Anxiety Disorders: Wittchen HU

Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU, Anonymous00170. · Division of Clinical Neurosciences, University of Southampton, Southampton, UK. · J Psychopharmacol. · Pubmed #16272179 No free full text.

Abstract: These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Borkovec TD, Rickels K, Stein DJ, Wittchen HU. · Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, SC 29425-0742, USA. · J Clin Psychiatry. · Pubmed #11414552 No free full text.

Abstract: OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in generalized anxiety disorder (GAD) and guide clinical practice with recommendations on the appropriate treatment strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R.T. Davidson, Yves Lecrubier, and David J. Nutt. Four additional faculty members invited by the chair were Karl Rickels, Hans-Ulrich Wittchen, Dan J. Stein, and Thomas D. Borkovec. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSIONS: GAD is the most common anxiety disorder in primary care and is highly debilitating. Furthermore, it is frequently comorbid with depression and other anxiety disorders, which exacerbates functional impairment. Antidepressants (serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and nonsedating tricyclic antidepressants) are generally the most appropriate first-line pharmacotherapy for GAD, since they are also effective against comorbid psychiatric disorders and are suitable for long-term use. Cognitive-behavioral therapy is the preferred form of psychotherapy for GAD, although when GAD is comorbid with depression, pharmacotherapy is increasingly indicated.

Wittchen HU, Gloster A, Beesdo K, Schönfeld S, Perkonigg A. · Institute of Clinical Psychology and Psychotherapy, Technische Universitaet Dresden, Dresden, Germany. · CNS Spectr. · Pubmed #19169189 links to  free full text

Abstract: We reviewed epidemiological findings for the diagnosis of posttraumatic stress disorder (PTSD) and its core diagnostic features, focusing on whether epidemiology has been helpful in clarifying some of the critical diagnostic issues relevant to the revision of the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases. Though epidemiology has provided increasingly rich data and knowledge regarding prevalence and incidence, patterns of onset and course, comorbidity, and risk factors for traumatic experiences and posttraumatic stress, little systematic research has been performed specifically addressing such critical diagnostic issues. Particularly, unresolved concerns remain regarding the definition of trauma, duration and impairment/distress criteria, the distinctiveness of the PTSD-syndrome, and even the position of PTSD in the classification system of mental disorders. A further exploitation of the existing data, and an improvement of existing epidemiological methods, strategies, and assessments are likely to substantially contribute to the clarification of unresolved diagnostic issues.

Goodwin GM, Anderson I, Arango C, Bowden CL, Henry C, Mitchell PB, Nolen WA, Vieta E, Wittchen HU. · University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK. · Eur Neuropsychopharmacol. · Pubmed #18501566 No free full text.

