Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic

Survey on Alcohol and Related Conditions

BRIDGET F. GRANT 1*, DEBORAH S. HASIN 2 , FREDERICK S. STINSON 1 , DEBORAH A. DAWSON 1 , W. JUNE RUAN1 , RISË B. GOLDSTEIN1 ,

SHARON M. SMITH 1 , TULSHI D. SAHA1 A N D BOJI HUANG1

1 Laboratory of Epidemiology and Biometry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA; 2 Departments of Epidemiology and Psychiatry,

Columbia University and New York State Psychiatric Institute, NY, USA

ABSTRACT

Background. This study addressed the prevalences, correlates, co-morbidity and disability of DSM- IV generalized anxiety disorder (GAD) and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The study pre- sents nationally representative data, for the first time, on prevalence, correlates, co-morbidity, and comparative disability of DSM-IV GAD.

Method. Data are taken from a large (n=43093) representative sample of the adult USA popu- lation.

Results. Prevalences of 12-month and lifetime GAD were 2.1% and 4.1%. Being female, middle- aged, widowed/separated/divorced, and low income increased risk, while being Asian, Hispanic, or Black decreased risk. GAD was highly co-morbid with substance use, and other anxiety, mood, and personality disorders. Co-morbidity in GAD was not substantially greater than for most other Axis I and II disorders. Disability and impairment in pure GAD were equivalent to pure mood disorders, but significantly greater than in pure substance use, and other anxiety and personality disorders. Individuals co-morbid for GAD and each mood disorder were more disabled than those with pure forms of GAD or each mood disorder. When co-morbid with GAD, nicotine dependence and other anxiety and personality disorders were not associated with increased disability over that associated with pure GAD, but GAD did show increased disability over that due to each of these disorders in pure form.

Conclusions. Associations between GAD and Axis I and II disorders were strong and significant, with variation among specific disorders. Results strongly support GAD as an independent disorder with significant impairment and disability.

INTRODUCTION

Generalized anxiety disorder (GAD) is a chronic, disabling disorder associated with sub- stantial personal, societal, and economic costs (Ballenger et al. 2001; Wittchen, 2002). Individuals with GAD more frequently utilize

* Address for correspondence: Dr Bridget F. Grant, Laboratory of Epidemiology, Room 3077, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, M.S. 9304, 5635 Fishers Lane, Bethesda, MD 20892-9304, USA. (Email: [email protected]) The views and opinions expressed in this report are those of the

authors and should not be construed to represent the views of any of the sponsoring agencies or the USA government.

Psychological Medicine, 2005, 35, 1747–1759. f 2005 Cambridge University Press doi:10.1017/S0033291705006069 Printed in the United Kingdom

1747

primary and specialty health care resources than the mental health sector (Ormel et al. 1994; Schonfeld et al. 1997). GAD is highly associated with other psychiatric disorders, and this co- morbidity increases the economic and personal burden and severity of the disorder (Kessler et al. 1994; Wittchen et al. 1994, 2002; Judd et al. 1998; Stein, 2001; Nutt et al. 2002).

The concept and diagnostic criteria of GAD have changed significantly since the disorder first appeared in the Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-III) (APA, 1980). Despite these changes, rates of GAD have remained relatively consist- ent throughout the subsequent revised third edition (DSM-III-R; APA, 1987) and fourth edition (DSM-IV; APA, 1994) classifications in epidemiological surveys conducted worldwide since the early 1980s (Lee et al. 1987; Wittchen et al. 1992; Merikangas et al. 1996; Bijl et al. 1998; Meyer et al. 2000; Carter et al. 2001; Kringlen et al. 2001; Wittchen & Hoyer, 2001; Andrade et al. 2002; Hunt et al. 2002; Alonso et al. 2004; Faravelli et al. 2004a, b; Jacobi et al. 2004; Kawakami et al. 2004; Vincente et al. 2004; Kessler et al. 2005a, b).

For DSM-III, lifetime rates of GAD were 3.6–9.5% (mean 5.4; median 4.0%). Two ad- ditional surveys (Wells et al. 1989; Stefansson et al. 1991) based on DSM-III criteria found extremely high rates of lifetime GAD (21.7% and 31.1%), findings that remain to be ex- plained. For DSM-III-R, lifetime rates of GAD were 1.4–5.4% (mean 3.5%; median 3.4%). For DSM-IV, lifetime rates were 0.8–6.4% (mean 4.0%; median 4.3%). Twelve-month prevalences of GAD were similar for DSM-III (2.4–2.8%: mean 3.0%; median 2.6%), DSM- III-R(0.8–3.1%:mean2.0%;median1.8%)and DSM-IV(0.5–3.7%:mean2.4%;median3.1%).

High rates of co-morbidity found among GAD patients (Roy-Byrne, 1996; Noyes & Hoehn-Saric, 1998; Noyes, 2001) have raised concerns about GAD as an independent dis- order, with suggestions that GAD might be better conceptualized as a prodrome, residual, or severity marker of other disorders (Breslau & Davis, 1985; Noyes et al. 1992). A central nosological issue arising from this debate is whether generalized anxiety is itself associated with impairment or disability, or whether the impairment in individuals with GAD is due

entirely to other co-morbid disorders. The co- morbidity of GAD with major depressive epi- sode (MDE) has been of special interest because of the high level of co-morbidity and the status of MDE as one of the most burdensome dis- orders worldwide (Murray & Lopez, 1996).

Epidemiological studies have addressed this question by assessing the comparative disability of GAD and MDE. In these studies (Kessler et al. 1999, 2002; Kessler, 2000) the separate and joint effects of GAD and MDE were evaluated by comparing the disability of pure GAD, pure MDE, and the two conditions when co-morbid. No significant differences in disability were found between pure GAD and pure MDE, and two of the three surveys found that individuals with co-morbid GAD-MDE had significantly greater disability than those with either pure GAD or pure MDE.

These findings have led researchers to con- clude that the status of GAD as an independent disorder is at least as strongly supported as it is for MDE. However, to better understand GAD, current and detailed information is needed about its prevalence and its disability relative to a broader array of anxiety, mood, substance use, and personality disorders (PDs) than ex- amined in earlier studies. Representative general population data are also needed to supplement clinical studies of GAD. Accordingly, this study addressed the prevalences, correlates, co- morbidity and disability of DSM-IV GAD and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (Grant et al. 2003a, 2004a). The sample size (n=43093) and excellent response rate (81%) of the NESARC allow for the accurate estimation of rates of GAD in minorities not previously studied on a national basis and the co-morbidity and comparative disability of GAD and specific psychiatric conditions not previously assessed in nationally representative samples.

METHOD

Sample

The 2001–2002 NESARC is a representative sample of the USA conducted by NIAAA, as

1748 B. F. Grant et al.

described elsewhere (Grant et al. 2003a, 2004a). The NESARC target population was the civ- ilian population residing in households and group quarters, 18 years and older. Face-to-face interviews were conducted with 43093 re- spondents at their residences. Eighty-one per cent of all randomly selected respondents com- pleted the 1-hour interviews. Blacks, Hispanics, and young adults (aged 18–24 years) were oversampled, with data adjusted for this over- sampling and household- and person-level non- response. The weighted data were then adjusted to represent the USA civilian population based on the 2000 Census.

DSM-IV diagnostic interview

The diagnostic interview was the NIAAA Alcohol Use Disorder and Associated Dis- abilities Interview Schedule – DSM-IV version (AUDADIS-IV) (Grant et al. 2001). This diag- nostic interview, designed for lay interviewers, was developed to advance measurement of substance use and mental disorders in large- scale surveys.

DSM-IV GAD

DSM-IV GAD was diagnosed when excessive anxiety and worry were present more days than not for at least 6 months, about a number of events or activities, accompanied by difficulty controlling the worry and at least three of the six DSM-IV GAD symptoms. Lifetime GAD was defined as having at least one episode of GAD over the life course. Respondents with an epi- sode of GAD in the year preceding the interview were classified as having 12-month GAD. Diagnoses of GAD also required that the DSM- IV clinical significance criterion be met, that is, symptoms of the disorder must have caused clinically significant distress or impairment.

