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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
IMPORTANCE In primary care settings, generalized anxiety disorder (GAD) and panic disorder
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are common but underrecognized illnesses. Identifying accurate and feasible screening
instruments for GAD and panic disorder has the potential to improve detection and facilitate
treatment.
CME Quiz at
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CME Questions page 89
OBJECTIVE To systematically review the accuracy of self-report screening instruments in
diagnosing GAD and panic disorder in adults.
DATA SOURCES We searched MEDLINE, PsycINFO, and the Cochrane Library for relevant
articles published from 1980 through April 2014.
STUDY SELECTION Prospective studies of diagnostic accuracy that compared a self-report
screening instrument for GAD or panic disorder with the diagnosis made by a trained clinician
using Diagnostic and Statistical Manual of Mental Disorders or International Classification of
Diseases criteria.
RESULTS We screened 3605 titles, excluded 3529, and performed a more detailed review of
76 articles. We identified 9 screening instruments based on 13 articles from 10 unique studies
for the detection of GAD and panic disorder in primary care patients Across all studies,
diagnostic interviews determined that 257 of 2785 patients assessed had a diagnosis of GAD
while 224 of 2637 patients assessed had a diagnosis of panic disorder. The best-performing
test for GAD was the Generalized Anxiety Disorder Scale 7 Item (GAD-7), with a positive
likelihood ratio of 5.1 (95% CI, 4.3-6.0) and a negative likelihood ratio of 0.13 (95% CI,
0.07-0.25). The best-performing test for panic disorder was the Patient Health
Questionnaire, with a positive likelihood ratio of 78 (95% CI, 29-210) and a negative
likelihood ratio of 0.20 (95% CI, 0.11-0.37).
CONCLUSIONS AND RELEVANCE Two screening instruments, the GAD-7 for GAD and the
Patient Health Questionnaire for panic disorder, have good performance characteristics and
are feasible for use in primary care. However, further validation of these instruments is
needed because neither instrument was replicated in more than 1 primary care population.
JAMA. 2014;312(1):78-84. doi:10.1001/jama.2014.5950
Corresponding Author: John W.
Williams Jr, MD, MHSc, 411 W Chapel
Hill St, Ste 500, Durham, NC 27701
([email protected]).
Section Editors: David L. Simel, MD,
MHS, Durham Veterans Affairs
Medical Center and Duke University
Medical Center, Durham, NC; Edward
H. Livingston, MD, Deputy Editor.
to determine whether Ms B’s symptoms and related behaviors indicate an anxiety disorder?
Clinical Scenario
Ms B is a 42-year-old computer programmer with a history of irritable bowel syndrome who presents to her primary care physician
for a blood pressure check. Six months ago, she began caring for her
chronically ill mother, and she reports increased stress. You note that
she had a visit to urgent care after having transient chest pain, shortness of breath, and palpitations. Myocardial ischemia was ruled out
without requiring hospital admission. Female sex, stressful life
events, and chronic medical illness place her at increased risk for an
anxiety disorder. What tools could be used by the physician or nurse
78
Author Affiliations: Department of
Psychology, American University,
Washington, DC (Herr); Durham
Veterans Affairs Evidence-based
Synthesis Program (ESP) Center,
Durham, North Carolina (Williams,
McDuffie); Duke University
Department of Medicine, Durham,
North Carolina (Williams, McDuffie);
Grand River Hospital, Kitchener,
Ontario, Canada (Benjamin);
Department of Psychiatry and
Behavioral Neurosciences, McMaster
University, Hamilton, Ontario, Canada
(Benjamin).
Why Is This Question Important?
