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Objective: The aim of the bereavement exclusion criterion for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) major depressive episode (MDE) is to identify subjects with a modest, self-limited, "normal" depressive syndrome. One would therefore expect less severe depressive symptoms and a different and better outcome for bereaved subjects who were excluded from the diagnosis of MDE as compared to MDE controls. In a previous cross-sectional study, we have shown such expectations were not met. Herein, we further challenge the accuracy of the bereavement exclusion criterion regarding response to treatment., Method: In a database of 12,615 subjects seeking treatment for depression, 1,138 (9.0%) individuals met DSM-IV MDE criteria except the bereavement exclusion criterion. This sample was matched for age, gender, educational level, and number of previous depressive episodes with 1,138 MDE patients. The bereavement exclusion and MDE groups were prospectively assessed for outcome after 6 weeks of treatment. Primary outcome measures included the number of DSM-IV MDE symptoms and the presence/absence of DSM-IV MDE Criterion A symptoms at follow-up., Results: The bereavement exclusion individuals had higher levels of DSM-IV MDE symptoms (P = .005) and self-rated depression (P < .0001) than MDE controls. Both groups had a similar 6-week outcome: 37.7% versus 39.9%, respectively, were responders to treatment, and 80.1% versus 82.2% no longer had the MDE DSM-IV symptom criteria at follow-up (P = .33)., Conclusions: The DSM-IV bereavement exclusion for MDE is inadequate according to response to treatment, at least in this sample of individuals seeking treatment for depressive symptoms. It is proposed that bereavement, just as any stressful event, could be noted but without its affecting the treatment decision., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

This article compares the preliminary, descriptive European Study of The Epidemiology of Mental Disorders (ESEMeD) findings reported in this supplement with 8 broad patterns of results found in previous psychiatric epidemiologic surveys. It is a systematic review of the literature on community epidemiologic surveys of anxiety and mood disorders. It concludes that the ESEMeD findings are broadly consistent with the patterns found in previous surveys but faults the preliminary ESEMeD analyses for failing to distinguish cases by severity and to consider the effects of severity on need for treatment. The fact that the ESEMeD surveys collected much richer data than previous psychiatric epidemiologic surveys on role impairment, symptom severity, and episode duration makes it possible to develop more useful classifications of clinical severity in future analyses. Elaborations that feature such distinctions have the potential to substantially increase the relevance of the ESEMeD findings for European health care policy.

Background: The placebo response rate has increased in several psychiatric disorders and is a major issue in the design and interpretation of clinical trials. The current investigation attempted to identify potential predictors of placebo response through examination of the placebo-controlled clinical trial database for escitalopram in 3 anxiety disorders and in major depressive disorder (MDD)., Method: Raw data from placebo-controlled studies (conducted from 2002 through the end of 2004) of escitalopram in patients meeting DSM-IV criteria for MDD and anxiety disorders (generalized anxiety disorder [GAD], social anxiety disorder [SAD], panic disorder) were used. Potential predictors examined were type of disorder, location of study, dosing regimen, number of treatment arms, gender of patients, and duration and severity of disorder., Results: Placebo response (defined as the percent decrease from baseline in the reference scale) was higher in GAD and MDD studies conducted in Europe (p < .0001 and p = .0006, respectively) and was not associated with gender or duration of episode. In GAD, the placebo response rate was higher in a European fixed-dose study, which also had more treatment arms. In SAD and in U.S. specialist-treated MDD, a higher placebo response rate was predicted by decreased baseline disorder severity., Conclusion: Additional work is needed before definitive recommendations can be made about whether standard exclusion criteria in clinical trials of antidepressants, such as mild severity of illness, maximize medication-to-placebo differences. This analysis in a range of anxiety disorders and MDD suggests that there may be instances in which the predictors of placebo response rate themselves vary across different conditions.