Other psychiatric disorders

Like GAD, other anxiety (panic disorder with and without agoraphobia, social phobia, and specific phobia) and mood [major depressive disorder (MDD), dysthymia, bipolar I, bipolar II] diagnoses in this report are DSM-IV primary diagnoses. In DSM-IV, ‘primary’ excludes mental disorders that are substance-induced or due to a medical condition. All mood and other anxiety disorders satisfied the DSM-IV clinical

significance criterion and MDD diagnoses also ruled out bereavement.

AUDADIS-IV questions operationalize DSM-IV criteria for alcohol and drug-specific abuse and dependence for 10 drug classes (Grant et al. 2004a) (aggregated in this report). Consistent with DSM-IV, lifetime diagnoses of alcohol abuse required at least one of the four criteria for abuse either in the 12-month period preceding the interview or previously. Alcohol dependence diagnoses required at least three of the seven DSM-IV criteria for dependence dur- ing the past year. For prior diagnoses of alcohol dependence, at least three criteria must have occurred within a 1-year period. Drug use dis- order and nicotine dependence (Compton et al. 2004; Grant et al. 2004b, c) diagnoses used the same algorithms.

AUDADIS-IV assessments of DSM-IV PDs have been described in detail previously (Grant et al. 2004d). These include avoidant, depen- dent, obsessive-compulsive, paranoid, schizoid, histrionic and antisocial personality disorders. DSM-IV PD diagnoses require evaluating long- term patterns of functioning. AUDADIS-IV PD diagnoses were made accordingly. Respon- dents needed to endorse the required number of DSM-IV symptom items for the specific PD, with at least one symptom causing distress or social/occupational dysfunction.

As reported in detail elsewhere (Chatterji et al. 1997; Cottler et al. 1997; Pull et al. 1997; Vrasti et al. 1997; Canino et al. 1999; Grant et al. 1995, 2003b, 2004a; Nelson et al. 1999; Hasin et al. 2003) test–retest reliability was fair for GAD (kappa=0.42) and reliability (kappa >0.74) and validity were good to excellent for sub- stance use disorders. Reliability was fair to good for mood and other anxiety disorders (kappa 0.40–0.60) and personality disorders (kappa 0.40–0.67). In addition, evidence bearing on the validity of GAD diagnoses was ascertained using the Mental Component, Social Func- tioning, Role Emotional Functioning, and Mental Health scales of the Short Form-12v2, a reliable and valid measure of disability used in population surveys (Ware et al. 2002). Each SF-12v2 disability scale is a norm-based score with a mean of 50 and standardized range of 0–100. Higher scores indicate less disability. Linear regression analyses of associations be- tween GAD and SF-12v2 scores controlling for

Generalized anxiety disorder in the USA 1749

sociodemographic characteristics and other psychiatric disorders showed highly significant relationships (p<0.00001) between each mental disability scale and GAD. With few exceptions, analyses show similar relationships between other DSM-IV anxiety, mood, and personality disorders (Grant et al. 2004a, c–e; Hasin et al. 2005) and SF-12v2 scales.

Other measures

Treatment utilization, age at onset, age at first treatment, number of episodes, and duration of only or longest (if applicable) episode were as- certained among respondents with lifetime GAD. Respondents were classified as receiving treatment for GAD if they: (1) visited a coun- selor, therapist, doctor, or psychologist; (2) were a patient in a hospital for at least one night; (3) visited an emergency room; or (4) were prescribed medications.

Statistical analyses

Weighted percentages, means, and medians were computed to derive prevalences and clini- cal correlates of GAD. Logistic regression analyses yielded odds ratios (ORs), indicating rough measures of association, between: (1) 12- month GAD and sociodemographic correlates; and (2) 12-month and lifetime GAD and other disorders, adjusted for sociodemographic fac- tors. Linear regression analyses were then used to estimate the associations of GAD and each other anxiety, mood, and substance use dis- order, and PDs at 12 months with measures of impairment derived from the four mental dis- ability scales of the SF-12v2. Linear regression analyses compared disability: (1) between pure GAD and each other pure disorder; (2) between pure GAD and GAD co-morbid with each other disorder to assess the effect on disability of the other disorder over and above GAD; and (3) between each pure psychiatric disorder and GAD co-morbid with each other psychiatric disorder in order to assess the effect on disability of GAD over and above that of each psychiatric disorder. All three comparisons were assessed in a single multivariate linear regression model, one for each psychiatric disorder being con- trasted with GAD. All models controlled for other DSM-IV disorders as well as socio- demographic characteristics. Standard errors

for all analyses were estimated using SUDAAN (Research Triangle Institute, 2004) a software package that adjusts for design characteristics of the survey.

RESULTS

Prevalence and sociodemographic correlates

Lifetime and 12-month estimates of DSM-IV GAD were 4.1% and 2.1% (Table 1). Females showed significantly greater odds than males. Odds of GAD were significantly lower among Asian, Hispanic, and Black adults compared with Whites. Compared with the oldest age group, the odds of GAD were significantly greater for middle-aged adults (30- to 64-year- olds). Odds of GAD were also significantly greater among widowed/separated/divorced respondents than among those married/co- habiting and among the three lowest income groups (<$69999) relative to the highest income group.

Onset, course, and treatment

Mean and median ages at onset of GAD were 32.7 and 30.6. Respondents with lifetime GAD reported a mean of 3.4 episodes, with mean and median durations of 11.1 and 11.6 months for the longest (or only) episode. Nearly 50% of those with GAD reported treatment specifically for the disorder. Mean and median ages at first treatment were 34.7 and 32.9.

Associations between GAD and other psychiatric disorders

GAD was significantly associated at varying levels with all other disorders except alcohol abuse. ORs were generally larger for 12-month than for lifetime disorders (Table 2). GAD was more strongly related to dependence than abuse for alcohol and drug disorders, with strongest associations for drug dependence. Mood and anxiety disorders were also strongly related to GAD. However, considerable variability in the odds ratios by specific mood and anxiety dis- orders illustrates the importance of examining the disorders separately. In both time-frames, bipolar I and dysthymia were the mood dis- orders most strongly related to GAD. Panic disorder with agoraphobia was the anxiety disorder most highly associated with GAD,

1750 B. F. Grant et al.

followed in magnitude by social phobia, specific phobia, and panic disorder without agora- phobia. With respect to PDs, dependent, avoidant, paranoid and schizoid PDs were more strongly related to GAD than other PDs.

Percentages of pure and co-morbid GAD and other psychiatric disorders

Only 10.2% of respondents with 12-month GAD did not have a current co-morbid dis- order, a figure comparable with other severe disorders including drug use disorders, bipolar I, and panic disorder with agoraphobia (Table 3). PDs rarely occurred in pure form

(6.1–12.8%), with the exception of antisocial (17.9%) and obsessive-compulsive (29.9%) PDs. Alcohol use disorders, nicotine depen- dence, and specific phobia were associated with the greatest percentages (36.9–40.5%) of pure disorders.

Pure GAD versus other pure psychiatric disorders

Table 4 presents the linear regression coefficients comparing disability as measured on the four SF-12v2 mental disability scales between 12- month pure GAD (i.e. the referent group) and each of the other pure 12-month psychiatric

Table 1. Prevalence of 12-month and lifetime DSM-IV generalized anxiety disorder and odds ratios of lifetime generalized anxiety disorder by sociodemographic characteristics

Characteristic

12-month (n=894) Lifetime (n=1757)

% (S.E.) % (S.E.) OR (95% CI)

Total 2.1 (0.10) 4.1 (0.17)

Sex Male 1.3 (0.11) 2.8 (0.18) 0.5 (0.45–0.59) Female 2.8 (0.15) 5.4 (0.23) 1.0

Race-ethnicity White 2.2 (0.12) 4.6 (0.20) 1.0 Black 1.9 (0.22) 3.0 (0.26) 0.6 (0.53–0.78) Native American 2.6 (0.63) 6.3 (1.07) 1.4 (0.96–2.00) Asian 1.1 (0.29) 1.9 (0.44) 0.4 (0.26–0.65) Hispanic 1.7 (0.24) 2.8 (0.28) 0.6 (0.47–0.73)

Age (yr) 18–29 2.1 (0.20) 3.2 (0.28) 1.2 (0.98–1.57) 30–44 2.5 (0.19) 4.6 (0.26) 1.8 (1.47–2.21) 45–64 2.1 (0.15) 5.2 (0.27) 2.1 (1.71–2.48) 65+ 1.0 (0.12) 2.6 (0.22) 1.0