Abstract: DIAGNOSIS AND EPIDEMIOLOGY: DSM-IV, specifically its text revision DSM-IV-TR, remains the preferred diagnostic system. When employed in general population samples, prevalence estimates of bipolar disorder are relatively consistent across studies in Europe and USA. In community studies, first onset of bipolar mood disorder is usually in the mid-teenage years and twenties, and the occurrence of a major depressive episode or hypomania is usually its first manifestation. Since reliable criteria for delineating unipolar (UP) and bipolar (BI) depression cross-sectionally are currently lacking, there is a longitudinal risk - probably over 10% - that initial UP patients ultimately turn out as BP in the longer run. Its early onset implies a severe potential burden of disease in terms of impaired social and neuropsychological development, most of which is attributable to depression. BIPOLAR DEPRESSION IN CHILDREN: Bipolar I disorder is rare in prepubertal children, when defined according to unmodified DSM-IV-TR criteria. A broad diagnosis of bipolar disorder risks confounding with other childhood psychopathology and has less predictive value for bipolar disorder in adulthood than the conservative definition. Nevertheless, empirical studies of drug and other treatments and longitudinal studies to assess validity of the broadly defined phenotype in children and adolescents are desirable, rather than extrapolation from adult bipolar practice. The need for an increased capacity to conduct reliable trials in children and adolescents is a challenge to Europe, whose healthcare system should allow greater participation and collaboration than other regions, via clinical networks. ECNP will aspire to facilitate such developments. BIPOLAR DEPRESSION IN ADULTS - UNIPOLAR/BIPOLAR CONTRAST: Despite some differences in symptom profiles and severity measures, a cross-sectional categorical distinction between bipolar (BP) and unipolar (UP) depression is currently impossible. For regulatory purposes, a major depressive episode, meeting DSM-IV-TR criteria, remains the same diagnosis, irrespective of the overall course of the disorder. However, in refining diagnosis in future studies and DSM-V, a probabilistical approach to the UP/BP distinction is more likely to be informative as recommended by the International Society for Bipolar Disorders (ISBD). Anxiety is a commonly present, often at syndromal levels, in bipolar populations. Thus, RCT inclusion criteria for trials not targeting anxiety, should accept co-morbid anxiety disorders as part of the history and even current anxiety symptoms, where these are not dominating the mental state at recruitment to a study. Rapid cycling patients defined as those suffering from 4 or more episodes per year, may also be recruited into trials of bipolar depression without impairing assay sensitivity. Illness severity critically affects assay sensitivity. The minimum scores for entry into a bipolar depression trials should be >20 on HAM-D (17 item scale). However, efficacy is best detected in patients with HAM-D >24 at baseline. THE USE OF RATING SCALES IN BIPOLAR DEPRESSION: There is some dissatisfaction with the HAM-D or MADRS as the preferred primary outcome for trials, although they probably capture global severity adequately. Secondary measures to capture so-called atypical symptoms (such as hypersomnia or hyperphagia), or specific psychopathology more common in bipolar participants (such as lability of mood), could be informative as secondary measures. TREATMENT STUDIES IN BIPOLAR DEPRESSION: Monotherapy trials against placebo remain the gold-standard design for determining efficacy in bipolar depression. The confounding effects of co-medication are emerging from the literature on antidepressant studies in bipolar depression, often conducted in combination with antimanic agents to avoid possible switch to mood elevation. Three arm trials, including the compound to be tested, placebo, and a standard comparator, are generally preferred in order to ensure assay sensitivity and a better picture of benefit-risk ratio. However, in the absence of any gold-standard, two-arm trials may be enough. If efficacy happens to be proven as monotherapy, new compounds may be tested in adjunctive-medication placebo-controlled designs. Younger adults, without an established need for long-term medication, may be particularly suitable for clinical trials requiring placebo controls. The conversion rate of initial UP depression, converting to become BP in the long run is estimated to be 10%. Switch to mania or hypomania may be the consequence of active treatment for bipolar depression. Some medicines such as the tricyclic antidepressants and venlafaxine may be more likely to provoke switch than others, but this increased rate of switch may not be seen until about 10 weeks of treatment. Twelve week trials against placebo are necessary to determine the risk of switch and to establish continuing effects. Careful assessment at 6-8 weeks is required to ensure that patients who are failing to respond do not continue in a study for unacceptable periods of time. To capture a switch event, studies should include scales to define the phenomenology of the event (e.g. hypomania or mania) and its severity. These may be best applied shortly after the clinical decision that switch is occurring. Long-term treatment is commonly required in bipolar disorder. Trials to detect maintenance of effect or continued response in bipolar depression should follow a 'relapse prevention' design: i.e. patients are treated in an index episode with the medicine of interest and then randomized to either continue the active treatment or placebo. However, acute withdrawal of active medication after treatment response might artificially enhance effect size due to active drug withdrawal effects. A short taper is usually desirable. Longer periods of stabilisation are also desirable for up to 3 months: protocol compliance may then be difficult to achieve in practice and so will certainly make studies more difficult and expensive to conduct. The addition of a medicine to other agents during or after the resolution of a depressive or manic episode, and its subsequent investigation as monotherapy against placebo to prevent further relapse (as in the lamotrigine maintenance trials) is clinically informative. Assay sensitivity and patient acceptability are enhanced if the outcome in long-term studies is 'time to intervention for a new episode' for discontinuation designs.

Shear MK, Bjelland I, Beesdo K, Gloster AT, Wittchen HU. · School of Social Work, Columbia University, New York, USA. · Int J Methods Psychiatr Res. · Pubmed #17623395 No free full text.

Abstract: Anxiety disorders, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), comprise a relatively heterogeneous group of clinical conditions that range from specific phobias to obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). The grouping under one heading refers to the fact that these seemingly heterogeneous disorders share a number of common psychopathological features and also share at least some common principles in treatment. Among the shared elements are broadly defined prototypical anxiety reactions, panic attacks, anticipatory anxiety, avoidance behaviour, a predominantly early onset, and relatively high persistence rates over time. Many of the shared diagnostic features of anxiety disorders are by their nature dimensional, and hundreds of psychometric scales have been developed to measure these diagnostic constructs across anxiety disorder and for specific diagnostic classes. This paper explores different types of dimensional approaches used in the literature and discusses how an integrated categorical/dimensional strategy might enhance the usefulness of the DSM-V. We suggest the use of cross-cutting dimensional ratings that might ultimately lead to an improved classification model. We also suggest that a staging approach to illness, based upon supplementary dimensional rating could provide useful information for clinical and research purposes.