Background: Two recent reanalyses of epidemiologic studies found that adding a clinical significance criterion reduced disorder prevalence. Patients presenting for clinical care are usually distressed or impaired by their symptoms; thus, the DSM-IV clinical significance criterion might have little impact on diagnosis in clinical practice. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examine the impact of the DSM-IV clinical significance criterion on diagnostic frequencies of depressive and anxiety disorders in psychiatric outpatients., Method: 1500 psychiatric outpatients were evaluated with the Structured Clinical Interview for DSM-IV. We determined the percentage of patients who met symptom criteria but did not meet the DSM-IV clinical significance criterion for major depressive disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), social phobia, specific phobia, panic disorder, and obsessive-compulsive disorder., Results: No patient who met the symptom criteria for current major depressive disorder or PTSD failed to meet the clinical significance criterion. Less than 2% of patients meeting the symptom criteria for current GAD did not meet the clinical significance criterion. There was variability among the remaining anxiety disorders in the percentage of symptomatic patients who met the clinical significance criterion., Conclusion: In psychiatric patients, the clinical significance criterion had little impact on diagnosing major depressive disorder, GAD, and PTSD, disorders that are defined, in part, by disruptions of daily regulatory domains such as sleep, appetite, energy, and concentration. In contrast, the clinical significance criterion had a greater impact in determining whether phobic fears, obsessive thoughts, and panic attacks were sufficiently distressing or impairing to qualify for disorder status.

At the Sixth International Obsessive-Compulsive Disorder Conference (IOCDC), held November 13-15, 2003, in Lanzarote, Spain, 2 issues were discussed that are of great importance to future research on obsessive-compulsive disorder (OCD). The first of these is the possible inclusion of obsessive-compulsive spectrum disorders (OCSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. OCSD resemble OCD in their clinical symptoms, associated features, comorbidity, family/genetics, etiology, and neurocircuitry, as well as their selective response to treatment with serotonin reuptake inhibitors. The second issue is considering remission as the ultimate goal of treatment for OCD instead of just symptom reduction, as has been suggested in other disorders. These and other issues should be discussed at future meetings of the IOCDC and influence how we conceptualize the disorder and design future treatment trials.

Generalized, persistent, and free-floating anxiety was first described by Freud in 1894, although the diagnostic term generalized anxiety disorder (GAD) was not included in classification systems until 1980 (Diagnostic and Statistical Manual for Mental Disorders, Third Edition [DSM-III]). Initially considered a residual category to be used when no other diagnosis could be made, it is now widely accepted that GAD represents a distinct diagnostic category. Since 1980, revisions to the diagnostic criteria for GAD in the DSM-III-R and DSM-IV classifications have markedly redefined this disorder, increasing the duration criterion to 6 months and increasing the emphasis on worry and psychic symptoms. This article reviews the development of the diagnostic criteria for defining GAD from Freud to DSM-IV and compares the DSM-IV criteria with the criteria set forth in the tenth revision of the International Classification of Diseases. The impact of the changes in diagnostic criteria on research into GAD, and on diagnosis, differential diagnosis, and treatment of GAD, will be discussed.

The complexity of subtyping depression and the implications that such subtyping has on treatment choices are discussed in this article. The most recent edition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) directs clinicians to classify the mood disorders in depressed patients as unipolar, bipolar, due to a general medical condition, or due to substance abuse. The focus of this article is unipolar (major depression and dysthymia) and bipolar I and II disorders with and without feature specifiers for atypical depression, seasonal affective disorder, psychotic depression, and postpartum depression. Anxious depression, which is not a DSM-IV classification, is also reviewed.

Nearly 50% of individuals in the community meet threshold or subthreshold diagnostic criteria for depression or anxiety, with depression being far more common. Co-occurrence of anxiety and depression is common, as the majority of individuals who experience anxiety also manifest threshold- or subthreshold-level depression. In the current study, addition of subthreshold categories improved the coverage of treated cases in the community by nearly a third; 61% of subjects were diagnosed according to threshold criteria while 89% were diagnosed according to subthreshold categories. These results suggest that inclusion of subthreshold-level syndromes enhances the validity of diagnostic systems by increasing the proportion of treated cases that meet diagnostic criteria and by providing a more accurate representation of milder syndromes of depression and anxiety.