Anxiety disorders are prevalent, are often chronic, cause important functional impairment, and are associated with increased health
care use.1,2 Two of the more common anxiety disorders are generalized anxiety disorder (GAD) and panic disorder. In community
samples, the estimated lifetime prevalence rates for GAD and panic
disorder are 5.1% and 3.5%, respectively, and 12-month rates (ex-
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Screening for Generalized Anxiety or Panic Disorder
The Rational Clinical Examination Clinical Review & Education
Table 1. Diagnostic Criteria for Generalized Anxiety and Panic Disordera
Main Symptoms
Associated Symptoms
Functional Qualifier
Exclusions
Individuals with GAD often experience
Trembling/shakiness
Muscle aches
Sweating/nausea/diarrhea
Irritable bowel
Headaches
Significant
impairment in
functioning
Not due to another Axis I illness,
medical illness, or substance
(drug of abuse or medication)
Panic attacks are an abrupt surge in
symptoms, including
Palpitations
Sweating
Trembling/shaking
Shortness of breath/choking
Chest pain
Nausea
Dizziness
Chills/heat sensations
Paresthesias
Derealization
Fear of losing control
Fear of dying
Significant
impairment in
functioning
Not due to another Axis I illness,
medical illness, or substance
(drug of abuse or medication)
GAD (DSM-5)
Excessive worry and difficulty controlling worry
for at least 6 mo
≥3 of the following symptoms:
Restlessness
Easily fatigued
Irritability
Difficulty concentrating
Muscle tension
Sleep disturbance
Panic Disorder (DSM-5)
Recurrent and unexpected panic attacks
At least 1 mo of ≥1 of the following symptoms:
Persistent concern about having another attack
Significant maladaptive change in behavior
related to attacks
Abbreviations: DSM, Diagnostic and Statistical Manual of Mental Disorders; GAD,
generalized anxiety disorder.
a
exception: the DSM-5 no longer asks diagnosticians to determine whether
panic disorder is with or without agoraphobia.
The DSM-5 criteria for these disorders are identical to those of DSM-IV, with 1
perienced anytime within the last 12 months, including currently) are
3.1% and 2.3%, respectively.3 Primary care patients have higher rates
of both GAD (8%) and panic disorder (6.8%), and the prevalence
rate of GAD increases to 22% among those with anxiety problems
as the presenting concern.4,5 Many patients with anxiety disorders
present to their primary care physician with somatic symptoms,
which contributes to underrecognition of these conditions and can
result in unnecessary and costly diagnostic testing.6 When diagnosed, both GAD and panic disorder can be treated successfully with
medication and/or psychotherapy. Furthermore, care management trials have shown that screening, coupled with effective primary care treatment, improves outcomes for patients with anxiety
disorders.7
How to Diagnose GAD and Panic Disorder
Anxiety symptoms such as worry or physical tension are experienced nearly universally in response to stressful or threatening situations. Anxiety may be an adaptive emotional experience that helps
a person to avoid or prepare for future challenges. In contrast, anxiety disorders cause severe and persistent symptoms that impair functioning. The criterion standards for GAD and panic disorder are summarized in Table 1. Generalized anxiety disorder is characterized by
at least 6 months of persistent, excessive anxiety or worry that is
difficult to control and causes significant distress or impairment. The
diagnosis requires at least 3 of 6 additional symptoms: restlessness, fatigue, irritability, decreased concentration, muscle tension,
and sleep disturbance.8 Panic disorder is characterized by frequent and unexpected panic attacks, and individuals with this disorder exhibit intense worry about having them. Panic attacks are periods of intense fear or terror associated with autonomic arousal, and
typical symptoms include palpitations; sweating; trembling or shak-
ing; shortness of breath; feeling of choking; chest pain or discomfort; nausea or abdominal distress; feeling dizzy, unsteady, lightheaded, or faint; paresthesias; chills; or hot flushes.8 Although
agoraphobia was previously considered to be a subtype within the
panic disorder diagnosis, in the Diagnostic and Statistical Manual of
Mental Disorders (Fifth Edition) (DSM-5) it is now classified as a discrete disorder characterized by avoidance of public spaces for fear
of having a panic attack.