Hoffman DL, Dukes EM, Wittchen HU. · Independent Outcomes Research Consultant, New Haven, CT, USA. · Depress Anxiety. · Pubmed #17146763 No free full text.

Abstract: The goal of the current work is to provide a comprehensive review and interpretation of the literature on the human and economic burden of generalized anxiety disorder (GAD) and how it compares with that of other mental disorders. The term "human burden" is used to describe quantified impairments in role functioning and quality of life (QOL). "Economic burden" describes costs related to health care resource utilization and lost work. A review of 34 studies reporting original quantitative data on associations between GAD and role functioning, QOL, and/or economic costs was undertaken. GAD was defined by DMS-III-R, DSM-IV, or ICD-10 DCR. Persons with GAD (both with and without a comorbid mental disorder) described significant impairments due to both physical and emotional problems. Studies typically showed that role and QOL impairments of GAD were at least comparable in magnitude to those of other anxiety disorders, somatoform disorders, and physical conditions, and greater than those of substance use disorders. Large representative studies showed that role impairments of pure GAD were similar in magnitude to those of pure MDD. Studies of DSM-IV disorders showed that QOL impairments of GAD were at least comparable in magnitude to those of MDD; studies of DSM-III-R disorders showed the opposite pattern. GAD was associated with considerable economic costs owing to lost work productivity and high medical resource use. Quality of care initiatives that have been implemented to increase recognition and improve treatment outcomes for persons with MDD should be extended to the effective management of GAD.

Fröhlich C, Jacobi F, Wittchen HU. · Technische Universität Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #16328107 No free full text.

Abstract: BACKGROUND: Despite an abundance of questionnaire data, the prevalence of clinically significant and medically unexplained pain syndromes in the general population has rarely been examined with a rigid personal-interview methodology. OBJECTIVE: To examine the prevalence of pain syndromes and DSM-IV pain disorder in the general population and the association with other mental disorders, as well as effects on disability and health-care utilization. METHODS: Analyses were based on a community sample of 4.181 participants 18-65 years old; diagnostic variables were assessed with a standardized diagnostic interview (M-CIDI). RESULTS: The 12-month prevalence for DSM-IV pain disorder in the general population was 8.1%; more than 53% showed concurrent anxiety and mood disorders. Subjects with pain disorder revealed significantly poorer quality of life, greater disability, and higher health-care utilization rates compared to cases with pain below the diagnostic threshold. The majority had more than one type of pain, with excessive headache being the most frequent type. CONCLUSIONS: Even when stringent diagnostic criteria are used, pain disorder ranks among the most prevalent conditions in the community. The joint effects of high prevalence in all age groups, substantial disability, and increased health services utilization result in a substantial total burden, exceeding that of depression and anxiety.

Wittchen HU, Jacobi F. · Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany. · Eur Neuropsychopharmacol. · Pubmed #15961293 No free full text.

Abstract: Epidemiological data on a wide range of mental disorders from community studies conducted in European countries are presented to determine the availability and consistency of prevalence, disability and treatment findings for the EU. Using a stepwise multimethod approach, 27 eligible studies with quite variable designs and methods including over 150,000 subjects from 16 European countries were identified. Prevalence: On the basis of meta-analytic techniques as well as on reanalyses of selected data sets, it is estimated that about 27% (equals 82.7 million; 95% CI: 78.5-87.1) of the adult EU population, 18-65 of age, is or has been affected by at least one mental disorder in the past 12 months. Taking into account the considerable degree of comorbidity (about one third had more than one disorder), the most frequent disorders are anxiety disorders, depressive, somatoform and substance dependence disorders. When taking into account design, sampling and other methodological differences between studies, little evidence seems to exist for considerable cultural or country variation. Disability and treatment: despite very divergent and fairly crude assessment strategies, the available data consistently demonstrate (a) an association of all mental disorders with a considerable disability burden in terms of number of work days lost (WLD) and (b) generally low utilization and treatment rates. Only 26% of all cases had any consultation with professional health care services, a finding suggesting a considerable degree of unmet need. The paper highlights considerable future research needs for coordinated EU studies across all disorders and age groups. As prevalence estimates could not simply be equated with defined treatment needs, such studies should determine the degree of met and unmet needs for services by taking into account severity, disability and comorbidity. These needs are most pronounced for the new EU member states as well as more generally for adolescent and older populations.