Marital status Married/cohabiting 1.7 (0.11) 3.7 (0.19) 1.0 Widowed/separated/divorced 3.3 (0.22) 6.8 (0.34) 1.9 (1.68–2.13) Never married 2.0 (0.18) 3.3 (0.21) 0.9 (0.75–1.04)

Education Less than high school 2.3 (0.23) 3.7 (0.30) 0.9 (0.73–1.05) High school 2.3 (0.18) 4.3 (0.26) 1.0 (0.88–1.19) College or higher 1.9 (0.12) 4.2 (0.21) 1.0

Income $0–$19999 2.6 (0.17) 4.6 (0.24) 1.6 (1.19–2.13) $20000–$34999 1.9 (0.17) 3.9 (0.25) 1.3 (1.01–1.79) $35000–$69999 1.5 (0.14) 3.9 (0.28) 1.3 (1.01–1.79) $70000+ 1.0 (0.20) 2.9 (0.36) 1.0

Urbanicity Urban 2.0 (0.12) 4.0 (0.19) 1.0 Rural 2.4 (0.20) 4.6 (0.28) 0.9 (0.75–1.04)

Region Northwest 1.8 (0.20) 3.5 (0.35) 0.8 (0.58–1.02) Midwest 2.4 (0.26) 5.0 (0.40) 1.1 (0.86–1.44) South 2.0 (0.16) 3.7 (0.24) 0.8 (0.64–1.02) West 2.1 (0.20) 4.5 (0.42) 1.0

S.E., Standard error; OR, odds ratio; CI, confidence interval.

Generalized anxiety disorder in the USA 1751

disorders. Coefficients that are both positive and significant indicate that respondents with the other pure disorder have significantly lower disability than those with pure GAD (or, alternatively, respondents with pure GAD have significantly greater disability than those with other pure psychiatric disorders). Coefficients that are not statistically significant indicate that there are no differences in disability between the pure GAD and the other pure psychiatric dis- orders.

With few exceptions, respondents with pure GAD have significantly greater disability than respondents with pure alcohol or drug use dis- orders, pure nicotine dependence, each other

pure anxiety and personality disorder. In con- trast, respondents with pure GAD were no more or less disabled than those with each pure mood disorder.

Disability of pure GAD and other psychiatric disorders relative to co-morbid disorders

Results in the first four columns of Table 5 in- dicate the disability of GAD when co-morbid compared to the disability associated with pure GAD, the reference group. Each column shows a different subscale of the disability measure.

There were no significant increases in dis- ability of GAD when co-morbid with alcohol, drug use, other anxiety, or personality disorders compared with the disability associated with pure GAD (columns 1–4). However, disability was significantly greater when GAD was co- morbid with mood disorders compared with the disability associated with pure GAD.

Columns 5 through 8 indicate the disability of GAD when co-morbid compared with the dis- ability associated with other psychiatric dis- orders when pure (the other disorders served as reference groups in these columns). Disability was not increased when GAD was co-morbid with alcohol or drug use disorders compared with the disability associated with these dis- orders when pure. However, disability was sig- nificantly increased when GAD was co-morbid with other disorders compared with the dis- ability associated with these disorders when pure, including nicotine dependence, and mood, anxiety, and PDs.

DISCUSSION

Prevalences of 12-month and lifetime DSM-IV GAD in this general population survey were 2.1% and 4.1%. The 12-month and lifetime rates were within the ranges (0.5–3.7%; 0.8–6.4%) and corresponded closely to the mean estimates (2.0% and 4.0%) of DSM-IV GAD found in previous referenced epidemi- ologic surveys. These prevalences are slightly lower than those found in the NCS-Replication (Kessler et al. 2005a, b) largely because cases of substance-induced GAD were not excluded and the DSM-IV clinical significance criteria were not applied in that survey. Further, 12-month episodes of GAD in the NCS-R were defined by

Table 2. Twelve-month and lifetime odds ratios (ORs) of DSM-IV generalized anxiety disorder and other psychiatric disorders

Other psychiatric disorder

12-month adjusted* Lifetime adjusted

OR (95% CI) OR (95% CI)

Any alcohol use disorder 2.0 (1.54–2.63) 2.2 (1.89–2.51) Alcohol abuse 1.0 (0.64–1.49) 1.1 (0.95–1.32) Alcohol dependence 3.1 (2.24–4.22) 2.8 (2.46–3.24)

Any drug use disorder 4.5 (3.19–6.40) 2.7 (2.35–3.17) Any drug abuse 2.0 (1.16–3.35) 1.6 (1.30–1.91) Any drug dependence 9.8 (5.84–16.49) 5.2 (4.18–6.58)

Nicotine dependence 2.9 (2.34–3.52) 2.5 (2.15–2.88)

Any mood disorder 18.7 (15.77–22.15) 14.1 (12.20–16.31) Major depressive disorder

8.6 (7.12–10.45) 5.7 (5.00–6.50)

Dysthymia 12.4 (9.33–16.35) 7.1 (5.92–8.64) Bipolar I 13.6 (10.64–17.36) 8.8 (7.43–10.48) Bipolar II 5.1 (3.26–7.83) 5.0 (3.54–7.03)

Any anxiety disorder 8.9 (7.39–10.63) 7.5 (6.53–8.50) Panic disorder 12.9 (10.24–16.37) 7.3 (6.25–8.41) Panic disorder with agoraphobia

19.3 (13.62–27.36) 13.3 (10.09–17.53)

Panic disorder without agoraphobia

8.7 (6.48–11.77) 4.8 (4.00–5.68)

Social phobia 10.7 (8.49–13.50) 8.4 (7.13–9.81) Specific phobia 6.0 (5.08–7.20) 5.4 (4.68–6.14)

Any personality disorder 9.1 (7.69–10.83) 7.2 (6.31–8.32) Avoidant 11.3 (8.77–14.44) 10.7 (8.72–13.15) Dependent 13.5 (8.57–21.25) 13.1 (8.36–20.50) Obsessive-compulsive 6.2 (5.09–7.44) 5.3 (4.58–6.24) Paranoid 9.4 (7.57–11.63) 8.9 (7.55–10.56) Schizoid 7.6 (6.00–9.67) 7.1 (5.83–8.72) Histrionic 5.9 (4.30–8.21) 5.9 (4.58–7.62) Antisocial 4.6 (3.58–6.01) 4.1 (3.29–5.00)

OR, Odds ratio; CI, confidence interval. Generalized anxiety disorder and sociodemographic variables

served as independent variables with each other psychiatric disorder serving as the dependent variable. * Adjusted for age, race-ethnicity, sex, marital status, education,

income, urbanicity, region of country.

1752 B. F. Grant et al.

durations of 1 month or more rather than 6 months or more as specified by the DSM-IV.

GAD was more common among women, consistent with most epidemiologic surveys conducted since the early 1980s. Due to its size, the NESARC provides more precise infor- mation on race-ethnic differences than any other source. One previous study found no difference in the odds of GAD among Blacks, Hispanics and Whites (Wittchen et al. 1994) while another found higher rates among Blacks (Blazer et al. 1991) for lifetime GAD. The NESARC findings of lower odds among Asians, Blacks and Hispanics contribute new information. How- ever, the finding of lower rates among disad- vantaged minority groups does not rule out potential disparities in the treatment for GAD among minorities, an important topic for further investigation.

Consistent with previous surveys, the odds of GAD were significantly greater among widowed/ separated/divorced individuals and those with lower socioeconomic status (Wells et al. 1989;

Stefansson et al. 1991; Wittchen et al. 1994). Earlier surveys were inconsistent on age groups at highest risk for GAD. Due to its large sample size, NESARC results indicating that the ‘baby boom’ birth cohort is at highest risk are likely to be accurate. Further investigation to better understand the factors leading to this important finding should shed light on environmental risks for GAD.