International epidemiologic and clinical studies have shown that comorbid depression and anxiety is of major importance, resulting in more severe symptoms, impairment, subjective distress, and longitudinal course than either anxiety or depression alone. Threshold and subthreshold levels of anxiety ("A," "a") and depression ("D," "d") can be defined on the basis of duration, frequency, impairment, and number of symptoms. These letters can then be used to designate the various combinations of depression and anxiety, e.g., AD, aD. Current evidence demonstrates the importance of evaluating both threshold and subthreshold levels of depression and anxiety.

On the basis of our long-term experience in treating family-practice patients and conducting clinical research with them, we propose a practical clinical nosology that takes into account the subsyndromal spectrum of generalized anxiety, as well as patterns of illness, particularly for the family-practice setting. We present an alternative proposal of how to conceptualize generalized anxiety disorders clinically into acute anxiety, subacute anxiety, chronic anxiety, and double anxiety. This is followed by a discussion of the implications for choosing from among the various anxiolytic treatment options available to the family physician and of the importance of the therapeutic context in which treatment is provided. Anxiolytics are not a panacea, but only tools to allow the patient to help himself or herself. Irrespective of which anxiolytic is chosen, and irrespective of the chronicity of the anxiety, short-term (2 to 6 weeks) anxiolytic therapy--if necessary provided more than once on an intermittent basis--should be the treatment approach of first choice. Data are presented to suggest that 50% of all chronically ill patients who have generalized anxiety disorder could benefit from such a treatment approach.

Background: Anxiety disorders are known to commonly coexist in individuals, both with other anxiety disorders and with mental disorders from other groupings, such as affective disorders. We questioned how frequently anxiety disorders actually occur in isolation, as "pure cultures.", Method: We examined diagnostic patterns among the 711 subjects entered into a large, multicenter study of anxiety disorders, the Harvard/ Brown Anxiety Disorders Research Program (HARP), which focused on panic, agoraphobia, generalized anxiety disorder, and social phobias as "index disorders" required for intake., Results: We used various definitions for "pure culture." By all definitions, subjects with "pure culture" represented a minority, especially in cases of generalized anxiety disorder and social phobia, where comorbidity was virtually ubiquitous. "Pure culture" status was associated with later onset of illness and less chronicity., Conclusion: Future studies of anxiety disorder should aim to document the extensive comorbidity, rather than eliminate it by restrictive diagnostic exclusion criteria, lest they yield atypical or even misrepresented groups of patients. Clinicians should not stop at identifying only the "main" diagnosis but look for other, comorbid diagnoses that are often present.

Background: The comorbidity of substance abuse or dependence and psychiatric illness can complicate the diagnosis, clinical course, and treatment of dually diagnosed patients. In this study, we examined the relationship between substance use disorder (SUD) and psychopathology in an outpatient psychiatric setting., Method: Among 391 patients evaluated at an anxiety and effective disorders clinic, 54 patients met DSM-III-R criteria for lifetime substance use disorder and current unipolar depression or anxiety disorder. We selected 54 sex- and age-matched controls with psychiatric illness without SUD as a comparison group. All patients were given a structured diagnostic interview and symptom rating scales. In addition to comparing dual and single diagnosis groups, we compared those within the dual diagnosis group and those with primary psychiatric disorder with those with primary SUD; we also compared those with current versus past SUD., Results: In contrast to findings in other settings, there were no significant differences in the severity of psychopathology between patients with and without substance abuse/dependence. Within dually diagnosed patients, those with primary mental disorder were more anxious and depressed than those with primary SUD. Patients with primary mental disorder had a significantly higher number of psychiatric diagnoses, an earlier onset of any psychiatric disorder, and were more likely to have received treatment. Conversely, patients with primary SUD had a higher number of substance use disorder diagnoses and an earlier onset of SUD., Conclusion: Dually diagnosed patients had the same degree of psychopathology as patients with only psychiatric disorders in this outpatient psychiatric population. The primary/secondary classification may be useful to distinguish between subgroups of dual diagnosis patients. Future studies are necessary to determine if this distinction can be useful to predict course and outcome in dually diagnosed patients.