Fehm L, Pelissolo A, Furmark T, Wittchen HU. · Department of Psychology, Humboldt-University Berlin, Rudower Chaussee 18, D-12489 Berlin, Germany. · Eur Neuropsychopharmacol. · Pubmed #15921898 No free full text.

Abstract: This paper provides a critical review of the prevalence of social phobia in European countries, a description of associated disability and burden and of clinical correlates and risk factors associated with social phobia. On the basis of a comprehensive literature search we identified 21 community studies and two primary care studies. The median lifetime and 12-month prevalence rates of social phobia in community samples referring to DSM-III-R and DSM-IV criteria were 6.65% and 2.0%, respectively. Younger individuals showed the highest rates, and women were more frequently affected than men. Social phobia was shown to be a persistent condition with a remarkably high degree of comorbid conditions, associated impairment and disability. Research deficits lie in a lack of data for most EU countries and in a lack of studies in children and the elderly. No data are available addressing met and unmet needs for intervention and costs, and data for vulnerability and risk factors of malignant course are scarce.

Wittchen HU, Beesdo K, Bittner A, Goodwin RD. · Institute of Clinical Psychology and Psychotherapy, Dresden University of Technology, Chemnitzerstrasse 46, 01187 Dresden, Germany. · Eur Psychiatry. · Pubmed #14680714 No free full text.

Abstract: Anxiety and depressive disorders are common mental disorders in general population, imposing tremendous burden on both affected persons and society. Moreover, comorbidity between anxiety and depressive conditions is high, leading to substantial disability and functional impairment. Findings consistently suggest that anxiety disorders are primary to depression in the majority of comorbid cases. Yet, the question of whether anxiety disorders are risk factors for depression, and potentially even causal risk factors for the first onset of depression, remains unresolved. Recent results have shown that anxiety disorders increase the risk for subsequent depression, and also affect the course of depression, resulting in a poorer prognosis. Further, some results suggest a dose-response-relationship in revealing that a higher number of anxiety disorders and more severe impairment associated with anxiety disorders additionally increase the risk for subsequent depression. The goal of this paper is to review recent literature, summarize implications of previous findings, and suggest directions for future research regarding preventive and intervention strategies.

Merikangas KR, Lieb R, Wittchen HU, Avenevoli S. · Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-2670, USA. · Acta Psychiatr Scand Suppl. · Pubmed #12950434 No free full text.

Abstract: OBJECTIVE: To present data on the role of familial factors in the etiology of social anxiety disorder. METHOD: Findings presented from a family/high-risk study (the Yale Family Study) and a prospective community study of youth (the Munich Early Developmental Stages of Psychopathology (EDSP) Study). RESULTS: The Yale Family Study demonstrated a substantial degree of familial aggregation of social anxiety disorder and specificity with respect to other anxiety subtypes among adult relatives. The Yale high-risk component and the EDSP Study confirm the association between parental and offspring social anxiety, but did not yield consistent evidence for an association between familial environmental factors and social anxiety. CONCLUSION: Future studies are needed to examine mechanisms for the specificity of social anxiety disorder aggregation, to identify vulnerability factors for its development and to pinpoint environmental conditions that may enhance or suppress expression of underlying vulnerability.

Wittchen HU, Fehm L. · Department of Clinical Psychology and Psychotherapy, Dresden University of Technology, Chemnitzer Str. 46, Dresden, Germany. · Acta Psychiatr Scand Suppl. · Pubmed #12950432 No free full text.