Contrasting with earlier surveys showing age at onset of GAD in late adolescence or early twenties (Barlow et al. 1986; Burke et al. 1991; Kendler et al. 1992; Rogers et al. 1999; Kessler et al. 2001) NESARC found an average age of onset of GAD of 32.7, similar to the onsets associated with MDD (30.4 years), and panic disorder with (28.0) and without (31.8) agoraphobia (Hasin et al. 2005). In contrast to previous surveys (Angst & Vollrath, 1991; Blazer et al. 1991) and clinical studies (Mancuso et al. 1993; Noyes et al. 1996; Yonkers et al. 1996, 2000) showing that GAD episodes com- monly persist for a decade or longer, the average

Table 3. Number, percentages and rates of 12-month DSM-IV pure and co-morbid generalized anxiety disorder and other psychiatric disorders

Psychiatric disorder

Pure disorder Co-morbid disorder

na %b Rate na %b Rate

Substance use disorder Any alcohol use disorder 1353 40.1 3.4 1974 59.9 5.1 Any drug use disorder 106 14.0 0.3 671 86.0 1.7 Nicotine dependence 2048 40.5 5.2 2914 59.5 7.6

Mood disorder Major depressive disorder 709 28.6 1.5 1625 71.4 3.8 Dysthymia 105 16.0 0.2 489 84.0 1.1 Bipolar I 109 11.4 0.2 774 88.6 1.8 Bipolar II 75 19.2 0.2 281 80.8 0.7

Other anxiety disorder Generalized anxiety 87 10.2 0.2 807 89.8 1.9 Panic with agoraphobia 17 7.1 0.1 237 92.9 0.5 Panic without agoraphobia 142 20.6 0.3 511 79.4 1.2 Social phobia 200 17.8 0.5 940 82.2 2.3 Specific phobia 1218 36.9 2.6 1855 63.1 4.5

Personality disorderc

Avoidant 83 7.2 0.2 912 92.8 2.2 Dependent 11 6.1 0.1 197 93.9 0.5 Obsessive-compulsive 958 29.9 2.4 2303 70.1 5.5 Paranoid 260 10.2 0.5 1845 89.8 4.0 Schizoid 192 12.8 0.4 1233 87.2 2.7 Histrionic 68 8.2 0.2 740 91.8 1.7 Antisocial 272 17.9 0.7 1150 82.1 3.0

a Numbers based on unweighted figures. b Percentages based on weighted figures.

c Personality disorders assessed only on lifetime basis.

Generalized anxiety disorder in the USA 1753

duration of a GAD episode in the NESARC was 11.1 months and the average number of episodes was 3.4. GAD is probably more chronic among patients than others because these are likely to be the most severe cases. Further, the Epidemiologic Catchment Area Survey (Blazer et al. 1991) finding of an average duration of 6.4 years is based on the age at onset of the first symptom of GAD and not the age at onset of the full syndrome as defined here.

The NESARC indicated a continued lack of treatment for many individuals with GAD. Nearly 50% of individuals with GAD received no treatment, with an average 2-year lag be- tween onset and first treatment. The suffering and social/economic burden of this disorder is avoidable through highly effective pharmaco- logical and psychological treatments (Arikian & Gorman, 2001; Culpepper, 2002; Gorman, 2002). That the proportion of treated cases has remained virtually unchanged over the past two decades (Blazer et al. 1991; Wittchen et al. 1994)

suggests that efforts remain to be made to de- liver effective treatments for GAD to the many who still need them and that such treatment should be delivered sooner.

The results provide new, detailed information on the co-morbidity of DSM-IV GAD and substance abuse and dependence. Most previous studies did not include samples large enough to investigate linkages between specific substance use disorders and mental disorders. Results presented above show that GAD is strongly as- sociated with alcohol, drug and nicotine depen- dence, but not abuse, a finding consistent with the few surveys that have assessed these dis- orders (Wittchen et al. 1994; Kessler et al. 1996; Carter et al. 2001; Hunt et al. 2002; Alonso et al. 2004). Further, GAD showed a stronger re- lationship to drug dependence than to alcohol and nicotine dependence, a difference that re- mains to be explained.

GAD was also strongly associated with mood and other anxiety disorders. For 12-month dis- orders the magnitude ranged from ORs of 19.3

Table 4. Linear regression analyses of DSM-IV pure generalized anxiety disorder and pure other psychiatric disorders predicting disabilitya

Other psychiatric disorder

Mental Disability Scale

b (95% CI)

Social Functioning Scale

b (95% CI)

Role Emotional Functioning Scale

b (95% CI)

Mental Health Scale

b (95% CI)

Substance use disorder Any alcohol use disorder 8.4 (5.8–11.0)* 7.0 (3.8–10.2)* 10.4 (5.0–15.8)** 5.9 (2.7–9.1)** Any drug use disorder 5.3 (1.3–9.2)** 3.8 (x0.4–8.0)**** 5.9 (0.9–11.0)**** 3.2 (x1.2–7.6) Nicotine dependence 7.6 (5.1–10.1)* 5.5 (2.3–8.7)** 8.5 (3.7–13.4)** 5.0 (2.1–8.0)**

Mood disorder Major depressive disorder 1.2 (x1.6–4.0) 1.3 (x2.1–4.7) 3.4 (x0.9–7.8) x0.9 (x4.4–2.6) Dysthymia 0.9 (x2.4–4.1) x1.0 (x4.9–2.9) x0.3 (x5.3–4.7) x1.0 (x4.6–2.6) Bipolar I 0.6 (x3.2–4.4) x3.2 (x7.4–0.9) 4.3 (x1.6–10.1) x3.3 (x7.5–0.9) Bipolar II 3.6 (x0.5–7.6) 1.4 (x3.6–6.4) 6.4 (0.6–12.2)**** 1.1 (x3.2–5.4)

Other anxiety disorder Panic with agoraphobia 4.8 (1.7–11.2)**** 4.1 (x2.0–10.2) 4.3 (2.3–10.9)**** 2.7 (x3.8–9.2) Panic without agoraphobia 5.6 (2.3–9.0)** 4.3 (0.2–8.3)**** 4.9 (0.1–9.8)**** 2.5 (x0.6–5.6) Social phobia 7.8 (5.0–10.6)* 6.8 (3.4–10.2)* 9.6 (5.3–13.9)* 5.6 (2.5–8.6)** Specific phobia 8.9 (6.4–11.5)* 6.6 (3.3–9.9)* 9.7 (5.1–14.4)* 6.3 (3.3–9.2)**

Personality disorderb

Avoidant 4.3 (0.9–7.7)**** 3.2 (x1.2–7.7) 5.9 (0.3–11.4)**** 2.2 (x1.7–6.1) Dependent 4.8 (x0.4–9.9)**** 0.5 (x10.6–11.6) x4.7 (x15.5–6.0) 5.6 (0.2–11.0)**** Obsessive-compulsive 8.0 (5.4–10.6)* 5.7 (2.3–9.1)** 9.0 (4.5–13.6)* 5.3 (2.3–8.4)** Paranoid 8.1 (5.1–11.0)* 5.4 (1.4–9.3)*** 9.0 (3.0–15.1)** 5.2 (1.2–9.3)*** Schizoid 9.1 (6.1–12.1)* 6.0 (2.5–9.5)** 10.0 (5.2–14.7)* 7.0 (3.3–10.8)** Histrionic 6.5 (2.3–10.7)** 4.8 (x0.2–9.7)**** 6.9 (2.2–11.6)** 4.4 (0.4–8.3)**** Antisocial 7.5 (4.2–10.8)* 4.4 (0.3–8.5)**** 8.1 (3.2–12.9)** 5.1 (1.3–9.0)***

CI, confidence interval. a Referent category was pure generalized anxiety disorder. Each model controlled for age, race-ethnicity, sex, marital status, education,

income, urbanicity, region of the country, and all other psychiatric disorders. b Personality disorders assessed only on lifetime basis. * p<0.0001, ** p<0.005, *** p<0.01, **** p<0.05.