A clinical evaluation of anxiety disorders can begin with an openended question such as “Tell me about your worries, fears, concerns, and stresses, and how they affect you.”9 When GAD is inquired about specifically, a question such as “Would you say that you
have been bothered by ‘nerves’ or feeling anxious or on edge?” can
elicit symptoms of the disorder. When inquiring about panic disorder specifically, the clinician can ask a question such as “Did you ever
have a spell or an attack when all of a sudden you felt frightened,
anxious, or very uneasy?”10
Another approach to the diagnosis of GAD and panic disorder
in primary care clinics is to ask all patients, or those with risk factors, to complete a self-report screening instrument. Depending on
the prevalence of the disease, the physician may want to optimize
the positive likelihood ratio (LR+) to avoid unnecessary additional
testing or the negative likelihood ratio (LR−) to be confident that anxiety disorders do not require additional consideration. An alternative as part of the initial diagnostic assessment would be to evaluate only patients who present with symptoms that raise suspicion
of an anxiety disorder. For routine use in primary care settings, the
ideal instrument should be brief, accurate, easy to score and interpret, and studied in mixed populations of patients. For patients with
a positive screening result, a careful clinical interview coupled with
a targeted physical examination and any indicated diagnostic testing to evaluate for an underlying explanatory medical illness is required for a definitive diagnosis. To inform decision making regard-
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79
Clinical Review & Education The Rational Clinical Examination
ing a standard instrument to assess primary care patients for anxiety
disorders, we conducted a systematic review of the literature to
evaluate the performance of self-report instruments used to diagnose GAD and panic disorder in primary care settings.
Methods
Search Strategy and Study Selection
We searched MEDLINE, PsycINFO, and the Cochrane Library from
January 1980 through April 2014 for studies conducted in general
medical settings that compared a self-report instrument with an acceptable criterion standard. The search strategy included the terms
generalized anxiety disorder and panic disorder, the names of
anxiety instruments, and a validated search filter for retrieving
articles on the diagnosis of health disorders (eAppendix 1 in the
Supplement).11,12 Electronic searches were supplemented by examining the bibliographies of systematic reviews, a recent technical report, and the studies we ultimately included in the technical report.13
We included studies that were conducted with patients aged
at least 18 years who were treated in general medical settings (ie,
general internal medicine, family medicine, geriatrics, emergency
department, and women’s health clinic); compared self-report
questionnaires for GAD or panic disorder with diagnostic interviews, using criteria from either the Diagnostic and Statistical
Manual of Mental Disorders (Third Edition) (DSM-III) or International Classification of Diseases, Ninth Revision, or more recent
editions of these publications; and were peer-reviewed, Englishlanguage publications from North America, western Europe, New
Zealand, or Australia. Geographic and language limitations were
designed to identify studies with the highest applicability to US
populations. Two reviewers independently examined each
abstract for relevance. Next, full-text articles identified by either
reviewer as potentially relevant were examined by 2 reviewers,
who evaluated the articles’ eligibility according to predetermined
criteria (eAppendix 2 in the Supplement). Disagreements were
resolved by discussion or a third reviewer.
Data Abstraction and Quality Ratings
We extracted selected data elements informed by the principles outlined by the Standards for Reporting of Diagnostic Accuracy.14 These
elements included descriptors to assess applicability (eg, setting,
sample characteristics, anxiety disorder prevalence), test performance, and quality (eg, recruitment method, blinding, reference
standard, sample size) of each study. When provided, raw data for
the 2 × 2 table were extracted, and when not provided, data were
derived from other performance characteristics such as sensitivity
and specificity. When results were adjusted for the sampling design (eg, partial verification of the criterion-based diagnosis), we use
the adjusted results. A second reviewer verified all data abstractions, and disagreements were resolved by reviewer discussion or
by obtaining a third reviewer’s opinion.
For each selected study, raters completed the Quality Assessment of Diagnostic Accuracy Studies, a 14-item tool that assesses
study quality (eAppendixes 3-4 in the Supplement). We followed recommendations from The Rational Clinical Examination series15 by
assigning a level of evidence for each study, ranging from I (high quality) to V (low quality).
80
Screening for Generalized Anxiety or Panic Disorder
Statistical Methods
Sensitivity, specificity, and likelihood ratios (LRs) were calculated with
CIs for instruments evaluated in each study. An LR+ is the ratio of
the likelihood of a positive test result in an individual with the condition to the likelihood of a positive test result in an individual without it. An LR− is the ratio of the likelihood of a negative test result in
an individual with the condition to the likelihood of a negative test
result in an individual without it. Tests with higher specificity generally have higher LRs, and positive results are most useful for identifying patients with an anxiety disorder, whereas tests with higher
sensitivity generally have lower LRs, and negative results are most
useful for ruling out patients who do not have an anxiety disorder.