Abstract: OBJECTIVE: To summarize epidemiological studies providing data on prevalence, incidence, comorbidity, natural course, risk factors and consequences of social phobia (SP). METHOD: Data from cross-sectional studies and prospective longitudinal studies in particular are considered. RESULTS: These studies portray SP as a frequent mental disorder, which begins typically in early adolescence, and is highly comorbid with other anxiety disorders, as well as secondary depression and substance abuse disorders. Several possible risk factors have already been identified for the onset and unfavorable course of SP; some of them have been tested in prospective longitudinal studies. SP is a chronic disorder when compared with other mental disorders and when subclinical symptomatic levels are considered. Impairment caused by SP is considerable and increases over a patient's life span. The negative impact of SP is not only reflected in subjective well-being and reduced quality of life but also in social role functioning, and it impacts negatively on career progression. CONCLUSION: Prospective longitudinal studies in representative samples drawn from the general population provide information that allows the overall direct and indirect costs of the disorder (treatment costs, disability, social welfare) to be determined, and enables an improvement in long-term care strategies as well as preventive efforts to be established.

Nutt DJ, Ballenger JC, Sheehan D, Wittchen HU. · School of Medical Sciences, University of Bristol, UK. · Int J Neuropsychopharmacol. · Pubmed #12466031 No free full text.

Abstract: Generalized anxiety disorder (GAD) is a severe and chronic anxiety disorder characterized by uncontrollable worrying and somatic anxiety (tension, insomnia and hypervigilance). It is a common condition, with lifetime prevalence rates for DSM-IV GAD in the general population of approx. 5-6% being reported. In addition, like other anxiety disorders, GAD also shows comorbidity with depression and most of the other anxiety disorders. This article reviews data on the prevalence of GAD, its comorbidity with depression, and its social and economic impact. Proposed neurobiological mechanisms for GAD are discussed, since an understanding of these may help in the development of future therapies. Finally, current pharmacological and non-pharmacological treatment options for GAD are reviewed, with particular attention being paid to published clinical-trial data.

Barkow K, Heun R, Ustün TB, Gänsicke M, Wittchen HU, Maier W. · Department of Psychiatry, University of Bonn, Germany. · Acta Psychiatr Scand. · Pubmed #12121209 No free full text.

Abstract: OBJECTIVE: To investigate reliability of self-reported age at onset of frequent mental disorders and its association with patient and disorder characteristics. METHOD: A total of 1031 primary care patients with at least one lifetime psychiatric diagnosis were asked to report age at onset of their disorders at baseline and after 1 year. Intraclass correlation coefficients (ICC) for age at onset information were calculated for individual disorders. RESULTS: ICC were high and lay between 0.6790 (generalized anxiety disorder) and 0.7977 (dysthymia). Factors associated with reliability are different for different disorders: gender for depressive episodes, gross national product per year per inhabitant for dysthymia, age for pain disorder, years of formal education for dysthymia, generalized anxiety disorder, and agoraphobia, and number of lifetime diagnoses for depression and agoraphobia. CONCLUSION: Self-reported age at onset is reliable. Further research on factors associated with reliability should focus on interview conditions and subject parameters during interview.

Kessler RC, Wittchen HU. · Department of Health Care Policy, Harvard Medical School, Boston, Mass. 02115, USA. · J Clin Psychiatry. · Pubmed #12044107 No free full text.

Abstract: BACKGROUND: Although generalized anxiety disorder (GAD) is at least twice as prevalent as panic disorder and is among the commonly occurring mental disorders, changing diagnostic criteria have hampered the cumulation of data on patterns and correlates. METHOD: A computer literature search was carried out for the terms generalized anxiety disorder and GAD in the MEDLINE and PsycLIT databases. Reports published in English since 1995 were reviewed to determine patterns and correlates of GAD in the general population. RESULTS: The literature shows clearly that GAD is a commonly occurring disorder associated with serious impairment. Although the high comorbidities of GAD with other disorders in clinical samples led to speculation that the impairments associated with GAD were due to comorbid conditions, several recent studies show that pure GAD is associated with serious impairments. Considerable uncertainty remains regarding appropriate diagnostic criteria. The requirements that the anxiety be excessive and persist for 6 months are the subject of the most controversy. Recently reported community epidemiologic data show that generalized anxiety syndromes that persist for shorter time periods and that are not excessive in relation to objective stressors are as seriously impairing as syndromes that meet full criteria for GAD. It is less clear whether currently available treatments are as useful in resolving episodes of generalized anxiety that lie outside the boundaries of current ICD and DSM criteria. CONCLUSION: GAD is a commonly occurring mental disorder that can seriously impair functioning. Coordinated community epidemiologic studies and treatment effectiveness studies are needed to resolve remaining uncertainties regarding the diagnostic boundaries of GAD.

Wittchen HU, Holsboer F, Jacobi F. · Institute of Clinical Psychology and Psychotherapy, Technical University of Dresden, Germany. · J Clin Psychiatry. · Pubmed #11775090 No free full text.