1754 B. F. Grant et al.

Table 5. Comparative disability of pure generalized anxiety disorder (GAD), each pure other psychiatric disorder and co-morbid GAD and each other psychiatric disordera

Other

psychiatric

disorder

Co-morbid GAD–other psychiatric disorder

v. pure GAD (referent category)

Co-morbid GAD–other psychiatric disorder

v. pure other psychiatric disorder (referent category)

Mental

Disability

Scale (1)

Social

Functioning

Scale (2)

Role Emotional

Functioning

Scale (3)

Mental Health

Scale (4)

Mental Disability

Scale (5)

Social

Functioning

Scale (6)

Role Emotional

Functioning

Scale (7)

Mental Health

Scale (8)

b (95% CI) b (95% CI) b (95% CI) b (95% CI) b (95% CI) b (95% CI) b (95% CI) b (95% CI)

Substance use

disorder

Any alcohol

use disorder

2.7 (x3.8–9.3) 5.5 (0.0–11.0) 8.0 (0.5–15.6) 0.9 (x7.0–8.9) x5.7 (x11.6–0.3) x1.5 (x6.1–3.0) x2.4 (x7.7–3.0) x5.0 (x12.2–2.3)

Any drug

use disorder

4.3 (x6.7–15.2) x4.1 (x17.2–8.9) 4.7 (x7.9–17.3) x1.7 (x10.1–6.6) x1.0 (x11.8–9.8) x7.9 (x20.1–4.2) x1.2 (x12.8–10.4) x4.9 (x13.0–3.2)

Nicotine

dependence

1.4 (x3.4–6.3) x1.9 (x7.6–3.8) 3.3 (x3.3–9.9) x3.0 (x8.1–2.2) x6.2 (x10.3 to x2.1)** x7.4 (x11.7 to x3.1)** x5.2 (x9.6 to x0.8)**** x8.0 (x12.2 to x3.8)**

Mood disorder

Major

depressive

disorder

x6.7 (x11.0 to x2.5)**x3.7 (x8.7–1.3)**** x1.8 (x7.0–3.3) x7.6 (x12.1 to x3.0)** x8.0 (x11.2 to x4.7)* x5.0 (x8.5 to x1.5)** x5.3 (x8.4 to x2.1)** x6.7 (x9.7 to x3.6)*

Dysthymia x7.9 (x13.4 to x2.3)**x4.7 (x10.2–0.9)**** x4.1 (x10.7–2.6) x8.7 (x14.5 to x2.9)** x8.8 (x14.0 to x3.5)** x3.7 (x8.8–1.4) x3.8 (x9.2–1.6) x7.7 (x13.2 to x2.2)*** Bipolar I x8.0 (x12.5 to x3.5) x7.1 (x13.0 to x1.2)**** x4.5 (x10.8–1.7) x11.0 (x15.3 to x6.8)* x8.6 (13.0 to x4.2)** x3.9 (x9.6–1.8) x8.8 (x13.7 to x3.8)** x7.7 (x11.8 to x3.7)** Bipolar II x6.8 (x14.2–0.7)**** x2.4 (x11.8–7.0) x2.0 (x10.3–6.3) x5.1 (x12.7–2.5) x10.3 (x17.4 to x3.2)** x3.8 (x12.8–5.2) x8.4 (x16.0 to x0.8)**** x6.2 (x13.5–1.2)

Other anxiety

disorder

Panic with

agoraphobia

7.0 (x2.4–16.1) 9.1 (x0.5–18.6) 5.7 (x3.3–14.6) 2.2 (x6.5–10.8) 2.3 (x8.0–12.5) 5.0 (x4.8–14.8) 1.4 (x7.6–10.3) x0.5 (x11.0–10.0)

Panic without

agoraphobia

x1.1 (x6.8–4.6) 2.7 (x3.3–8.7) 4.1 (x2.6–10.8) x4.3 (x10.0–1.4) x6.8 (x12.3–1.2)**** x1.6 (x7.2–4.1) x0.8 (x6.4–4.8) x6.8 (x12.3 to x1.3)****

Social phobia x0.3 (x5.8–5.2) x0.2 (x6.8–6.5) 1.6 (x5.4–8.5) 0.3 (x5.7–6.4) x8.1 (x13.1 to x3.1)** x7.0 (x13.3 to x0.7)**** x8.1 (x14.1 to x2.0)*** x5.2 (x10.5–0.1)**** Specific phobia 6.0 (2.1–9.8)** 5.3 (0.7–10.0) 6.3 (0.5–12.0)**** 2.0 (x1.9–5.8) x3.0 (x5.9 to x0.1)**** x1.3 (x4.5–2.0) x3.5 (x7.3–0.3)**** x4.3 (x7.0 to x1.6)

Personality

disorderb

Avoidant x2.9 (x8.4–2.7) 2.9 (x3.9–9.8) x0.4 (x8.7–7.9) x6.8 (x12.7 to x0.9) x0.3 (x6.3–5.8) x6.3 (x13.2 to x0.5)**** x9.0 (x14.3 to x3.6)** x17.3 (x31.3 to x3.4)** Dependent x12.6 (x26.9–1.7) x5.9 (x20.8–9.1) x18.3 (x37.1–0.5) x16.4 (x29.9 to x2.8) x17.3 (x31.3 to x3.4)**** x6.3 (x22.8–10.2) x13.6 (x33.2–6.0)** x22.0 (x35.5 to x8.5)** Obsessive-

compulsive

1.4 (x3.2–6.0) x0.4 (x6.0–5.3) 2.6 (x3.7–8.9) x1.1 (x5.9–3.6) x6.6 (x10.5 to x2.8)** x6.0 (x10.7 to x1.4)**** x6.4 (x10.8 to x2.0)** x6.5 (x10.3 to x2.6)**

Paranoid 0.5 (x4.3–5.3) 0.5 (x5.6–6.6) 3.5 (x2.8–9.8) x2.5 (x7.8–2.9) x7.5 (x12.1 to x3.0)** x4.9 (x10.2–0.5)**** x5.5 (x10.5 to x0.6)**** x7.7 (x12.7 to x2.7)** Schizoid x0.3 (x5.3–4.8) 2.1 (x3.2–7.4) 2.8 (x3.6–9.1) x3.5 (x8.9–2.0) x9.4 (x14.0 to x4.8)* x3.9 (x8.7–1.0) x7.2 (x12.8 to x1.5)**** x10.5 (x15.8 to x5.2)** Histrionic 5.9 (x1.1–12.9) 10.4 (0.5–20.2)**** 4.1 (x3.4–11.6) 1.1 (x6.4–8.5) x0.6 (x7.8–6.7) 5.6 (x4.0–15.2) x2.8 (x9.8–4.2) x3.3 (x11.3–4.8) Antisocial x3.4 (x10.1–3.3) x6.2 (x14.7–2.3) x4.2 (x13.0–4.6) x7.1 (x13.7 to x0.5)* x10.9 (x16.4 to x5.3)* x10.6 (x18.1 to x3.0)** x12.3 (x20.1 to x4.4)** x12.3 (x17.8 to x6.7)*

a Each model controlled for age, race-ethnicity, sex, marital status, education, income, urbanicity, region of the country and all other psychiatric disorders.

b Personality disorders assessed only on lifetime basis. * p<0.0001, ** p<0.005, *** p<0.01, **** p<0.05.

G en era

lized a n x iety

d iso

rd er

in th e U S A

1 7 5 5

for panic disorder with agoraphobia to 6.0 for specific phobia. With regard to mood disorders, bipolar I and dysthymia were more strongly re- lated to GAD than MDD and bipolar II, a new finding obscured in previous surveys that as- sessed only manic episodes and major depressive episodes (as opposed to MDD and bipolar dis- orders). Information in this report can provide a starting point for investigations of these ob- served patterns of co-morbidity.

Information on personality disorders among USA adults was not previously available and is highly relevant to GAD, as indicated by clinical studies (Mavissakalian et al. 1993; Reich et al. 1994; Sanderson et al. 1994; Dyke et al. 2001). All PDs assessed had strong associations with GAD, but magnitudes varied. The Cluster B PDs (histrionic, antisocial) showed lowest asso- ciations with GAD. Cluster A PDs (paranoid, schizoid) showed intermediate associations. Cluster C PDs (avoidant, dependent) showed the strongest associations with GAD, except for obsessive-compulsive PD. Future studies will address these varying associations and their impact on GAD, questions that will be ad- dressed when the remaining PDs assessed in Wave 2 are included.