If an LR+ is 2, a positive test result (in this case, a positive score on
an anxiety questionnaire) is twice as likely to occur in an individual
with an anxiety disorder as opposed to an individual without one.
An LR− of 0.2 means that a negative screening result is one-fifth as
likely to occur in an individual with an anxiety disorder as opposed
to an individual without one. Because GAD and panic disorder are 2
distinct clinical entities, we calculated summary estimates separately for studies on GAD-specific instruments and panic disorder–
specific instruments.
To estimate the prior probability of GAD and panic disorder, we
calculated a random-effects summary measure from the included
studies. The Symptom Driven Diagnostic System for Primary Care
(SDDS-PC) instrument was evaluated in 3 studies, which allowed us
to calculate separate summary measures for the sensitivity, specificity, and LR with 95% CI. All other instruments were evaluated in
only 1 study, for which we show the test’s point estimate and 95%
CI. We explored heterogeneity among the studies with Cochran Q
and I2, which describe the percentage of total variation across studies due to heterogeneity rather than chance, and we used metaregression to evaluate the effect of age and sex on the LRs. Heterogeneity was categorized as low, moderate, or high according to I2
values of 25%, 50%, and 75%, respectively. We used Comprehensive Meta-Analysis (Biostat version 2.2.064) for all meta-analyses.
Results
Study Characteristics
We identified 3605 unique citations from a combined electronic
search of MEDLINE via PubMed (n = 1167), PsycINFO (n = 1810), and
the Cochrane Library (n = 605) and from a manual examination of
references (n = 23). After inclusion and exclusion criteria were applied, 3529 articles were excluded at the title and abstract level. We
retrieved 76 articles for full-text review and excluded 63. For data
abstraction and evidence synthesis, we retained a total of 13 articles representing 10 unique studies.16-25 Because some studies included more than 1 sample or evaluated more than 1 instrument, we
included 14 unique evaluations of anxiety instruments. The eFigure
in the Supplement illustrates the literature search process.
Of 13 articles describing 10 studies, 9 different instruments were
evaluated (Table 2). Across all studies, diagnostic interviews determined that 257 of 2785 patients assessed had a diagnosis of GAD
while 224 of 2637 patients assessed had a diagnosis of panic disorder. The average age of patients in studies of GAD (n = 6) (Table 3)
was similar across 5 of the samples18,21,23,25 (range, 38-47 years),
whereas 1 study20 contained older patients (mean age, 73 years).
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Screening for 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
Instrument
No. of
Items
Response Format
Time
Frame
Score
Range
Usual Cut
Point
Literacy
Levelsa
Completion Time
Tracking of
Symptoms
GAD
ADS-GA26
11
Yes or no
Unknown
0-11
4-5
Unknown
Unknown
GAD-723
7
4 Frequency ratings:
not at all, several days,
more than half the days,
nearly every day
2 wk
0-21
Average
5 = mild
10 = moderate
15 = severe
Unknown
Unknown
GAD-Q-IV25
9
5 Yes or no; 2 Likert
(9 response choices);
1 count of worries;
1 physical symptom
checklist
6 mo
0-12
≥5.7
Average
Unknown
Unknown
SDDS-PC18
4 GAD
Yes or no
6 mo
0-5
Unclear
Easy
<2 min
Yes (scale has
separate
longitudinal
tracking module)
Easy
Panic Disorder
BPDS27
4
Symptom severity: very
little, a little, some,
much, very much
None
0-16
≥11
Average
Unknown
Unknown
PHQ22 (panic module
from 3-page
diagnostic form)b
5
Yes or no
4 wk
0-5
Yes on all 5
questions
Easy
<1 min for 42%
1-2 min for 43%
3-5 min for 13%
>5 min for 3%
No
SDDS-PC18
Yes or no
Past mo
0-5
Unclear
Easy
<2 min
10
Symptom severity: not at all,
a little bit, moderately,
quite a bit, a great deal
Unknown
0-50
>21
Average
Unknown
Unknown
BAI-PC17
(GAD and panic)
7
4 Items of symptom severity
Past 2 wk
to today
0-21
≥5
Easy
≈1 min
Unknown
PRIME-MD24(Multiple
components with
GAD and panic)
3
Yes or no
Past mo
0-3
≥1
Easy
<1 min
No
Unnamed 10-item
scale16
5 Panic
GAD or Panic Disorder
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 of Mental Disorders; SDDS-PC, Symptom
Driven Diagnostic System for Primary Care.