DSM-IV is provisionally including a category of mixed anxiety and depression for several reasons. First, it will be included in ICD-10, and therefore used worldwide. The ICD-10 category and the mixed anxiety and depression category now being included in the appendix of DSM-IV are subsyndromal in that they include patients with both anxious and depressive symptoms that fail to meet criteria for an established anxiety or depression diagnosis. Primary-care physicians regularly report a high incidence of patients whose symptoms fit this subsyndromal definition of mixed anxiety and depression. Such patients are not easily classifiable using DSM-III or DSM-III-R criteria, yet they often manifest sufficient distress and/or disability to require treatment. Those who oppose establishing the diagnosis of mixed anxiety and depression make the following points: (1) patients considered eligible for this diagnosis will actually meet criteria for a current DSM disorder; (2) mixed anxiety and depression will become a "wastebasket" category for a heterogeneous group of patients; (3) if any new subsyndromal diagnosis is needed, minor depression should suffice; and (4) mixed anxiety and depression will overlap extensively with adjustment reaction.

According to the official nomenclature and the approved indications for psychotropic drugs, anxiety and depression are mutually exclusive, and antidepressants and anxiolytics have a single indication. In clinical settings, however, anxiety and depressive symptoms frequently coexist, and the effects of psychotropic drugs often overlap. Both diagnosis and treatment may be complicated by uncertainty about the primary disorder and the optional therapeutic approach. Available treatment strategies include antidepressants, benzodiazepines, azapirones, and combined antidepressant/anxiolytic therapy. Considerations in reflecting a particular treatment strategy include drug side effects, patient age and medical status, and patient expectations. Recent studies have suggested that antidepressants are effective anxiolytics and that some anxiolytics produce antidepressant effects. Ultimately, any selection should be made based on relative benefits and risks of each approach.

Mixed anxiety and depression (MAD) is a new diagnostic category introduced in the ICD-10 classification for patients seen mainly in primary care settings. These patients are defined as those suffering from symptoms of anxiety and depression of limited and equal intensity accompanied by at least some autonomic features, who do not qualify for specific diagnosis of anxiety or depressive disorders and are independent of stressful life events. The validity of this clinical entity is presently under investigation in the DSM-IV-MAD field trial. Cases of mixed anxiety and depression, however, are not limited to those meeting the criteria of this new "subsyndromal" category. Many patients fulfilling criteria for either depressive or anxiety disorders may also respectively present symptoms, syndromes, or a diagnosis of anxiety or depression. It is still not known whether anxious and depressive symptoms are two different expressions of the same psychopathologic underlying process. Tyrer's recent description of a "general neurotic syndrome" is an attempt to reunify syndromes separated in our present classifications. In this comprehensive approach, anxiety, depression, or MAD states are associated at different times with specific personality features and considered as expressing different levels of overreactivity to various stressful situations. This hypothesis would explain the close relationship existing between these two categories of symptoms and the common efficacy of some psychopharmacologic agents for both anxiety and depressive disorders.

Recent epidemiologic studies (i.e., studies conducted since 1980) have consistently demonstrated, on the basis of standardized diagnostic assessments, that there is a substantial overlap between different types of anxiety and depressive disorders. The current literature, however, discusses this issue primarily within the concept of comorbidity and there are some controversies about the existence of a separate disorder of mixed anxiety-depression (MAD). MAD can be defined by the presence of mixed symptoms of depression and anxiety that are below the diagnostic threshold for either one of these diagnoses. Since MAD has not been included in any of the current official classification systems, its prevalence, risk factors, course, and outcome have not been studied specifically in any of the recent epidemiologic studies even though MAD is thought to be very important, especially in primary care settings. This paper reviews recent epidemiologic studies and presents data from the Munich Follow-Up Study, which has found a prevalence of about 1% for MAD as defined by the ICD-10. Despite the lack of clear diagnostic criteria for MAD, there are some indications that: (1) this disorder might be frequent in primary care settings, and (2) patients with MAD frequently demonstrate subjective suffering, show impairment in personal and occupational functioning, and have high health service utilization rates. Current empirical evidence is still insufficient for deciding a suitable classificatory solution for this problem.