An important goal of this study was to com- pare disability among pure cases of GAD, pure cases of other disorders and co-morbid cases. Consistent with previous epidemiologic re- search, impairment of pure GAD was equiva- lent to pure MDD (Kessler, 2000; Kessler et al. 1999, 2002) as well as other mood disorders (i.e. bipolar I, bipolar II and dysthymia). More cru- cial were the new findings that pure GAD is significantly more disabling than pure alcohol and drug use disorders, nicotine dependence, other anxiety disorders and PDs, even when sociodemographic and all other co-occurring disorders were controlled. However, disability associated with other anxiety disorders, PDs and especially substance use disorders may dif- fer from that of GAD, suggesting that future research should be extended to other domains of disability not presented here.

Consistent with most previous studies on GAD and MDE (Kessler, 2000; Kessler et al. 2002) individuals with co-morbid GAD-MDD were more disabled than those with pure GAD or pure MDD and individuals with GAD were more disabled than those without GAD. This

was also the case for other mood disorders. However, when co-morbid with GAD, nicotine dependence, and other anxiety and PDs were not associated with increased disability com- pared with disability associated with pure GAD. In contrast, GAD showed increased disability over that due to each of these disorders in pure form. The results for alcohol and drug use disorders were unique in that individuals co-morbid for GAD and alcohol or drug use disorders were no more disabled than those with pure GAD or pure alcohol or drug use dis- orders. It is possible that alcohol and drugs are being used to self-medicate the anxiety asso- ciated with GAD. If this were the case, and self-medication were successful, the greater dis- ability associated with GAD would be reduced, resulting in no significant differences in dis- ability between individuals who were co-morbid for these disorders and those with pure GAD and pure alcohol or drug use disorders. This is precisely what this study demonstrated.

Taken together, these results argue against the view that GAD is a prodromal or residual form of other psychiatric disorders. GAD is no more co-morbid than many other psychiatric disorders assessed in this study and disability and role impairment in GAD is comparable to that due to mood disorders and significantly greater than impairment due to nicotine depen- dence, other anxiety disorders and PDs. Thus, there was no more evidence to support with- holding independent status for GAD than for many other disorders.

With regard to public health implications, this study has determined the magnitude of GAD confronting the nation and identified im- portant subgroups of the population at risk for the disorder, information critical to the plan- ning of local and national health services. With respect to economic implications, individuals with GAD are heavy users of primary care and specialty health care resources, contributing substantially to the non-psychiatric burden as- sociated with anxiety disorders in the USA (Ormel et al. 1994; Ustun & Sartorius, 1995; Schonfeld et al. 1997; Wittchen, 2002). Despite high levels of help-seeking among individuals with GAD, most present with physical health complaints that are often one focus of their an- xiety, rather than with anxiety as the source of concern in itself. Health care initiatives geared

1756 B. F. Grant et al.

towards increasing recognition and treatment of GAD among individuals with the disorder and among primary care and specialty care physi- cians can lead to a reduction in the economic burden of GAD and improve the quality of life of those afflicted with a disorder as disabling as other psychiatric disorders. Moreover, as the results of this study demonstrate, individuals with co-morbid GAD and mood disorders were more disabled than those with pure GAD or each pure mood disorder, suggesting that in- creased intervention efforts be targeted toward these more-impaired co-morbid subgroups of GAD.

With regard to clinical implications, the re- sults of this study are clear in showing that substance use, other anxiety, mood and per- sonality disorders are highly co-morbid with GAD. Comprehensive evaluation of patients with GAD should include a systematic assess- ment of these and other co-morbid disorders. Longitudinal epidemiologic and clinical studies that attempt to address the limitations of this cross-sectional survey promise to elucidate the risk of chronicity and disability in GAD con- ferred by additional conditions and increase our understanding of patterns of co-morbidity. The second of three planned waves of the NESARC will allow use of the Wave 1 GAD results as a platform for investigation of these important prospective questions.

ACKNOWLEDGMENTS

The National Epidemiologic Survey on Alcohol and Related Conditions was funded by the National Institute on Alcohol Abuse and Alcoholism with supplemental funding from the National Institute on Drug Abuse. Support is acknowledged from K05AA014221, R01DA018652 and the New York State Psychiatric Institute (Dr Hasin).

DECLARATION OF INTEREST

None.

REFERENCES

Alonso, J., Angermeyer, M. C., Bernert, S., Bruffaerts, R., Brugha,

T. S., Bryson, H., Girolamo, G., Graaf, R., Demyttenaere, K.,

Gasquet, I., Haro, J. M., Katz, S. J., Kessler, R. C., Kovess,

V., Lepine, J. P., Ormel, J., Polidori, G., Russo, L. J., Vilagut, G.,

Almansa, J., Arbabzadeh-Bouchez, S., Autonell, J., Bernal, M.,

Buist-Bouwman, M. A., Codony, M., Domingo-Salvany, A., Ferrer,

M., Joo, S. S., Martinez-Alonso, M., Matschinger, H., Mazzi, F.,

Morgan, Z., Morosini, P., Palacin, C., Romera, B., Taub, N. &

Vollebergh, W. A. (2004). Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatrica Scan- dinavica (Suppl.) 16, 21–27.

Andrade, L., Walters, E. E., Gentil, V. & Laurenti, R. (2002). Prevalence of ICD-10 mental disorders in a catchment area in the city of Sao Paulo, Brazil. Social Psychiatry and Psychiatric Epidemiology 37, 316–325.

Angst, J. & Vollrath, M. (1991). The natural history of anxiety disorder and generalized anxiety disorder. Acta Psychiatrica Scandinavica 141, 572–575.

APA (1980). Diagnostic and Statistical Manual of Mental Disorders (DSM-III). American Psychiatric Association: Washington, DC.

APA (1987). Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R). American Psychiatric Associ- ation: Washington, DC.

APA (1994). Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). American Psychiatric Association: Wash- ington, DC.

Arikian, S. R. & Gorman, J. M. (2001). A review of the diagnosis, pharmacologic treatment and economic aspects of anxiety dis- orders. Primary Care Companion Journal of Clinical Psychiatry 3, 110–117.

Ballenger, J. C., Davidson, J. R. T., Lecrubier, Y., Nutt, D. J.,

Borkovek, T. D., Rickels, K., Stein, D. J. & Wittchen, H.-U. (2001). Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 62, 53–58.

Barlow, D. H., Blanchard, E. B., Vermilyea, J. A., Vermilyea, B. B. &

Dinardo, P. A. (1986). Generalized anxiety and generalized anxiety disorder: description and reconceptualization. American Journal of Psychiatry 143, 40–44.

Bijl, R. V., Ravelli, A. & Zessen, G. V. (1998). Prevalence of psychi- atric disorder in the general population: results of the Netherlands Mental Health Survey and Incidence Survey (NEMESIS). Social Psychiatry and Psychiatric Epidemiology 33, 587–595.

Blazer, D. G., Hughes, D., George, L. K., Swartz, M. & Boyer, R.

(1991). Generalized anxiety disorder. In Psychiatric Disorders in America: The Epidemiologic Catchment Area Study (ed. L. N. Robins and D. A. Regier). The Free Press: New York.

Breslau, N. & Davis, G. C. (1985). Further evidence on the doubtful validity of generalized anxiety disorder. Psychiatry Research 16, 177–179.

Burke, K. C., Burke, J. D., Rae, D. S. & Regier, D. A. (1991). Comparing age at onset of major depression and other psychiatric disorders by birth cohorts in five U.S. community populations. Archives of General Psychiatry 48, 789–795.

Canino, G. J., Bravo, M., Ramfrez, R., Febo, V., Fernandez, R. &

Hasin, D. S. (1999). The Spanish Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS): re- liability and concordance with clinical diagnoses in a Hispanic population. Journal of Studies on Alcohol 60, 790–799.

Carter, R. M., Wittchen, H.-U., Pfister, H. & Kessler, R. C. (2001). One-year prevalence of subthreshold and threshold DSM-IV gen- eralized anxiety disorder in a nationally representative sample. Depression and Anxiety 13, 78–88.

Chatterji, S., Saunders, J. B., Vrasti, R., Grant, B. F., Hasin, D. &

Mager, D. (1997). Reliability of the alcohol and drug modules of the Alcohol Use Disorder and Associated Disabilities Interview Schedule – Alcohol/Drug-Revised (AUDADIS-ADR): an inter- national comparison. Drug and Alcohol Dependence 47, 171–185.