a
Easy indicates third- to fifth-grade reading level; average, sixth- to ninth-grade
reading level.
b
The PHQ has been revised such that the fifth question in the panic module has
11 subitems; current scoring requires a yes response to the first 4 questions
and yes to ⱖ4 of 11 subitems for question 5.
The studies were similar in sex, with 64% to 85% women. The studies of panic disorder (n = 6) (Table 3) among unselected patients included participants with a more homogeneous age (mean range,
39-54 years), with a similar distribution of women (66%-72%). A
study of patients presenting with palpitations included similarly aged
participants (mean age, 47 years), with a slightly smaller proportion of women (57%).16
Most studies were rated low risk of bias (Table 3, eAppendixes
3-4). All of the questionnaires were self-administered and did not
require specialized equipment or trained personnel, making them
suitable for patients to complete in a variety of settings. Based on
diagnostic interviews, the random-effects summary estimate for
prevalence of GAD was 10.1% (95% CI, 5.7%-17%), whereas prevalence of panic disorder was 8.8% (95% CI, 6.6%-12%). The panic disorder range does not include the results of Barsky et al,16 which found
a panic disorder prevalence of 26% among patients presenting with
a complaint of heart palpitations.
specificity (83%), had the highest LR+ (5.1; 95% CI, 4.3-6.0), and is
also the only measure that reported test-retest reliability (intraclass correlation, 0.83). A GAD-7 score less than 10 had an LR− (0.13;
95% CI, 0.07-0.26) similar to that of the Generalized Anxiety Disorder Questionnaire Fourth Edition at a threshold less than 5.7 (LR−,
0.18; 95% CI, 0.06-0.52; P = .65 for the comparison). The SDDS-PC
takes less than 2 minutes for completion and has an “easy” literacy
level with 3 different formulations evaluated in differing populations (summary LR+, 2.6 [95% CI, 1.6-4.1]; LR−, 0.31 [95% CI, 0.220.43]). The Anxiety Disorder Scale–Generalized Anxiety was studied in older patients (mean age 72 years) and had the least useful
LR−, 0.70 (95% CI, 0.45-1.1).
The instruments18,20,21,23,25 showed high heterogeneity (LR+:
2
I = 93%, P < .001; LR−: I2 = 76%, P = .001) among studies conducted in primary care with unselected patients. Although metaregression revealed that the LR+ did not vary by the mean age in the
study samples (P = .23), older mean age was strongly associated with
the LR−, accounting for 94% of the heterogeneity (P < .001). Studies of GAD with a higher frequency of younger patients found a lower
LR− (easier to rule out GAD) compared with studies with older patients. Sex accounted for only 29% of the heterogeneity in the summary LR+ (P < .22) and only 5% of the heterogeneity in the summary LR− (P = .43). Thus, these screening instruments for GAD
Performance Characteristics of Self-report
Screening Instruments
Generalized Anxiety Disorder
The Generalized Anxiety Disorder Scale 7 Item (GAD-7), using a cut
