Case Conceptualization Paper

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Nature and Course of GAD

eneralized anxiety disorder (GAD) has, until re- cently, been a relatively poorly understood disorder.

EPIDEMIOLOGY OF GAD

A number of critical clinical and research issues affect the reliability and understanding of GAD studies. Most cli- nicians and clinical epidemiologists are familiar with the clinical syndrome of generalized anxiety characterized by excessive worrying and marked symptoms of hypervigi- lance and anxiety as the essential aspects of what was for- merly labeled anxiety neurosis before the 1980s. However, confusion exists concerning the diagnostic criteria for GAD as a distinct and treatable psychiatric disorder. Indeed, few primary care physicians are aware that specific diagnostic criteria and diagnostic tools exist. Research into GAD in the past has also been complicated by the use of different definitions. The concept and diagnostic criteria of GAD have changed significantly since its formal introduction in DSM-III in 1980, several times in the subsequent revisions, and, to date, there are still differences in the understanding of GAD between Europe and the United States. These dif- ferences are predominantly due to the use of differing di- agnostic criteria: in Europe the use of the 10th International Classification of Diseases (ICD-10) prevails, whereas in the United States and in research the Diagnostic and Sta- tistical Manual of Mental Disorders (DSM) is preferred.

Historically, the study of GAD has been further hindered by methodological difficulties occurring during research. For example, few reliable assessment methods have been available until recently. Considerable developmental work during the 1990s resulted in more appropriate diagnostic modules,5 although the instruments that are in use still dif- fer in their conceptual backgrounds, which can result in variability in their findings. Some measures are polythetic,

Generalized Anxiety Disorder: Nature and Course

Hans-Ulrich Wittchen, Ph.D., and Jürgen Hoyer, Ph.D.

Generalized anxiety disorder (GAD) is a chronic and highly prevalent disorder in the adult popula- tion, yet it remains a relatively poorly understood condition. Clinicians may be familiar with the symptoms of enduring excessive worrying, anxiety, and hypervigilance that are characteristic of GAD, but may not necessarily recognize that these are usually symptoms of a distinct psychiatric dis- order. Despite changes in diagnostic criteria, estimates of prevalence for GAD are remarkably consis- tent across epidemiologic studies. Lifetime prevalence in the general population is estimated at 5% (DSM-III and/or DSM-III-R criteria), with rates as high as 10% among women aged 40 years and above, and cross-sectional rates among primary care attenders are about 8%, making GAD the most prevalent anxiety disorder in primary care. The age at onset of GAD differs from that of other anxiety disorders: prevalence rates are low in adolescents and young adults but increase substantially with age. Females are at greater risk than males, and the disorder is correlated with being unemployed or a housewife or having a chronic medical illness. GAD is frequently associated with comorbid depres- sion and other anxiety and somatoform disorders. Significant GAD-specific disability occurs even when comorbidity is not present. (J Clin Psychiatry 2001;62[suppl 11]:15–19)

G The recent increased interest in the condition has stemmed from the finding that GAD is the second most frequent dis- order in primary care after depression,1–3 the availability of reliable diagnostic criteria and instruments,4 and the devel- opment of new treatments for this condition. However, a number of concerns remain regarding the nosology of GAD as a separate psychiatric condition. Questions have been raised concerning the diagnostic validity of standard crite- ria, the prevalence in the general population, and in particu- lar, the meaning and implications of comorbid anxiety and depressive disorders frequently seen in clinical settings. Other key concerns are whether the disorder causes GAD- specific disabilities and whether the impairments are due to comorbid conditions. This review explores the nature of GAD by examining current research into its epidemiology (prevalence rates in both the general population and in pri- mary care are considered), onset, course, risk factors, and associated comorbidity and impairment.

From the Institute of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden and Max Planck Institute of Psychiatry, Munich, Germany.

Presented at the meeting “Focus on Generalized Anxiety Disorder,” held by the International Consensus Group on Depression and Anxiety, March 30–31, 2000, in Cape Town, South Africa. The Consensus Meeting was supported by an unrestricted educational grant from SmithKline Beecham Pharmaceuticals.

Reprint requests to: Professor Hans-Ulrich Wittchen, Max Planck Institute of Psychiatry, Clinical Psychology and Epidemiology Unit, Kraepelinstr.2, 80804 Munich, Germany (e-mail: [email protected]).

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Wittchen and Hoyer

for example, the Structured Clinical Interview for DSM (SCID)6 and the World Health Organization’s Composite International Diagnostic Interview (CIDI),7 both designed specifically for administration of the apportionalized DSM criteria. On the other hand, others are of a syndromal na- ture, for example, the Clinical Interview Schedule (CIS)8

and the Schedules for Clinical Assessment in Neuropsy- chiatry (SCAN),9 resulting in differing rates.

