systematic search o f re­ a prim ary care physician or by a m ental health professional to whom
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 th e patient is referred. Such confirm ation should be determ ined by
abstraction, and use o f validated criteria to assess the quality o f iden­ fo llo w -up questions based on th e DSM-5 (outlined in Table 1) and
tifie d studies. Our m ultidisciplinary team included expertise in in­ should rule o u t psychiatric disorders w ith related sym ptom s (eg,
ternal medicine, primary care, psychiatry, and psychology. Our search posttraum atic stress disorder, depression) and medical causes o f
identified a large num ber o f anxiety screening instrum ents, b u t few symptoms suggestive o f anxiety. The studies we reviewed used DSM-
had been studied in prim ary care populations. These instrum ents III or DSM-IV diagnostic criteria fo r GAD and panic disorder; no sig­
had m oderate to good operating characteristics, b u t unlike instru­ nificant changes in these criteria were introduced in DSM-5.
ments used in the detection o f oth er comm on m ental illnesses such
as depression or dementia, the operating characteristics have not Treatment
been replicated in m ultiple samples. Even fortheS D D S -P C -the only Screening alone is n o t sufficient to ensure th a t patients w ith anxi­
instrum ent evaluated in m ultiple s tu d ie s-th e versions studied were e ty disorders in the prim ary care setting receive appropriate tre a t­
different, w hich m ight change the te st performance. m ent. Although referring a patient fo r a psychiatric evaluation is one
option, prim ary care physicians should also familiarize themselves
Study Limitations w ith the diagnostic criteria fo r GAD and panic disorder, as well as w ith
In most studies, threshold values for the screening instrument were pharmacologic and other treatm ents for these disorders th a t are ap­
specified after analysis o f results instead o f before. Thus, replication propriate for primary care. Collaborative care models integrating psy­
is needed to validate the cutoffs recommended in these studies. Ad­ chiatric trea tm e nt in the prim ary care setting have also been shown
ditionally, many o f the studies did not confirm the diagnosis w ith the to be effective fo r anxiety disorders.7 Furthermore, because there
reference standard in all patients, or in a random sample o f them, which is sym ptom overlap between GAD or panic disorder and o th e r psy­
could introduce partial verification bias. A fu rth e r lim itation is the lack chiatric diagnoses, false-positive results on any o f these screening
o f studies reporting on patient outcomes and societal influence. This instrum ents may be n o t only "true" false-positives (ie, when th e pa­
lack o f im portant patient outcomes has been recognized as a chal­ tie n t meets the criteria fo r no related diagnoses) bu t also due to the
lenge in systematic reviews o f diagnostic tests.29 Because our eligibil­ presence o f a related psychiatric disorder. As such, a positive screen­
ity criteria were designed to exclude poor-quality studies (ie, studies ing result, even if it is a false-positive fo r GAD or panic disorder, may
in which the same person conducted the screeningand criterion stan­ indicate th e need fo r fu rth e r evaluation o f th e patient.
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 Scenario Resolution
sures, the Beck Anxiety Inventory-Primary Care, was tested in a very You observe th a t Ms B has im p orta n t risk factors fo r an anxiety dis­
smallsamplefn = 56) and thatstudy17was rated as havingahigher risk order, and her trip to urgent care suggests a possible panic attack.
o f bias (quality rating = III). A solution to these issues is to encourage You decide th a t in addition to checking her blood pressure, you will
future high-quality validation studies, which are notably absent de­ conduct case-finding fo r GAD and panic disorders. You adm inister
spite that many o f them were published almost 20 years ago. The cri­ th e GAD-7 and PHQ, wherein she scores 12 on the GAD-7 and an­
terion standard fo r GAD and panic disorder has not changed appre­ swers no to the PHQ item about anxiety attacks. W ith a pretest prob­
ciably in that time, and thus the performance characteristics o f these ability o f 20 % fo r GAD (based on an estimate o f tw ice th e preva­
measures remain applicable to current diagnoses. Finally, these stud­ lence in unselected prim ary care patients) and a GAD-7 LR+ o f 5.1,
ies w ere n o t designed to address d iffe rin g perform ance in sub­ Ms B. has a 59% p ro b a b ility o f having GAD. A fte r discussing o p ­
groups, so our evaluation o f age and sex as explanations for varying tions fo r evaluation and treatm ent, you refer her fo r a psychiatric
performance is based on a small number o f studies, uses indirect com ­ evaluation in which her condition may be diagnosed and treated w ith
parisons, and should be considered exploratory. Indeed, future stud­ em p irica lly su p p orte d tre a tm e n ts such as co g n itive behavioral
ies would benefit from the inclusion o f older patients (>65 years) and therapy or an appropriate pharmacotherapy.