point of greater than or equal to 10, had good sensitivity (89%) and
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Clinical Review & Education The Rational Clinical Examination
Screening for Generalized Anxiety or Panic Disorder
Table 3. Performance Characteristics of Self-report Instruments
Instrument
No. (%
Prevalence)a
Study
Age, Mean
(SD), y
(95% CI)
Females, %
Sensitivity
Specificity
LR+
LR–
Quality
Rating
GAD
GAD-7
Spitzer et al,23 2006
965 (7.6)
47 (16)
65
0.89
(0.82-0.96)
0.83
(0.80-0.85)
5.1
(4.3-6.0)
0.13
(0.07-0.26)
I
GAD-Q-IV
Moore et al,25 2014
99 (27)
39 (13)
85
0.89
(0.77-1.0)
0.63
(0.51-0.74)
2.4
(1.7-3.3)
0.18
(0.1-0.5)
III
88 (15)
73
64
0.39
(0.12-0.65)
0.88
(0.81-0.95)
3.2
(1.3-8.0)
0.70
(0.45-1.08)
III
20
ADS-GA
Krasucki et al,
SDDS-PC
Leon et al,21 1996
1999
501 (16)
49 (13)
66
0.74
(0.64-0.83)
0.82
(0.78-0.86)
4.1
(3.2-5.2)
0.32
(0.22-0.46)
I
18
Broadhead et al,
1995
257 (5.4)
40 (13)
79
0.92
(0.76-1.00)
0.54
(0.49-0.59)
2.0
(1.6-2.4)
0.15
(0.02-1.01)
I
Broadhead et al,18
1995
388 (3.1)
39 (12)
73
0.86
(0.67-1.00)
0.60
(0.53-0.66)
2.1
(1.6-2.8)
0.24
(0.07-0.87)
I
0.78
(0.66-0.87)
0.67
(0.47-0.82)
2.6
(1.6-4.1)
0.31
(0.22-0.43)
Summary SDDS-PC
Panic Disorder
PHQ
Spitzer et al,22 1999
585 (6.0)
46 (17)
66
0.81
(0.68-0.93)
0.99
(0.98-1.00)
78
(29-210)
0.20
(0.11-0.37)
SDDS-PC
Leon et al,21 1996
501 (8.0)
49 (13)
66
0.70
(0.56-0.84)
0.91
(0.88-0.93)
7.9
(5.5-11)
0.33
(0.20-0.53)
Broadhead et al,18
1995
257 (6.2)
40 (13)
79
0.78
(0.62-0.94)
0.80
(0.76-0.84)
3.9
(2.9-5.2)
0.28
(0.14-0.56)
I
Broadhead et al,18
1995
388 (7.0)
39 (12)
73
0.63
(0.39-0.86)
0.83
(0.78- 0.88)
3.8
(2.3-6.0)
0.45
(0.23-0.70)
I
0.71
(0.60-0.80)
0.86
(0.77-0.91)
4.9
(3.0-7.9)
0.35
(0.25-0.48)
Summary SDDS-PC
10-Item scale
BPDS
Barsky et al,16 1997
19
Johnson et al,
2007
I
124 (26)
47
57
0.72
(0.56-0.88)
0.71
(0.60-0.80)
2.4
(1.7-3.6)
0.40
(0.22-0.70)
II
295 (14)
54 (11)
66
0.61
(0.46-0.76)
0.29
(0.23-0.35)
0.86
(0.66-1.1)
1.36
(0.88-2.08)
I
56 (23)
49 (16)
73
0.85
(0.65-1.00)
0.81
(0.67-0.92)
4.6
(2.3-8.9)
0.19
(0.05-0.68)
III
431 (18)
55 (16)
60
0.93
(0.88-0.99)
0.53
(0.48-0.58)
2.0
(1.8-2.3)
0.12
(0.05-0.29)
I
GAD or Panic Disorder
BAI-PC
Beck et al,17 1997
PRIME-MD
Spitzer et al,24 1994
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 of Mental Disorders; SDDS-PC, Symptom Driven Diagnostic
System for Primary Care.
All studies were conducted in primary care with unselected participants, except
that by Barsky et al,16 which was conducted at a specialty clinic and selected
patients presenting with heart palpitations.
yielded similar diagnostic accuracy results across the sex distribution of the studies we evaluated (range female, 64% to 85%).
includes a brief depression module previously found to have high
sensitivity and specificity for diagnosing depression.28
The 4 instruments had high heterogeneity for the LR+ (I2, 92%;
P < .001), but the LR− showed low heterogeneity (I2, 14%; P = .32).
