Bernd Löwe

Anxiety Disorders in Primary Care: Prevalence, Impairment, Comorbidity, and Detection

Context Anxiety and depression are both common in primary care patients, but much less attention has been paid to anxiety. Contribution The authors administered a 7-item anxiety scale (Generalized Anxiety Disorder [GAD]-7) to 965 primary care patients, who also had a structured interview, to detect an anxiety disorder. Of these patients, 19.5% had at least 1 anxiety disorder. Patients with anxiety had worse functional status, more disability days, and more physician visits, but 41% were not being treated for any anxiety disorder. The GAD-7 had high sensitivity and good specificity for detecting a generalized anxiety disorder, panic disorder, social anxiety disorder, and posttraumatic stress disorder. Implications Anxiety disorders are common, underrecognized, and undertreated, but they are easy to detect with a brief questionnaire. The Editors Anxiety and depression are the 2 most common mental health problems seen in the general medical setting (15). Although increasing attention has been paid to anxiety, it still lags far behind depression in terms of research as well as clinical and public health efforts in screening, diagnosis, and treating affected individuals. This is unfortunate given the prevalence of anxiety and its substantial impact on patient functioning, work productivity, and health care costs (614). More than 30 million Americans have a lifetime history of anxiety (15), and anxiety disorders cost an estimated