Compton, W. M., Grant, B. F., Colliver, J. D., Glantz, M. D. &

Stinson, F. S. (2004). Prevalence of marijuana use disorders in the United States: 1991–1992 and 2001–2002. Journal of the American Medical Association 291, 2114–2121.

Cottler, L. B., Grant, B. F., Blaine, J., Mavreas, V., Pull, C., Hasin,

D., Compton, W. M., Rubio-Stipec, M. & Mager, D. (1997).

Generalized anxiety disorder in the USA 1757

Concordance of DSM-IV alcohol and drug use disorder criteria and diagnoses as measured by AUDADIS-ADR, CIDI and SCAN. Drug and Alcohol Dependence 47, 195–205.

Culpepper, L. (2002). Generalized anxiety disorder in primary care: emerging issues in management and treatment. Journal of Clinical Psychiatry 63, 35–42.

Dyke, I. R., Phillips, K. A., Warshaw, M. G., Dolan, R. T., Shea, T.,

Stout, R. L., Massion, A. O., Zlotnick, C. & Keller, M. B. (2001). Patterns of personality pathology in patients with generalized anxiety disorder, panic with and without agoraphobia, and social phobia. Journal of Personality Disorders 15, 60–71.

Faravelli, C., Abrardi, L., Bartolozzi, D., Cecchi, C., Cosci, F.,

D’adamo, D., Lo Iacono, B., Ravaldi, C., Scarpato, M. A., Truglia,

E. & Rosi, S. (2004a). The Sesto Fiorentino study: background, methods and preliminary results. Lifetime prevalence of psychi- atric disorders in an Italian community sample using clinical in- terviewers. Psychotherapy and Psychosomatics 73, 216–225.

Faravelli, C., Abrardi, L., Bartolozzi, D., Cecchi, C., Cosci, F.,

D’adamo, D., Lo Iacono, B., Ravaldi, C., Scarpato, M. A., Truglia,

E., Rossi Prodi, P. M. & Rosi, S. (2004b). The Sesto Fiorentino study: point and one-year prevalences of psychiatric disorders in an Italian community sample using clinical interviewers. Psycho- therapy and Psychosomatics 73, 226–234.

Gorman, J. M. (2002). Treatment of generalized anxiety disorder. Journal of Clinical Psychiatry 63, 17–23.

Grant, B. F., Dawson, D. A. & Hasin, D. S. (2001). The Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. National Institute on Alcohol Abuse and Alcoholism: Bethesda, MD.

Grant, B. F., Dawson, D. A., Stinson, F. S., Chou, P. S., Kay, W. &

Pickering, R. (2003b). The Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV): reliability of alcohol consumption, tobacco use, family history of depression and psychiatric diagnostic modules in a general population sam- ple. Drug and Alcohol Dependence 71, 7–16.

Grant, B. F., Dawson, D. A., Stinson, F. S., Chou, S. P. &

Pickering, R. P. (2004b). The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991–1992 and 2001–2002. Drug and Alcohol Dependence 74, 223–234.

Grant, B. F., Harford, T. C., Dawson, D. A., Chou, P. S. & Pickering,

R. P. (1995). The Alcohol Use Disorder and Associated Disabilities Interview schedule (AUDADIS): reliability of alcohol and drug modules in a general population sample. Drug and Alcohol Dependence 39, 37–44.

Grant, B. F., Hasin, D. S., Chou, S. P., Stinson, F. S. & Dawson,

D. A. (2004c). Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Archives of General Psychiatry 61, 1107–1115.

Grant, B. F., Hasin, D. S., Stinson, F. S., Dawson, D. A., Chou, S. P.,

Ruan, W. J. & Pickering, R. P. (2004d). Prevalence, correlates, and disability of personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Journal of Clinical Psychiatry 65, 948–958.

Grant, B. F., Moore, T. C., Shepard, J. & Kaplan, K. (2003a). Source and Accuracy Statement, Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). National Institute on Alcohol Abuse and Alcoholism: Bethesda, MD.

Grant, B. F., Stinson, F. S., Dawson, D. A., Chou, S. P.,

Dufour, M. C., Compton, W., Pickering, R. P. & Kaplan, K.

(2004a). Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of General Psychiatry 61, 807–816.

Grant, B. F., Stinson, F. S., Hasin, D. S., Dawson, D. A., Chou, S. P.

& Anderson, K. (2004e). Immigration and lifetime prevalence of DSM-IV psychiatric disorders among Mexican Americans and non-Hispanic whites in the United States: results from the National Epidemiologic Survey on Alcohol and Related Con- ditions. Archives of General Psychiatry 61, 1226–1233.

Hasin, D. S., Goodwin, R. D., Stinson, F. S. & Grant, B. F. (2005). The epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Con- ditions. Archives of General Psychiatry 62, 54–60.

Hasin, D. S., Schuckit, M. A., Martin, C. S., Grant, B. F., Bucholz,

K. K. & Helzer, J. E. (2003). The validity of DSM-IV alcohol de- pendence: what do we know and what do we need to know? Alcoholism, Clinical and Experimental Research 27, 244–252.

Hunt, C., Issakidis, C. & Andrews, G. (2002). DSM-IV generalized anxiety disorder in the Australian National Survey of Mental Health and Well-Being. Psychological Medicine 32, 649–659.

Jacobi, F., Wittchen, H.-U., Holting, C., Hofler, M., Pfister, H.,

Muller, N. & Lieb, R. (2004). Prevalence, co-morbidity and corre- lates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychological Medicine 34, 597–611.

Judd, L. L., Kessler, R. C., Paulus, M. P., Zeller, P. V., Wittchen,

H.-U. & Kunovac, J. L. (1998). Comorbidity as a fundamental feature of generalized anxiety disorder: results from the National Comorbidity Survey. Acta Psychiatrica Scandinavica 98, 6–11.

Kawakami, N., Shimizu, H., Haratani, T., Iwata, N. & Kitamura, T.

(2004). Lifetime and 6-month prevalence on DSM-III-R psychi- atric disorders in an urban community in Japan. Psychiatry Research 121, 291–301.

Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C. & Eaves,

L. J. (1992). Generalized anxiety disorder in women: a popu- lation-based twin study. Archives of General Psychiatry 49, 267– 272.

Kessler, R. C. (2000). The epidemiology of pure and co-morbid gen- eralized anxiety disorder: a review and evaluation of recent re- search. Acta Psychiatrica Scandinavica 102, 7–13.

Kessler, R. C., Berglund, P. A., Demler, O., Jin, R. & Walters, E. E.

(2005a). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593–602.

Kessler, R. C., Berglund, P. A., Dewit, D. J., Ustun, T. B., Wang,

P. S. & Wittchen, H.-U. (2002). Distinguishing generalized anxiety disorder from major depression: prevalence and impairment from current pure and co-morbid disorders in the U.S. and Ontario. International Journal of Methods in Psychiatric Research 11, 99–111.

Kessler, R. C., Chiu, W. T., Demler, O. & Walters, E. E. (2005b). Prevalence, severity, and co-morbidity of 12-month DSM-IV dis- orders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 617–627.

Kessler, R. C., Dupont, R. L., Berglund, P. A. & Wittchen, H.-U.

(1999). Impairment in pure and co-morbid generalized anxiety disorder and major depression at 12 months in two national sur- veys. American Journal of Psychiatry 156, 1915–1923.

Kessler, R. C., Keller, M. B. & Wittchen, H.-U. (2001). The epi- demiology of generalized anxiety disorder. Psychiatric Clinics of North America 24, 19–39.

Kessler, R. C., Mcgonagle, K. A., Zhao, S., Nelson, C. B., Hughes,

M., Eshleman, S. & Kendler, K. S. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Archives of General Psychiatry 51, 8–19.

Kessler, R. C., Nelson, C. B., Mcgonagle, K. A., Edlund, M. J., Frank,

R. G. & Leaf, P. J. (1996). The epidemiology of co-occurring ad- dictive and mental disorders: implications for prevention and ser- vice utilization. American Journal of Orthopsychiatry 66, 17–31.

Kringlen, E., Torgersen, S. & Cramer, B. (2001). A Norwegian psy- chiatric epidemiological study. American Journal of Psychiatry 158, 1091–1098.

Lee, C. K., Kawk, Y. S., Rhee, H., Kim, Y. S., Han, J. H., Choi, J. O.