In a meta-regression, age was not associated with the summary LR+
(R2, 0), suggesting that the results are similar in the age range we
evaluated (mean age range 39 to 54 years). The meta-regression
showed that the summary LR+ accounted for a small amount of the
variability in the LR+ (R2, 15%; P = .03).
Panic Disorder
We assessed the heterogeneity of 4 of the 6 studies for identifying
patients with panic disorder. One study16 was not included because it assessed patients with palpitations who presented to specialists rather than unselected patients presenting to a primary care
provider. A second study19 was not included because it had no diagnostic utility (both LR CIs included 1), so it could not classify the
presence or absence of panic disorder.
The Patient Health Questionnaire (PHQ), using a positive response to all 5 questions, had good sensitivity (81%) and specificity
(99%), the best LR+ (78; 95% CI, 29-210), and the best LR− (0.20;
95% CI, 0.11-0.37). The PHQ requires less than 1 minute for completion and has an easy literacy level. The SDDS-PC is also efficient, with
a summary LR+ of 4.9 (95% CI, 3.0-7.9) and summary LR− of 0.35
(95% CI, 0.25-0.48). An additional advantage of the PHQ is that it
82
a
Reported Ns were calculated according to the number of patients who
completed the criterion standard and not the number enrolled in the study;
age is reported as mean (standard deviation).
Combined Screening for GAD and Panic Disorder
For identifying patients who may have either GAD or panic disorder,
the Beck Anxiety Inventory–Primary Care performed well compared
with other instruments, with an LR+ of 4.6 (95% CI, 2.3-8.9) and an
LR− of 0.19 (95% CI, 0.05-0.68). The instrument has an easy literacy
and can be completed quickly (approximately 1 minute). An alternative combined instrument, the Primary Care Evaluation of Mental Disorders, has the fewest number of questions for the patient (3), short
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Screening for Generalized Anxiety or Panic Disorder
completion time (1 minute), and easy literacy level. At a threshold score
of less than or equal to 1 question with a positive response, individuals with no positive responses have the lowest LR− with the narrowest CI for either anxiety disorder (LR−, 0.12; 95% CI, 0.05-0.29).
Discussion
We found that 2 screening instruments, GAD-7 for GAD and the PHQ
for panic disorder, have good performance characteristics and are
feasible for use in primary care. Further validation of these instruments is needed because neither instrument was replicated in more
than 1 primary care population.
Study Strengths
This study was a highly structured and systematic review of the extant evidence. Our evidence synthesis was guided by a carefully designed standardized protocol, including a systematic search of research databases and relevant bibliographies, double data
abstraction, and use of validated criteria to assess the quality of identified studies. Our multidisciplinary team included expertise in internal medicine, primary care, psychiatry, and psychology. Our search
identified a large number of anxiety screening instruments, but few
had been studied in primary care populations. These instruments
had moderate to good operating characteristics, but unlike instruments used in the detection of other common mental illnesses such
as depression or dementia, the operating characteristics have not
been replicated in multiple samples. Even for the SDDS-PC—the only
instrument evaluated in multiple studies—the versions studied were
different, which might change the test performance.
Study Limitations
In most studies, threshold values for the screening instrument were
specified after analysis of results instead of before. Thus, replication
is needed to validate the cutoffs recommended in these studies. Additionally, many of the studies did not confirm the diagnosis with the
referencestandardinallpatients,orinarandomsampleofthem,which
could introduce partial verification bias. A further limitation is the lack
of studies reporting on patient outcomes and societal influence. This
lack of important patient outcomes has been recognized as a challenge in systematic reviews of diagnostic tests.29 Because our eligibility criteria were designed to exclude poor-quality studies (ie, studies
in which the same person conducted the screening and criterion standard), we may have excluded studies that could provide low-level evidence on the topic. Furthermore, one of the better-performing measures, the Beck Anxiety Inventory–Primary Care, was tested in a very
small sample (n = 56) and that study17 was rated as having a higher risk
of bias (quality rating = III). A solution to these issues is to encourage
future high-quality validation studies, which are notably absent despite that many of them were published almost 20 years ago. The criterion standard for GAD and panic disorder has not changed appreciably in that time, and thus the performance characteristics of these
measures remain applicable to current diagnoses. Finally, these studies were not designed to address differing performance in subgroups, so our evaluation of age and sex as explanations for varying
performance is based on a small number of studies, uses indirect comparisons, and should be considered exploratory. Indeed, future studies would benefit from the inclusion of older patients (>65 years) and
The Rational Clinical Examination Clinical Review & Education
moreethnicallydiversesamplestobetterdeterminehowthesescreening measures perform in different subgroups.