Both primary care physicians and psychiatrists report frequent difficulty in distinguishing between major depression and generalized anxiety disorder. This fact has suggested the need for a new diagnostic category of mixed anxiety and depression. The solution, however, does not address the fundamental issues and creates additional problems. While there are multiple factors contributing to the difficulty in distinguishing between these categories, two are of paramount importance. First, pivotal cross-sectional criteria for the two disorders as enumerated in DSM-III-R are virtually identical. Second, the crux of the distinction between these two disorders involves factors other than the immediate cross-sectional presentation in the office such as the longitudinal course of the patient's complaints. Obtaining such a history takes time and training. For a variety of reasons (e.g., time allocated for patient evaluation, physician training), such a longitudinal history may not be elicited in a primary care office. To respond to these problems by establishing a mixed diagnostic category does not address the primary problems, may encourage cursory evaluations of patients, and will likely hinder research.

The problem of classifying mood disorders still lacks an acceptable solution. Interrater reliability studies have shown that this problem is more prevalent in mood disorders compared with other psychiatric conditions. Historically the problem originates from the distinction between Geisteskrankheiten and Gemütskrankheiten (mental and mood disorders) because the domain covered by the word mood has been progressively reduced. The fact that neurotic disorders are "emotional disorders" further complicates this field. The words anxiety and depression refer to a disorder, to a symptom, and to everyday feelings. A failure or difficulty in the distinction between these three meanings leads to nosological confusion. In recent years, the notion of a spectrum of mood disorders has gained acceptance. According to this, the diverse disorders are placed on a point that is more or less close to one of the extremes. Something similar occurs in the unipolar-bipolar distinction, in which the bipolar II or atypical and bipolar III occupy a central place on the spectrum. Cluster analysis and other mathematical techniques have helped to clarify the outlook, but there is a need for a biopsychosocial perspective and for a deeper understanding of the natural history of these disorders.

Clinical and research findings are reviewed in relation to the distinction between endogenous and exogenous anxiety. The single most potent discriminating symptom between the two subtypes is the presence or absence of spontaneous (anxiety) symptom attacks. This concept avoids the diagnostic difficulties that can arise under current systems when patients present with symptoms that fulfill the criteria for multiple anxiety-related diagnosis. Patients in the endogenous category differ from those whose anxiety is reactive in age of onset, clinical course, and response to psychotherapy and medication. Thus, this distinction appears to have clinical merit.

Approaches to the classification and treatment of anxiety have been lacking because of the unclear borders between pathologic and normal anxiety and the heterogeneity of patients called "anxious." The differentiation of panic from other anxiety states is a recent development in psychiatric nosology. The diagnosis of panic disorder and agoraphobia and their demarcation from other psychiatric and medical disorders are reviewed. Proposals to revise DSM-III criteria to provide concordance with current etiologic theories are discussed, and an overall treatment strategy that takes into account the multiple manifestations of the illness is outlined.

Studies of the treatment of panic anxiety and various other states with monoamine oxidase (MAO) inhibitors are critically reviewed. It is concluded that MAOIs have differential effects on several dimensions of pathologic anxiety. The association between depression and anxiety states is also reviewed; it is observed that MAOIs effectively treat severe anxiety and phobic disorders without operating strictly via their antidepressant mechanism. In addition, it is proposed that biologic depression and biologic anxiety should be considered to have some independence from one another. Guidelines for the clinical delineation of anxiety disorders are provided, and the clinical and research implications of the proposal for revision of DSM-III anxiety and phobic disorders section, are outlined in detail. It is suggested that anxiety and phobic disorders be classified into endogenous (disease) and exogenous (nondisease) types.