jama.com JAMA July 2,2014 Volume 312, Number 1 83


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

it assesses both conditions with relatively few questions. For clini­


Bottom Line cal practices tha t opt for patient-com pleted screening instru­
ments (eg, in the waiting room), the Primary Care Evaluation of
There are several promising case-finding instruments with good Mental Disorders shows promise fo r id en tifying anxiety tha t
performance characteristics fo r GAD and panic disorder in p ri­ might prom pt additional questions during an examination. Fur­
mary care populations. In particular, the GAD-7 and PHQ stand ther replication o f these initial validation studies, in particular
out as the most efficient instruments, whereas the SDDS-PC may w ith samples o f older and more ethnically diverse patients, is
be an adequate alternative when a fast screen is desired because needed in primary care settings.

ARTICLE INFORMATION unrecognized anxiety disorders and major depressive 15. Simel DL. Update: primer on precision and
Author Contributions: Dr Williams had full access disorder. J Affect Disord. 1997;43(2):105-119. accuracy. In: Simel DL, Rennie D, Keitz SA, eds. The
to all o f the data in the study and takes 3. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime Rational Clinical Examination: Evidence-Based Clinical
responsibility fo r the integrity o f the data and the and 12-month prevalence o f DSM-lll-R psychiatric Diagnosis. New York, NY: McGraw Hill; 2009:9-16.
accuracy o f the data analysis. disorders in the United States: results from the 16. Barsky AJ, Ahern DK, Delamater BA, Clancy SA,
Study concept and design: Williams, Benjamin, National Comorbidity Survey. Arch Gen Psychiatry. Bailey ED. Differential diagnosis o f palpitations:
McDuffie. 1994;51(1):8-19. preliminary development o f a screening
Acquisition, analysis, or interpretation o f data: All instrument. Arch Fam Med. 1997;6(3):241-245.
4. Kroenke K, Spitzer RL, Williams JB, Monahan
authors.
PO, Lowe B. Anxiety disorders in primary care: 17. Beck AT, Steer RA. Ball R, Ciervo CA, Kabat M.
Drafting o f the manuscript: Herr, Benjamin, McDuffie.
prevalence, impairment, comorbidity, and Use o f the Beck Anxiety and Depression Inventories
Critical revision o f the manuscript for im portant
detection. Ann Intern Med. 2007;146(5):317-325. for primary care w ith medical outpatients.
intellectual content: Herr, Williams, Benjamin.
5. Wittchen HU. Generalized anxiety disorder: Assessment. 1997;4(3):211-219.
Statistical analysis: Herr, Williams, Benjamin.
Obtained funding: Williams. prevalence, burden, and cost to society. Depress 18. Broadhead WE, Leon AC, Weissman MM, e tal.
Administrative, technical, or material support: Herr, Anxiety. 2002;16(4):162-171. Development and validation o f the SDDS-PC screen
McDuffie. 6. Zaubler TS, Katon W. Panic disorder in the general fo r m ultiple mental disorders in primary care. Arch
Study supervision: Williams. medical setting. J Psychosom Res. 1998;44(l):25-42. Fam Med. 1995;4(3):211-219.