The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review

42 billion dollars per year in the United States alone, counting direct and indirect costs (16). The 4 most common anxiety disorders (excluding simple phobias that seldom present clinically) are generalized anxiety disorder, panic disorder, social anxiety disorder, and posttraumatic stress disorder (PTSD) (1723). However, despite the substantial disability associated with each anxiety disorder and the availability of effective treatments, only a minority of patients (15% to 36%) with anxiety are recognized in primary care (24, 25). In our paper, we analyze results from a large primary carebased anxiety study (26) to answer several questions. First, what is the prevalence of these 4 anxiety disorders, both individually and concurrent with one another? Second, how do these disorders compare in functional impairment, health care use, and comorbid depressive and somatic symptom burden? Third, how effective is a brief anxiety measure in screening for each disorder? Compared with previous research, our study is particularly well-positioned to ascertain commonalities among anxiety diagnoses that are traditionally considered to be discrete and to determine whether a single measure can be used as a first step, common metric. This is especially salient for the busy, complex primary care setting, in which simplifying initial recognition of mental disorders may in fact make wider efforts at recognition more feasible. Methods Patient Sample The Patient Health Questionnaire (PHQ) anxiety study (26) was conducted to develop a short measure to assess generalized anxiety disorder. Patients were enrolled from a research network of 15 primary care sites (13 family practice and 2 internal medicine sites) located in 12 states and administered centrally by Clinvest, Inc., Springfield, Missouri, from November 2004 to June 2005. The Generalized Anxiety Disorder (GAD)-7 scale was developed and validated in 2149 patients. In the original study, 2982 persons were invited to participate; of these, 2740 (92%) completed the 4-page questionnaire and had no or minimal missing data (26). To minimize sampling bias, consecutive patients were approached at each site in clinic sessions until the target quota for that week was achieved. Of the 2740 participants, the first 2149 were used for development and validation of the GAD-7 scale, whereas the last 591 were used to determine the testretest reliability of the scale. Of the 2149 patients in the validation group, 1654 agreed to a telephone interview, of whom 965 were randomly selected to undergo this interview within 1 week of their clinic visit by 1 of 2 mental health professionals: a clinical psychologist (with a PhD) or a senior psychiatric social worker. Contact information was sent by fax to each interviewer, who shuffled the fax sheets received each day and then drew from the stack several participants to interview that day. The 965 interviewed patients comprise the study population for this paper, and compared with the 1184 participants who did not undergo a mental health professional interview, these were more often women (69% vs. 63%; P= 0.003) and had slightly higher GAD-7 anxiety scores (5.7 vs. 5.1; P= 0.010) but were similar in age, race, and education. Of note, we only used data from the 1184 participants not undergoing a mental health professional interview to derive the GAD-7 (26). The study was approved by the Sterling Institutional Review Board. Study Questionnaire Before seeing their physicians, patients completed a 4-page questionnaire that included the GAD-7 (Appendix Figure). This scale was shown to have good internal and testretest reliability, as well as convergent, construct, criterion, procedural, and factorial validity for the diagnosis of generalized anxiety disorder (26). Scores on the GAD-7 range from 0 to 21; scores of 5, 10, and 15 represent mild, moderate, and severe anxiety symptoms, respectively. The first 2 items of the GAD-7 represent core anxiety symptoms, and scores on this GAD-2 subscale range from 0 to 6. Appendix Figure. The Generalized Anxiety Disorder (GAD)-7 scale. The first 2 items constitute the GAD-2 subscale. GAD-7 2006 Pfizer Inc. All rights reserved. Used with permission. The study questionnaire also included questions about age, sex, education, race or ethnicity, and marital status; the Medical Outcomes Study Short Form-20 (SF-20), which measures functional status in 6 domains (27); the 10-item anxiety subscale from the Hopkins Symptom Checklist (28); the PHQ-8 depression scale (29); a 3-item version of the Social Phobia Inventory (Mini-SPIN) (30); the 5-item PHQ panic module (25); and the PHQ-15 somatic symptom scale (31). Also, single-item global assessments of anxiety, depression, and pain based on a scale of 0 (none) to 10 (as bad as you can imagine) were included. Finally, patients reported the number of physician visits and disability days during the previous 3 months. Structured Psychiatric Interview The 2 mental health professionals, while blinded to the results of the self-report research questionnaire, conducted structured psychiatric interviews by telephone to establish independent criteria-based diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (32). The interview consisted of the generalized anxiety disorder, social anxiety disorder, and PTSD sections of the Structured Clinical Interview for DSM-IV (SCID) (33). Reinterview by telephone was used because of its feasibility in our multisite study and its demonstrated comparability with face-to-face research interviews (3436). The 2 mental health professionals based diagnoses of generalized anxiety disorder and PTSD on the SCID interview. For generalized anxiety disorder, some questions were slightly modified to better assess each DSM-IV criterion. They based a diagnosis of social anxiety disorder on whether the patient met SCID diagnostic criteria and had a Mini-SPIN score of 8 or greater, because this improves the accuracy of social anxiety disorder diagnoses (37). They based a diagnosis of panic disorder on answering yes to all 5 questions on the PHQ panic module, a threshold that reflects DSM-IV criteria and has been validated in both clinical (25) and population-based (38) samples. Statistical Analysis We estimated sample size with respect to sensitivity of the GAD-7 scale for diagnosing the target disease (generalized anxiety disorder). We needed 60 participants with generalized anxiety disorder to ensure that the total width of the 95% CI around a sensitivity proportion of 0.80 was no greater than 0.20. Given that the estimated prevalence of generalized anxiety disorder in the primary care population was 6% (18), we needed a total of 1000 unselected primary care patients to have approximately 60 patients with generalized anxiety disorder. We determined the prevalence of each of the 4 anxiety disorders and compared them in patient demographic characteristics, functional status, psychiatric comorbidity, disability days, and physician visits. Consistent with previous work (1, 26, 29, 39), we replaced missing values in a scale with the mean value of the remaining items if 25% or fewer items were missing. If more than 25% of items were missing, the sum score was not computed and was counted as missing. The amount of missing data for any individual variable or scale score was very low (<1%). The 15 sites did not differ in missing data. In addition to descriptive statistics, we used analysis of covariance to examine associations among each anxiety disorder and the 6 SF-20 functional status scales, self-reported disability days, and physician visitscontrolling for demographic variables (sex, age, race, and educational level) and study site. We ran similar models to examine the effect of the number of anxiety disorders. In all models, patients with no anxiety disorder were the reference group. We adjusted pairwise statistical comparisons by using the Bonferroni correction. Because some dependent variables displayed a skewed (but unimodal) distribution, we also reran the models using the rank transformation of the dependent variables. We examined the operating characteristics (sensitivity, specificity, and positive likelihood ratio) for a range of cutoff scores of the GAD-7 and GAD-2 for each anxiety disorder. We conducted receiver-operating characteristic curve analyses to determine the area under the curve (AUC) for each anxiety disorder. We calculated AUCs and performed statistical comparisons (GAD-7 vs. GAD-

Validation and Standardization of the Generalized Anxiety Disorder Screener (gad-7) in the General Population