Abstract: Numerous epidemiologic studies have revealed the high prevalence of depressive disorders despite the availability of several treatment options that have been proved to be efficacious and safe. The persistence of depression, at a time when treatment options have increased, suggests that there are unmet needs in the clinical management of depression. Aside from improving treatment guidelines, the role of primary care physicians should be redefined to ensure that lifetime depressive disorders are more frequently recognized, diagnosed, and appropriately treated and managed, either by these clinical "gatekeepers" or through referrals to mental health specialists. With this management strategy, access to care can be broadened to include not only the severely ill, but also patients in earlier stages of their depressive illness process who might profit most from modern treatment methods.

Wittchen HU, Fehm L. · Department of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany. · Psychiatr Clin North Am. · Pubmed #11723624 No free full text.

Abstract: Social phobia is a common condition, with current prevalence estimates in the range of 4% to 6% and a lifetime risk of 7% to 13%. It has an early onset and, without appropriate intervention, it has a disproportionately higher risk for persistence compared with other anxiety disorders. Presentation differs between age groups; the disorder in teenagers and in those in their early 20s tends to look different in terms of types of problems and the associated distress to that expected in the 30s and 40s age groups, when these individuals have already endured 20 years of suffering and disability. There is an increased risk for depression and substance abuse disorders even in adolescence, in addition to an increased risk for psychosocial impairment and disability resembling that experienced by depressed outpatients. This finding is particularly true in cases affected by generalized SP, which might have slightly different etiologic pathways than the nongeneralized type. Social phobia is in itself a disabling disorder, and individuals who develop comorbid conditions have a more severe level of disability. Early recognition, diagnosis, and treatment of SP could minimize sufferers' problems throughout their subsequent lives, preventing the development of comorbidity and a worsened prognosis. Developing models for early recognition and treatment should improve the outcome for the patient, as well as reduce future demand on health care resources. Epidemiologic studies, with their methodologic strengths and unique methods, can be instrumental in this respect. They may, for example, provide time-efficient, simple screening tools for use by physicians or even patients, based on the existing diagnostic instruments used in epidemiologic surveys. They may provide further guidance in making treatment decisions and developing treatment algorithms by offering criteria, which with additional vulnerability and risk factors, will lead to more severe, chronic, and comorbid course in a given case.

Wittchen HU, Hoyer J. · Institute of Clinical Psychology and Psychotherapy, Technical University of Dresden, Germany. · J Clin Psychiatry. · Pubmed #11414546 No free full text.

Abstract: Generalized anxiety disorder (GAD) is a chronic and highly prevalent disorder in the adult population, 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 disorder. Despite changes in diagnostic criteria, estimates of prevalence for GAD are remarkably consistent 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 depression and other anxiety and somatoform disorders. Significant GAD-specific disability occurs even when comorbidity is not present.

Kessler RC, Keller MB, Wittchen HU. · Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts, USA. · Psychiatr Clin North Am. · Pubmed #11225507 No free full text.