As a consequence of these issues, direct cross-study comparisons are difficult, especially when interpreting findings not based on the same diagnostic system or instrument (DSM-III-R, DSM-IV, or ICD-10 criteria). Therefore, clear epidemiologic evidence for prevalence and risk factors for GAD has, until recently, been poor.

Prevalence of GAD Despite the fact that there have been many changes

in the diagnostic criteria for GAD during recent years, re- ported lifetime prevalence estimates in the general popula- tion (Table 1) are remarkably stable, compared with the considerable variance observed with other psychiatric dis- orders, such as depression and panic disorder, over a simi- lar age span. Based on more recent studies, the most likely lifetime prevalence rates for GAD in the general popula- tion are 5% using DSM criteria and may be slightly higher when using the wider ICD-10 criteria (6.5%). Current and 12-month prevalence rates for GAD are also reported in Table 1; these estimates depend largely on the rigidity of the definition of point prevalence and are subject to more variation than lifetime prevalence estimates. The most likely current prevalence rate in the general population seems to be in the range of 2% to 3% (DSM criteria).

The National Comorbidity Survey (NCS),24 performed in a representative sample of the U.S. general population (aged 15–54 years), is the largest study to report epidemio- logic findings for GAD to date.16 Using CIDI/DSM-III-R criteria in more than 8000 respondents, a lifetime preva- lence estimate of 5.1% (3.6% in males and 6.6% in fe- males) and a 12-month prevalence rate of 3.1% (2.0% in males and 4.3% in females) were reported. The lifetime prevalence estimate is in relatively good agreement with the findings of several other large epidemiologic studies that have been conducted throughout the world in recent years (see Table 1). The 12-month prevalence rate found by the NCS should be regarded with caution, however, since the CIDI is designed to gather lifetime prevalence rates and did not assess the presence of all of the disorder’s criteria in the preceding 12 months and thus might include a high proportion of people with lifetime GAD who have only had some significant signs of the disorder during the previous month. The 12-month prevalence estimates of threshold GAD were recently found to be lower in the German National Health Interview and Examination Sur- vey, Mental Health Supplement (GHS).23 This study used the slightly stricter DSM-IV criteria (which use the addi- tional criteria of difficulty controlling the worrying and a restricted range of associated symptoms), which increase the duration criterion from 1 month to 6 months compared with DSM-III-R, to examine GAD and other disorders in a representative sample of the German population (over 7200 adults). Using a 12-month version of the Munich- CIDI,25 the 12-month prevalence rate for GAD (meeting all DSM-IV criteria) was found to be 1.5% (1.0% in men and 2.1% in women). If, however, lifetime GAD cases with still

Table 1. Prevalence of Generalized Anxiety Disorder in General Population Surveysa

Source Diagnostic Criteriab Lifetime Prevalence, % 12-Month Prevalence, % Current Prevalence, %

Weissman et al,10 United States RDC … … 2.5 Angst et al,11 Zurich, Switzerland DSM-III … 3.8 … Blazer et al,12

ECA study, Durham, NC DSM-III 6.6 3.6 1.2 ECA study, St Louis, Mo DSM-III 6.6 2.9 1.3 ECA study, Los Angeles, Calif DSM-III 4.1 2.0 1.4

Stefansson et al,13 Iceland DSM-III 21.7 … … Chen et al,14 Shatin, Hong Kong DSM-III 7.8 males … …

11.1 females Faravelli et al,15 Florence, Italy DSM-III-R 5.4 … 2.8 Wittchen et al,16 DSM-III-R 5.1 3.1 1.6 NCS, United States Offord et al,17 Ontario, Canada DSM-III-R … 1.1 … Feehan et al,18 Dunedin, New Zealand DSM-III-R … [1.8] … Canals et al,19 Spain DSM-III-R … … [0] Wittchen et al,20 Munich, Germany DSM-IV [0.8] [0.5] … Jenkins et al,21 Great Britain ICD-10 … … 6.4 Bhagwanjee et al,22 South Africa DSM-IV … … 3.7 Carter et al,23 GHS, Germany DSM-IV … 1.5 … aAdapted, with permission, from Carter et al.23 Abbreviations: DSM = Diagnostic and Statistical Manual of Mental Disorders, ECA = Epidemiologic Catchment Area, GHS = German National Health Interview and Examination Survey, ICD = International Classification of Diseases, NCS = National Comorbidity Survey, RDC = Research Diagnostic Criteria. Prevalence rates in brackets indicate that the sample comprised only adolescents. bAll studies using DSM-III used 1-month instead of 6-month criteria (as used in DSM-III-R and DSM-IV).