& Lee, Y. H. (1987). The nationwide epidemiological study of mental disorders in Korea. Journal of Korean Medical Science 2, 19–34.

Mancuso, D. M., Townsend, M. H. & Mercante, D. E. (1993). Long- term follow-up of generalized anxiety disorder. Comprehensive Psychiatry 34, 441–446.

1758 B. F. Grant et al.

Mavissakalian, M. R., Hamann, M. S., Abou Haidar, S. & De Groot,

C. M. (1993). DSM-III personality disorders in generalized anxi- ety, panic/agoraphobia and obsessive-compulsive disorders. Comprehensive Psychiatry 34, 243–248.

Merikangas, K. R., Angst, J., Eaton, W. W., Canino, G. J., Rubio-

Stipec, M., Wacker, H., Wittchen, H.-U., Andrade, L., Essau,

C. A., Whitaker, A., Kraemer, H., Robins, L. N. & Kupfer, D. J.

(1996). Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse: results of an international task force. British Journal of Psychiatry 168, 58–67.

Meyer, C., Rumpf, H.-J., Hapke, U., Dilling, U. & John, U. (2000). Lebenszeitprevalenz psychischer sterunger in der erwachsenen Allgemein-bevolkerung: prgebnisse der TACOS studie. Nerven- arzt, 71, 535–542.

Murray, C. J. & Lopez, A. D. (1996). The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. Harvard University Press: Cambridge, MA.

Nelson, C. B., Rehm, J., Ustun, B., Grant, B. F. & Chatterji, S. (1999). Factor structure of DSM-IV substance disorder criteria endorsed by alcohol, cannabis, cocaine and opiate users: results from the World Health Organization Reliability and Validity Study. Addiction 94, 843–855.

Noyes, R. (2001). Comorbidity in generalized anxiety disorder. Psychiatric Clinics of North America 24, 41–55.

Noyes, R. & Hoehn-Saric, R. (1998). Generalized anxiety disorder. In The Anxiety Disorders (ed. R. Noyes and R. Hoehn-Saric). Cambridge University Press: London.

Noyes, R., Holt, C. S. & Woodman, C. L. (1996). Natural course of anxiety disorders. In Long-term Treatments of Anxiety Disorders (ed. M. R. Mavissakalian and R. F. Prien). American Psychiatric Press: Washington, DC.

Noyes, R., Woodman, C., Garvey, M. J., Cook, B. L., Suelzer, M.,

Clancy, J. & Anderson, D. J. (1992). Generalized anxiety disorder vs. panic disorder: distinguishing characteristics and patterns of co-morbidity. Journal of Nervous and Mental Disease 180, 369– 379.

Nutt, D. J., Ballenger, J. C., Sheehan, D. & Wittchen, H.-U. (2002). Generalized anxiety disorder: co-morbidity, comparative biology and treatment. International Journal of Neuropsychopharmacology 5, 315–325.

Ormel, J., Vonkorff, M., Ustun, T. B., Pini, S., Korten, A. &

Oldehinkel, T. (1994). Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. Journal of the American Medical Association 272, 1741–1748.

Pull, C. B., Saunders, J. B., Mavreas, V., Cottler, L. B., Grant, B. F.,

Hasin, D. S., Blaine, J., Mager, D. & Ustun, B. T. (1997). Concordance between ICD-10 alcohol and drug use disorder cri- teria and diagnoses as measured by the AUDADIS-ADR, CIDI and SCAN: results of a cross-national study. Drug and Alcohol Dependence 47, 207–216.

Reich, J. H., Perry, C., Shera, D., Dyke, I. R., Vasile, R., Goisman,

R. M., Rodriguez-Villa, F., Massion, A. O. & Keller, M. B. (1994). Comparison of personality disorders in different anxiety disorder diagnoses: panic, agoraphobia, generalized anxiety and social phobia. Annals of Clinical Psychiatry 6, 125–134.

Research Triangle Institute (2004). Software for Survey Data Analysis (sudaan) Version 9.0. Research Triangle Institute: Research Triangle Park, NC.

Rogers, M. P., Warshaw, M. G., Goisman, R. M., Goldenberg, I.,

Rodriguez-Villa, F., Mallya, G., Freeman, S. A. & Keller, M. B.

(1999). Comparing primary and secondary generalized anxiety disorder in a long-term naturalistic study of anxiety disorders. Depression and Anxiety 10, 1–7.

Roy-Byrne, P. P. (1996). Generalized anxiety and mixed anxiety-de- pression: association with disability and health care utilization. Journal of Clinical Psychiatry 57, 86–91.

Sanderson, W. C., Wetzler, S., Beck, A. T. & Betz, F. (1994). Prevalence of personality disorders among patients with anxiety disorders. Psychiatry Research 51, 167–174.

Schonfeld, W. H., Verboncoeur, C. S., Fifer, S. K., Lipschutz, R. C.,

Lubeck, D. P. & Buesching, D. P. (1997). The functioning and well-being of patients with unrecognized anxiety disorders and major depressive disorder. Journal of Affective Disorders 43, 27–34.

Stefanssan, J. G., Lindal, E., Bjornsson, J. K. & Guomundsdottir, A.

(1991). Lifetime prevalence of specific mental disorders among people born in Iceland in 1931. Acta Psychiatrica Scandinavica 84, 142–149.

Stein, D. J. (2001). Comorbidity in generalized anxiety disorder: impact and implications. Journal of Clinical Psychiatry 62, 29–34.

Ustun, T. B. & Sartorius, N. (eds) (1995). Mental Illness in General Health Care: An International Study. John Wiley & Sons: Chichester, NY.

Vincente, B., Kohn, R., Rioseco, P., Saldivia, S. A., Baker, C. &

Torres, S. (2004). Population prevalence of psychiatric disorders in Chile: 6-month and 1-month rates. British Journal of Psychiatry 184, 299–305.

Vrasti, R., Grant, B. F., Chatterji, S., Ustun, B. T., Mager, D.,

Olteanu, I. & Bodoi, M. (1997). The reliability of the Romanian version of the alcohol module of the WHO Alcohol Use Disorder and Associated Disabilities Interview Schedule-Alcohol/Drug- Revised (AUDADIS-ADR). European Addiction Research 4, 144– 149.

Ware, J. E., Kosinski, M., Turner-Bowker, D. M. & Gandek, B.

(2002). How to Score Version 2 of the SF-12 Health Survey. Quality Metric: Lincoln, RI.

Wells, J. E., Bushnell, J. A., Hornblow, A. R., Joyce, P. R. & Oakley-

Brown, M. A. (1989). Christchurch Psychiatric Epidemiology Study, part 1. Methodology and lifetime prevalences for specific psychiatric disorders. Australian and New Zealand Journal of Psychiatry 23, 3315–3326.

Wittchen, H.-U. (2002). Generalized anxiety disorder: prevalence, burden and cost to society. Depression and Anxiety 16, 162–171.

Wittchen, H.-U., Essau, C. A., Von Zerssen, D., Krieg, J. C. &

Zaudig, M. (1992). Lifetime and six-month prevalence of mental disorders in the Munich Follow-Up Study. European Archives of Psychiatry and Clinical Neuroscience 241, 247–258.

Wittchen, H.-U. & Hoyer, J. (2001). Generalized anxiety disorder: nature and course. Journal of Clinical Psychiatry 62, 15–19.

Wittchen, H.-U., Kessler, R. C., Beesde, K., Krause, P., Hofler, M. &

Hayer, J. (2002). Generalized anxiety and depression in primary care: prevalence, recognition and management. Journal of Clinical Psychiatry 63, 24–34.

Wittchen, H.-U., Zhao, S., Kessler, R. C. & Eaton, W. W. (1994). DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Archives of General Psychiatry 51, 355–364.

Yonkers, K. A., Dyke, I. R., Warshaw, M. G. & Keller, M. B. (2000). Factors predicting the clinical course of generalised anxiety dis- order. British Journal of Psychiatry 176, 544–549.

Yonkers, K. A., Warshaw, M. G., Massion, A. O. & Keller, M. B.

(1996). Phenomenology and course of generalized anxiety dis- order. British Journal of Psychiatry 168, 308–313.

Generalized anxiety disorder in the USA 1759

View publication statsView publication stats

https://www.researchgate.net/publication/7563421