Abstract: The literature reviewed here is consistent in showing that GAD is a common mental disorder that typically has an early age of onset, a chronic course, and a high degree of comorbidity with other anxiety and mood disorders. Comorbid GAD is often temporally primary, especially in relation to mood disorders, and is associated with an increased risk for the subsequent onset and severity of secondary disorders. The weight of evidence reviewed here argues against the view expressed by early commentators that GAD is better conceptualized as a prodrome, residual, or severity marker of other disorders than as an independent disorder. Focused studies of comorbidity between GAD and major depression, in which comorbidity is high, lead to the same conclusion. The crucial evidence for this conclusion includes the following: 1. Contrary to the findings of clinical studies, GAD in the community does not have a higher comorbidity than do most other anxiety or mood disorders. 2. The symptoms of GAD form an empiric cluster distinct from the symptoms of major depression in studies of symptom profiles. 3. Family studies show distinct aggregation of GAD and major depression. 4. Twin studies show that the environmental determinants of GAD are different from the environmental determinants of major depression. 5. The sociodemographic predictors of GAD in epidemiologic studies are different from the predictors of major depression. 6. The clinical course of GAD is less consistently related to comorbidity than is the course of other anxiety and mood disorders. 7. The impairments associated with GAD are equivalent to, or greater than, those associated with other severely impairing chronic physical and mental disorders. These findings show that the status of GAD as an independent disorder is at least as strongly supported by available evidence as is that of other anxiety or mood disorders. This article also shows that uncertainty remains regarding even the basic epidemiologic characteristics of the GAD syndrome. Lingering concerns about the independence of GAD have conspired to exacerbate this problem by promoting repeated changes in the diagnostic criteria for GAD from the DSM-III to DSM-III-R and to DSM-IV. These successive changes have made it difficult to amass consistent long-term data on the natural history of GAD. Available evidence on the empiric validity of current diagnostic thresholds for GAD raises questions about the requirements, such as whether a 6-month minimum duration and four or more additional psychophysiologic symptoms are optimal for identifying all of the people in the general population who suffer from a clinically significant GAD syndrome. An additional source of potential bias in this regard is that the DSM system requires that anxiety be excessive or unrealistic for a diagnosis of GAD. Interestingly, there is no comparable DSM requirement that dysphoria must be excessive or unrealistic to qualify as major depression. These diagnostic uncertainties make it difficult to gain a clear understanding of the true breadth and depth of the GAD syndrome in the general population. Additional research is needed, ideally from unbiased epidemiologic samples, to resolve these basic uncertainties. The strong comorbidity between GAD and major depression, the fact that most people with this type of comorbidity report that the onset of GAD occurred before the onset of depression, and the fact that temporally primary GAD significantly predicts the subsequent onset of depression and other secondary disorders raise the question of whether early intervention and treatment of primary GAD would effectively prevent the subsequent first onset of secondary anxiety and depression. Unfortunately, little is known about this possibility because, as mentioned earlier, few people with pure GAD seek treatment. Why this is true is unknown. Given the early onset of GAD and its strong effects in predicting the subsequent onset, severity, and persistence of other disorders, efforts are needed to collect epidemiologic data on the reasons for the low rate of help seeking among people with pure GAD and to develop outreach strategies that may correct this situation.

Wittchen HU. · Institute of Clinical Psychology and Psychotherapy, Technical University of Dresden, Munich, Germany. · Int Clin Psychopharmacol. · Pubmed #10994677 No free full text.

Abstract: Social anxiety disorder, also known as social phobia, is one of the most prevalent anxiety disorders, affecting 7-13% of subjects in the community at some time in their lives. Despite being eminently treatable, it remains largely under-recognised and, therefore, undertreated. The disorder is characterized by a fear of scrutiny by others, with sufferers experiencing excessive anxiety in social and performance situations. This excessive anxiety usually leads to avoidance behaviour that can severely affect normal daily living. With onset commonly occurring during childhood or adolescence, social anxiety disorder may disrupt normal patterns of development of social and personal relationships, often having a long-term impact on emotional stability in social or working life. If left untreated, the course of social anxiety disorder is frequently complicated with comorbid conditions, particularly major depression or substance abuse. This review assesses the size of the clinical problem by evaluating current and lifetime prevalence estimates, age of onset, risk factors and evolution of the clinical course; thereby providing the rationale for early recognition and prompt treatment.

Brunello N, den Boer JA, Judd LL, Kasper S, Kelsey JE, Lader M, Lecrubier Y, Lepine JP, Lydiard RB, Mendlewicz J, Montgomery SA, Racagni G, Stein MB, Wittchen HU. · Centre of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. · J Affect Disord. · Pubmed #10940449 No free full text.

Abstract: Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure.The most recent drug class to be investigated for the psychopharmacological treatment of social phobia is the SSRI group for which there is growing support. The other drug classes that have been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and beta-blockers. The SSRIs represent a new and attractive therapeutic choice for patients with generalized social phobia. Recently the first, large scale, placebo-controlled study to assess the efficacy of drug treatment in generalized social phobia has been completed with paroxetine. Paroxetine was more effective in reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs as the drugs of choice in social phobia because of their effectiveness and because they avoid the problems of treatment with benzodiazepines or classical MAOIs.

Lecrubier Y, Wittchen HU, Faravelli C, Bobes J, Patel A, Knapp M. · Inserm, Hôpital de la Salpêtrière, Paris, France. · Eur Psychiatry. · Pubmed #10713797 No free full text.