BACKGROUND Depression, anxiety and somatization are the most common mental disorders in primary care as well as medical specialty populations; each is present in at least 5-10% of patients and frequently comorbid with one another. An efficient means for measuring and monitoring all three conditions would be desirable. METHODS Evidence regarding the psychometric and pragmatic characteristics of the Patient Health Questionnaire (PHQ)-9 depression, generalized anxiety disorder (GAD)-7 anxiety and PHQ-15 somatic symptom scales are synthesized from two sources: (1) four multisite cross-sectional studies (three conducted in primary care and one in obstetric-gynecology practices) comprising 9740 patients, and (2) key studies from the literature that have studied these scales. RESULTS The PHQ-9 and its abbreviated eight-item (PHQ-8) and two-item (PHQ-2) versions have good sensitivity and specificity for detecting depressive disorders. Likewise, the GAD-7 and its abbreviated two-item (GAD-2) version have good operating characteristics for detecting generalized anxiety, panic, social anxiety and post-traumatic stress disorder. The optimal cutpoint is > or = 10 on the parent scales (PHQ-9 and GAD-7) and > or = 3 on the ultra-brief versions (PHQ-2 and GAD-2). The PHQ-15 is equal or superior to other brief measures for assessing somatic symptoms and screening for somatoform disorders. Cutpoints of 5, 10 and 15 represent mild, moderate and severe symptom levels on all three scales. Sensitivity to change is well-established for the PHQ-9 and emerging albeit not yet definitive for the GAD-7 and PHQ-15. CONCLUSIONS The PHQ-9, GAD-7 and PHQ-15 are brief well-validated measures for detecting and monitoring depression, anxiety and somatization.

Monitoring Depression Treatment Outcomes With the Patient Health Questionnaire-9

Background:The 7-item Generalized Anxiety Disorder Scale (GAD-7) is a practical self-report anxiety questionnaire that proved valid in primary care. However, the GAD-7 was not yet validated in the general population and thus far, normative data are not available. Objectives:To investigate reliability, construct validity, and factorial validity of the GAD-7 in the general population and to generate normative data. Research Design:Nationally representative face-to-face household survey conducted in Germany between May 5 and June 8, 2006. Subjects:Five thousand thirty subjects (53.6% female) with a mean age (SD) of 48.4 (18.0) years. Measures:The survey questionnaire included the GAD-7, the 2-item depression module from the Patient Health Questionnaire (PHQ-2), the Rosenberg Self-Esteem Scale, and demographic characteristics. Results:Confirmatory factor analyses substantiated the 1-dimensional structure of the GAD-7 and its factorial invariance for gender and age. Internal consistency was identical across all subgroups (α = 0.89). Intercorrelations with the PHQ-2 and the Rosenberg Self-Esteem Scale were r = 0.64 (P < 0.001) and r = −0.43 (P < 0.001), respectively. As expected, women had significantly higher mean (SD) GAD-7 anxiety scores compared with men [3.2 (3.5) vs. 2.7 (3.2); P < 0.001]. Normative data for the GAD-7 were generated for both genders and different age levels. Approximately 5% of subjects had GAD-7 scores of 10 or greater, and 1% had GAD-7 scores of 15 or greater. Conclusions:Evidence supports reliability and validity of the GAD-7 as a measure of anxiety in the general population. The normative data provided in this study can be used to compare a subjects GAD-7 score with those determined from a general population reference group.

An ultra-brief screening scale for anxiety and depression: the PHQ-4.

Background:Although effective treatment of depressed patients requires regular follow-up contacts and symptom monitoring, an efficient method for assessing treatment outcome is lacking. We investigated responsiveness to treatment, reproducibility, and minimal clinically important difference of the Patient Health Questionnaire-9 (PHQ-9), a standard instrument for diagnosing depression in primary care. Methods:This study included 434 intervention subjects from the IMPACT study, a multisite treatment trial of late-life depression (63% female, mean age 71 years). Changes in PHQ-9 scores over the course of time were evaluated with respect to change scores of the SCL-20 depression scale as well as 2 independent structured diagnostic interviews for depression during a 6-month period. Test-retest reliability and minimal clinically important difference were assessed in 2 subgroups of patients who completed the PHQ-9 twice exactly 7 days apart. Results:The PHQ-9 responsiveness as measured by effect size was significantly greater than the SCL-20 at 3 months (−1.3 versus −0.9) and equivalent at 6 months (−1.3 versus −1.2). With respect to structured diagnostic interviews, both the PHQ-9 and the SCL-20 change scores accurately discriminated patients with persistent major depression, partial remission, and full remission. Test-retest reliability of the PHQ-9 was excellent, and its minimal clinically important difference for individual change, estimated as 2 standard errors of measurement, was 5 points on the 0 to 27 point PHQ-9 scale. Conclusions:Well-validated as a diagnostic measure, the PHQ-9 has now proven to be a responsive and reliable measure of depression treatment outcomes. Its responsiveness to treatment coupled with its brevity makes the PHQ-9 an attractive tool for gauging response to treatment in individual patient care as well as in clinical research.