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Nature and Course of GAD

existing 12-month subthreshold GAD syndromes are counted as well—as was the case in the NCS study—an almost identical 12-month rate of 3.6% (2.4% in men and 4.9% in women) was confirmed. In addition, the disorder was found significantly more frequently in women than in men (odds ratio [OR] = 2.1, p < .05). The investigators also determined prevalence rates for subthreshold expressions of GAD by using different time criteria for duration, such as worrying for at least 1 month (7.8%) or worrying for at least 3 months (4.1%), and concluded that long periods of anxious worrying associated with subthreshold GAD symptoms are much more widespread in the community than threshold GAD.

When prevalence data from the NCS and GHS are ex- amined by age, it is clear that for both lifetime and 12- month prevalence rates, the lowest rates for GAD occur in the younger age groups and the highest rates are found in the older study participants (Figure 1).16,23 In the GHS,

the likelihood of receiving a diagnosis of GAD increased significantly with age (18–34 vs. 35–65 years: OR = 1.0, p < .05) when controlling for differences in gender, with point prevalence rates up to 4.4% in women aged 45 or older. These findings are consistent with the lower preva- lence rates for GAD recorded in studies of adolescents and young adults (see Table 1).

GAD, in common with panic disorder, is unique among anxiety disorders in that patients commonly present to primary care physicians for treatment.2 An international World Health Organization study used ICD-10 criteria with the CIDI to assess GAD and estimated the current preva- lence of GAD to be approximately 8% of all primary care attendees.1 A more recent reanalysis confirmed these re- sults by using more sophisticated analyses, finding a mean current prevalence rate of 7.9%.2 This study also found a wide range of prevalence rates across the participating countries, for example, 3.8% in Italy and 14.8% in Greece, possibly owing to differences in the way that countries and regions organize the provision of primary care services. It is noteworthy that this study suggests that the point preva- lence rate of GAD is considerably higher in primary care than that reported in the general population (see Table 1), suggesting that GAD patients are high utilizers of primary care resources. This is in contrast to social anxiety disor- der and most other anxiety disorders, for which the point prevalence in the general population is much higher than in primary care and subjects are unlikely to present to their family doctor owing to the nature of the condition.26

COURSE OF GAD

The presentation of GAD in primary care is similar to that of other anxiety disorders in that patients are unlikely to present directly and openly with complaints of anxiety symptoms.1 In fact, it is most likely that patients with GAD will present with somatic and sleeping problems.

The pattern of onset with GAD is different from that seen with other anxiety disorders; whereas most anxiety disorders clearly develop before the age of 20 years,27

prevalence rates for GAD in adolescents and young adults are usually low and then increase substantially with age.23

Notably in the GHS,23 few cases of full-blown DSM-IV GAD occurred before the age of 25 years. This was par- ticularly true among men. There was also a strong increase in the incidence of GAD later in life: for women, this oc- curred after the age of 35 years, whereas in men, the in- crease occurred after the age of 45 years. Furthermore, among respondents with at least 3 months of worrying, older subjects (aged 35–65 years) were more likely than younger subjects (aged 18–34 years) to have reported that their worrying had lasted for at least 6 months (OR = 3.94, p < .05). Thus, older people worry more and for longer periods of time than their younger counterparts. These findings are supported by a community study in over 3100

Figure 1. Prevalence of Generalized Anxiety Disordera

15–24

25–34

35–44

≥ 45

Total

Prevalence (%)

A g e G

ro u p (

y)

0 2 4 6 8 10 12

2 2.5

1.5 6

7.1 4.7

5.9 7.2

4.6

6.9 10.3

3.6

5.1 6.6

3.6

Total Females Males

A. Lifetime Prevalence (CIDI and DSM-III-R criteria)b

aAbbreviations: CIDI = Composite International Diagnostic Interview, DSM = Diagnostic and Statistical Manual of Mental Disorders. bData from the National Comorbidity Survey.16 cData from the German National Health Interview and Examination Survey, Mental Health Supplement.23

18–24

25–34

35–44

≥ 45

Total

Prevalence (%)

A g

e G

ro u

p (

y)

2.3 1.1

2.8 0.8

4.4 2.2

3.5 1.5

3.6 1.5

0 2 4 6 8

Including Subthreshold (DSM-III-R) Threshold (DSM-IV)

B. Twelve-Month Prevalence (Munich-CIDI and DSM-IV criteria)c

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Wittchen and Hoyer

older adults (aged 55–85 years), which found that GAD was the most frequent anxiety disorder in this elderly population (7.3%).28

Results from the GHS23 also show that the 12-month prevalence of extended worrying (worrying for at least 1 month) is lower in younger than in older participants. How- ever, worrying for long periods of time carries the same risk of developing full syndromal DSM-IV GAD irrespective of the age group.