Abstract: Epidemiologic surveys conducted across Europe indicate that the lifetime prevalence of social anxiety disorder in the general population is close to 7%. The disorder in adulthood rarely presents in its 'pure' form and 70-80% of patients have at least one other psychiatric disorder, most commonly depression. Social anxiety disorder is a risk factor for the development of depression and alcohol/substance use or dependence, especially in cases with an early onset (< 15 years). Individuals with social anxiety disorder have significant functional impairment, notably in the areas of initiation and maintenance of social/romantic relationships and educational and work achievement. The economic consequences of social anxiety disorder are considerable, with a high level of diminished work productivity, unemployment and an increased utilisation of medical services amongst sufferers. Effective treatment of social anxiety disorder would improve its course and its health and economic consequences.

Davidson JR, Wittchen HU, Llorca PM, Erickson J, Detke M, Ball SG, Russell JM. · Department of Psychiatry, Duke University Medical School, Durham, NC 27710, USA. · Eur Neuropsychopharmacol. · Pubmed #18559291 No free full text.

Abstract: The objective was to examine duloxetine 60-120 mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (>or=50% reduction in Hamilton Anxiety Rating Scale total score to <or=11 and "much"/"very much improved" ratings for the last 2 visits of open-label phase) were randomly assigned to receive duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as >or=2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P<or=0.001) and worsened on each outcome measure (P<or=0.001, all comparisons). Duloxetine 60-120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.

Zimmermann U, Spring K, Wittchen HU, Holsboer F. · Max-Planck-Institute of Psychiatry, Munich, Germany. · Alcohol Clin Exp Res. · Pubmed #15084900 No free full text.

Abstract: BACKGROUND: The high rate of comorbidity between alcoholism and anxiety disorders suggests some causal link. This study used the startle reflex to investigate whether increased reactivity to stimuli inducing fear or related affective states might be one mechanism by which a family genetic risk promotes the development of alcohol use disorders. METHODS: Thirty-one sons of alcoholics (PH+) were recruited from the participants of a longitudinal epidemiologic survey representative of the Munich area population between 18 and 25 years. Thirty male low-risk participants without parental alcoholism (PH-) were matched for age and history of psychiatric disorders. The baseline acoustic startle reflex was elicited before and after subjects drank 0.6 g/kg ethanol or placebo in a randomized, double-blind, placebo-controlled crossover design. Thereafter, the startle response was investigated while the subjects' affective state was manipulated by announcement of aversive electric finger stimuli to induce fear potentiation and by presentation of photographic slides previously rated to be pleasant, unpleasant, or neutral in their emotional valence. RESULTS: Plain startle response was lower in PH+ than PH- participants and was equally dampened by alcohol in PH+ and PH- subjects. Threat of finger shocks increased the startle response to the same extent in both groups. This fear potentiation effect was significantly attenuated by alcohol given on the second experimental day but not if alcohol was administered first and placebo on the second day. Pleasant and unpleasant slides decreased and increased startle response, respectively, and this effect was influenced by neither risk group nor alcohol. CONCLUSIONS: The acoustic startle reflex seems to be reduced in sons of alcoholics. The nonsignificant results during startle modification do not support the concept of increased reactivity to anxiety-related environmental stimuli as a mechanism promoting alcohol use disorders in subjects at increased family genetic risk for alcoholism.

Rabung S, Harfst T, Kawski S, Koch U, Wittchen HU, Schulz H. · Institut und Poliklinik für MedizinischePsychologie, Universitätsklinikum Hamburg Eppendorf, Martinistr., D-20246 Hamburg, Germany. · Z Psychosom Med Psychother. · Pubmed #19402020 No free full text.

Abstract: OBJECTIVES: The HEALTH questionnaire, which originally consisted of 79 items, aims to assess generic aspects of psychosocial health. METHODS: Based on large clinical and healthy samples (n = 1548 psychotherapy inpatients, n = 5630 primary-care patients), the questionnaire was shortened and psychometrically analyzed. RESULTS: The resulting 49-item questionnaire ("HEALTH-49") comprises six discrete modules with nine scales (somatoform complaints, depressiveness, phobic anxiety, psychological wellbeing, interactional problems, self-efficacy, activity and participation, social support, and social stress). It proves to be well accepted and feasible under routine conditions. Factor analyses confirm the intended dimensional configuration and the relative independence of modules. The scales reveal high reliability. Evidence of their validity and sensitivity to change are demonstrated. CONCLUSIONS: The HEALTH-49 is a self-rating instrument that allows for the comprehensive and economic assessment of generic aspects of psychosocial health. It is highly suitable for use in clinical practice. The questionnaire is available as a free download from http://www.hamburger-module.de/