A 4-item measure of depression and anxiety: Validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population

BACKGROUND The most common mental disorders in both outpatient settings and the general population are depression and anxiety, which frequently coexist. Both of these disorders are associated with considerable disability. OBJECTIVE When the disorders co-occur, the disability is even greater. Authors sought to test an ultra-brief screening tool for both. METHOD Validated two-item ultra-brief screeners for depression and anxiety were combined to constitute the Patient Health Questionnaire for Depression and Anxiety (the PHQ-4). Data were analyzed from 2,149 patients drawn from 15 primary-care clinics in the United States. RESULTS Factor analysis confirmed two discrete factors (Depression and Anxiety) that explained 84% of the total variance. Increasing PHQ-4 scores were strongly associated with functional impairment, disability days, and healthcare use. Anxiety had a substantial effect on functional status that was independent of depression. CONCLUSION The PHQ-4 is a valid ultra-brief tool for detecting both anxiety and depressive disorders.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

BACKGROUND The 4-item Patient Health Questionnaire-4 (PHQ-4) is an ultra-brief self-report questionnaire that consists of a 2-item depression scale (PHQ-2) and a 2-item anxiety scale (GAD-2). Given that PHQ-4, PHQ-2, and GAD-2 have not been validated in the general population, this study aimed to investigate their reliability and validity in a large general population sample and to generate normative data. METHODS A nationally representative face-to-face household survey was conducted in Germany in 2006. The survey questionnaire consisted of the PHQ-4, other self-report instruments, and demographic characteristics. RESULTS Of the 5030 participants (response rate=72.9%), 53.6% were female and mean (SD) age was 48.4 (18.0) years. The sociodemographic characteristics of the study sample closely match those of the total populations in Germany as well as those in the United States. Confirmatory factor analyses showed very good fit indices for a two-factor solution (RMSEA .027; 90% CI .023-.032). All models tested were structurally invariant between different age and gender groups. Construct validity of the PHQ-4, PHQ-2, and GAD-2 was supported by intercorrelations with other self-report scales and with demographic risk factors for depression and anxiety. PHQ-2 and GAD-2 scores of 3 corresponded to percentile ranks of 93.4% and 95.2%, respectively, whereas PHQ-2 and GAD-2 scores of 5 corresponded to percentile ranks of 99.0% and 99.2%, respectively. LIMITATION A criterion standard diagnostic interview for depression and anxiety was not included. CONCLUSIONS Results from this study support the reliability and validity of the PHQ-4, PHQ-2, and GAD-2 as ultra-brief measures of depression and anxiety in the general population. The normative data provided in this study can be used to compare a subjects scale score with those determined from a general population reference group.

Long-term prognosis in anorexia nervosa: lessons from a 21-year follow-up study

OBJECTIVE To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. METHOD Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. RESULTS In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. CONCLUSIONS Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

Long-term outcome of anorexia nervosa in a prospective 21-year follow-up study

In a prospective long-term follow-up of 84 patients 21 years after first hospitalisation for anorexia nervosa, we found that 50.6% had achieved a full recovery, 10.4% still met full diagnostic criteria for anorexia nervosa, and 15.6% had died from causes related to anorexia nervosa. Predictors of outcome included physical, social, and psychological variables.

Screening psychischer Störungen mit dem “Gesundheitsfragebogen für Patienten (PHQ-D)“

BACKGROUND Given our poor understanding of the very long-term course of anorexia nervosa. many questions remain regarding the potential for recovery and relapse. The purpose of the present study was to investigate long-term outcome and prognosis in an anorexic sample 21 years after the initial treatment. METHOD A multidimensional and prospective design was used to assess outcome in 84 patients 9 years after a previous follow-up and 21 years after admission. Among the 70 living patients, the follow-up rate was 90%. Causes of death for the deceased patients were obtained through the attending physician. Predictors of a poor outcome at the 21-year follow-up were selected based on the results of a previous 12-year follow-up of these patients. RESULTS Fifty-one per cent of the patients were found to be fully recovered at follow-up, 21% were partially recovered and 10% still met full diagnostic criteria for anorexia nervosa. Sixteen per cent were deceased, due to causes related to anorexia nervosa. The standardized mortality rate was 9.8. The three groups also showed significant differences in psychosocial outcome. A low body mass index and a greater severity of social and psychological problems were identified as predictors of a poor outcome. CONCLUSIONS Recovery is still possible for anorexic patients after a period of 21 years. On the other hand, patients can relapse, becoming symptomatic again despite previously achieving recovery status. Only a few patients classified as having a poor outcome were found to seek any form of treatment, therefore, it is recommended that these patients should be monitored regularly and offered treatment whenever possible.