GAD is a chronic condition in adults with a waxing and waning course. In younger patients, the course is more vari- able. Full and partial 6-month remission rates among life- time cases have shown that only one third of all patients with GAD have spontaneous remission.16

GAD is frequently associated with other psychiatric disorders. In the NCS, approximately two thirds of current (1-month) DSM-III-R GAD cases fulfilled criteria for at least one other disorder.16 GAD is frequently associated with depression or other anxiety disorders but it is only in- frequently associated with substance abuse disorders.16,23

At the same time, however, it is noteworthy that these seemingly extremely high rates of comorbidity were shown to be not remarkably different from those of other disorders, such as panic disorder and bipolar disorder.23,29

Comorbidity especially with major depressive disorder has been shown to significantly lower the probability of diagnosis and treatment of GAD and to increase disability and impairment.30 (For further discussion of comorbidity in GAD, see the article by Stein in this supplement.31)

CORRELATES AND RISK FACTORS FOR GAD

The NCS16 and GHS23 have both shown that the preva- lence of GAD increases with age and that the disorder is more common in females than in males. In addition, a number of significant correlates for GAD have been iden- tified. These include being previously married (separated, widowed, or divorced), not working, or being a house- wife.16 The NCS was also able to conclude that urbanicity, income, education, and religion lack significant associa- tion with GAD.16

Although GAD is more prevalent in women than in men and occurs more frequently in the unemployed or those that work at home than in employed people, only 16.9% of cases of GAD are found in nonworking home- makers. Even among females with GAD, the proportion of housewives does not exceed 25%.23 Therefore, GAD is not a disorder that is solely found in housewives.

BURDEN OF GAD

The NCS found that there is a considerable degree of impairment, professional help-seeking, and medication us- age to relieve symptoms in people with GAD, whether or not they had a comorbid mental disorder.16 To assess the

disability and impairment caused by pure GAD, analyses of data from studies that control for comorbid disorders, which may affect quality of life, have been implemented. Kessler and coworkers32 conducted a combined analysis of 2 U.S. general population studies (NCS16 and Midlife De- velopment in the United States Survey32) to assess whether DSM-III-R–defined GAD is itself associated with impair- ment or whether the impairment is due to comorbid depres- sion or other comorbid disorders. Assessing the proportion of patients with at least 1 day of disability/impairment in the past month, the authors showed that the impairment as- sociated with GAD alone is not only marked, but is equiva- lent in magnitude to the impairment caused by major de- pression. The highest levels of impairment were seen when GAD co-occurred with major depression.

A similar, more elaborate, recently published analysis, which included a wider range of impairment and disability measures, assessed disability in individuals with pure DSM-IV–defined GAD and GAD comorbid with major de- pression.30 The analysis used data from the GHS obtained from the Work Productivity and Activity Impairment ques- tionnaire (WPAI)33 and the 36-item short-form (SF-36).34

Impairment was defined as number of days completely lost plus number of days limited in the past month. Approxi- mately 48% of patients with comorbid GAD and major depression, 34% of those with pure GAD, and 21% of those with pure major depression had at least 6 days impaired over the past month. This study also considered disability in terms of reduction in work productivity. Approximately 11% of the respondents with GAD and no major depres- sion and 8% of those with major depression and no GAD reported a reduction of at least 50% in activity during the past month; more than 50% and 30% of those respective patients reported some reduction in activity. Thus, GAD is associated with considerable impairment even when no comorbid depression is present.

Since GAD is highly prevalent in the primary care set- ting, patients with the disorder are likely to be high users of primary care health services, both in terms of the num- ber of visits and the proportion contacting primary care providers because of problems associated with the disor- der. GAD is a disabling condition in primary care,35,36 and the associated social disability is as severe as that seen with chronic somatic diseases.2

CONCLUSION

GAD is a highly prevalent psychiatric disorder. The lifetime prevalence rate for GAD in the general population is approximately 5% using DSM-III and/or DSM-III-R criteria and possibly slightly higher (approximately 6.5%) using ICD-10 criteria. In primary care, the point preva- lence rate is approximately 8%, making GAD the most frequent anxiety disorder in primary care and the second most frequent psychiatric disorder after depression. In

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Nature and Course of GAD

common with most other anxiety disorders, GAD more of- ten affects women than men, particularly in higher age groups. Unlike other anxiety disorders, GAD rarely occurs in childhood, making it unlikely that GAD is merely a temperament variant, personality trait, or disorder.

GAD is a persistent disorder with a waxing and waning course; only one third of lifetime GAD sufferers in the community experience spontaneous full remission. In the community, GAD also has high, although not necessarily higher, rates of comorbidity with depression and other anxiety disorders compared with the rates of comorbidity found with panic disorder or bipolar disorders. Even in the absence of comorbid disorders, GAD is as disabling as de- pressive disorders in terms of reduced work productivity and social impairment and is associated with increased use of health care services. GAD is a chronic, prevalent, and impairing psychiatric disorder that requires prompt recog- nition and effective treatment.

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