Conflict of Interest Disclosures: All authors have 7. Woltmann E, Grogan-Kaylor A, Perron B, et al. 19. Johnson MR, Hartzema AG, Mills TL, et al. Ethnic
completed and submitted the ICMJE Form for Comparative effectiveness o f collaborative chronic differences in the reliability and validity o f a panic
Disclosure o f Potential Conflicts o f Interest and care models fo r mental health conditions across disorder screen. Ethn Health. 2007;12(3):283-296.
none were reported. primary, specialty, and behavioral health care 2 0 . Krasucki C, Ryan P, Ertan T, Howard R, Lindesay
Funding/Support: This report is based on research settings: systematic review and meta-analysis. Am J J, Mann A. The FEAR: a rapid screening instrument
conducted by the Evidence-based Synthesis Psychiatry. 2012;169(8):790-804. for generalized anxiety in elderly primary care
Program (ESP) Center, located at the Durham VA 8. American Psychiatric Association. Diagnostic attenders. In tJ Geriatr Psychiatry. 1999;14(1):60-68.
Medical Center, and funded by the Department of and Statistical Manual o f Mental Disorders: DSM-5. 21. Leon AC, Olfson M, Weissman MM, et al. Brief
Veterans Affairs, Veterans Health Administration, 5th ed. Washington, DC: American Psychiatric screens fo r mental disorders in primary care. J Gen
Office o f Research and Development, Health Association; 2013. Intern Med. 1996;ll(7):426-430.
Services Research and Development (VA-ESP
9. Zaroukian MH, Kotaru VP. Anxiety. In: 22 . Spitzer RL, Kroenke K, Williams JB; Patient
Project 09-010).
Henderson MC, Tierney LM, Smetena GW, eds. The Health Questionnaire Primary Care Study Group.
Role of the Sponsors: The funding organization Complete Patient History: An Evidence-Based Validation and utility o f a self-report version o f
had no role in the design and conduct o f the study: Approach to Differential Diagnosis. 2nd ed. Lange PRIME-MD. JAMA. 1999;282(18):1737-1744.
collection, management, analysis, and Medical Books/McGraw Hill; 2012.
23 . Spitzer RL, Kroenke K, Williams JB, Lowe B. A
interpretation o f the data; preparation, review, or
10 . Means-Christensen AJ, Sherbourne CD, brief measure fo r assessing generalized anxiety
approval o f the manuscript; and decision to submit
Roy-Byrne PP, Craske MG, Stein MB. Using five disorder: the GAD-7. Arch Intern Med. 2006:166
the manuscript for publication.
questions to screen fo r five common mental (10):1092-1097.
Disclaimer: The findings and conclusions in this disorders in primary care: diagnostic accuracy o f
24 . Spitzer RL, Williams JB, Kroenke K, et al. U tility
article are those o f the authors, who are responsible the Anxiety and Depression Detector. Gen Hasp
o f a new procedure for diagnosing mental disorders
fo r its contents; the findings and conclusions do not Psychiatry. 2006;28(2):108-118.
in primary care: the PRIME-MD 1 000 study. JAMA.
necessarily represent the views o f the Department
11. Wilczynski NL, Haynes RB; Hedges Team. 1994;272(22):1749-1756.
o f Veterans Affairs or the US government.
EMBASE search strategies for identifying
Therefore, no statement in this article should be 25 . Moore MT, Anderson NL, Barnes JM, Haigh EA,
methodologically sound diagnostic studies fo r use
construed as an official position o f the Department Fresco DM. Using the GAD-Q-IV to identify
by clinicians and researchers. BMC Med. 2005;3:7.
ofVeterans Affairs, generalized anxiety disorder in psychiatric
12. Haynes RB, Wilczynski NL. Optimal search treatm ent seeking and primary care medical
Additional Contributions: We thank Lori Bastian,
strategies for retrieving scientifically strong studies samples. J Anxiety Disord. 2014;28(1):25-30.
MD, MHS, Padmanabhan Premkumar, MD, Jason
o f diagnosis from Medline: analytical survey. BMJ.
Webb, MD, and Joseph Zanga, MD, for their 26 . Lindesay J, Briggs K, Murphy E. The Guy's/Age
2004;328(7447):1040.
valuable comments on previous drafts o f the Concern survey. Prevalence rates o f cognitive
manuscript. We also thank Liz Wing, MA, Megan 13. Benjamin S, Herr NR, McDuffie J, et al. impairment, depression and anxiety in an urban
von Isenburg, MS, and Avishek Nagi, MS, for Performance characteristics o f self-report elderly community. BrJ Psychiatry. 1989;155:317-329.
assistance w ith manuscript preparation and instruments for diagnosing generalized anxiety and
27. A pfeldorf WJ, Shear MK, Leon AC. Portera L. A
literature searching. No one received financial panic disorders in primary care: a systematic
brief screen fo r panic disorder. J Anxiety Disord.
compensation for his/her contributions. review, http://www.hsrd.research.va.gov
l994;8(1):71-78.
/publications/esp/anxiety-panic.cfm#
.UgOKjNuF-YA. Accessed August 15,2013. 28. Williams JW Jr, Noel PH, Cordes JA, Ramirez G,
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