How to Learn a Method for Diagnosing GAD
and Panic Disorder
Both the GAD-7 and PHQ screening instruments are available online (www.phqscreeners.com) and have been translated into many
languages. Because both of these instruments are selfadministered, minimal clinician training is needed to administer them.
Additional advantages of GAD-7 are that it has good operating characteristics in a 2-item abbreviated version (the GAD-2) and in screening for anxiety disorders other than GAD.4 A manual for scoring both
instruments is also available online. All of the instruments included
in this review are for screening or case-finding purposes and do not
diagnose GAD or panic disorder. Although these instruments may
be used as part of the initial diagnostic evaluation, a criterionbased diagnosis must be established through further evaluation by
a primary care physician or by a mental health professional to whom
the patient is referred. Such confirmation should be determined by
follow-up questions based on the DSM-5 (outlined in Table 1) and
should rule out psychiatric disorders with related symptoms (eg,
posttraumatic stress disorder, depression) and medical causes of
symptoms suggestive of anxiety. The studies we reviewed used DSMIII or DSM-IV diagnostic criteria for GAD and panic disorder; no significant changes in these criteria were introduced in DSM-5.
Treatment
Screening alone is not sufficient to ensure that patients with anxiety disorders in the primary care setting receive appropriate treatment. Although referring a patient for a psychiatric evaluation is one
option, primary care physicians should also familiarize themselves
with the diagnostic criteria for GAD and panic disorder, as well as with
pharmacologic and other treatments for these disorders that are appropriate for primary care. Collaborative care models integrating psychiatric treatment in the primary care setting have also been shown
to be effective for anxiety disorders.7 Furthermore, because there
is symptom overlap between GAD or panic disorder and other psychiatric diagnoses, false-positive results on any of these screening
instruments may be not only “true” false-positives (ie, when the patient meets the criteria for no related diagnoses) but also due to the
presence of a related psychiatric disorder. As such, a positive screening result, even if it is a false-positive for GAD or panic disorder, may
indicate the need for further evaluation of the patient.
Scenario Resolution
You observe that Ms B has important risk factors for an anxiety disorder, and her trip to urgent care suggests a possible panic attack.
You decide that in addition to checking her blood pressure, you will
conduct case-finding for GAD and panic disorders. You administer
the GAD-7 and PHQ, wherein she scores 12 on the GAD-7 and answers no to the PHQ item about anxiety attacks. With a pretest probability of 20% for GAD (based on an estimate of twice the prevalence in unselected primary care patients) and a GAD-7 LR+ of 5.1,
Ms B. has a 59% probability of having GAD. After discussing options for evaluation and treatment, you refer her for a psychiatric
evaluation in which her condition may be diagnosed and treated with
empirically supported treatments such as cognitive behavioral
therapy or an appropriate pharmacotherapy.
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83
Clinical Review & Education The Rational Clinical Examination
Bottom Line
There are several promising case-finding instruments with good
performance characteristics for GAD and panic disorder in primary 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 of the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Williams, Benjamin,
McDuffie.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: Herr, Benjamin, McDuffie.
Critical revision of the manuscript for important
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 of Potential Conflicts of 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 of 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 of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Disclaimer: The findings and conclusions in this
article are those of the authors, who are responsible
for its contents; the findings and conclusions do not
necessarily represent the views of the Department
of Veterans Affairs or the US government.
Therefore, no statement in this article should be
construed as an official position of the Department
of Veterans 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 of the
manuscript. We also thank Liz Wing, MA, Megan
von Isenburg, MS, and Avishek Nagi, MS, for
assistance with manuscript preparation and
literature searching. No one received financial
compensation for his/her contributions.
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