Comorbidity of anxiety and depressive disorders: issues in conceptualization, assessment, and treatment

OBJECTIVES: The purpose of this review is to provide a clinically relevant analysis of issues concerning comorbidity among anxiety and depressive disorders. The co-occurrence of social anxiety disorder (SAD) and generalized anxiety disorder (GAD) with depressive disorders is highlighted as an illustration. Data on prevalence, rates of comorbidity, order of onset, course, and functional impairment associated with these disorders, in both the general population and clinical samples, are examined. The second half of the review focuses on discussion of practical issues concerning assessment and treatment of comorbid anxiety and depressive syndromes. CONCLUSIONS: Available evidence suggests that comorbidity among SAD, GAD, and the depressive disorders is substantial and pervasive. Co-occurrence of these syndromes is typically characterized by a chronic course with clinically significant impairment in social and occupational functioning. SAD and GAD precede the onset of major depression in a majority of cases and appear to be risk factors for developing major depression. Clinicians encountering patients with primary complaints of anxiety or depression should carefully assess for the presence of comorbid symptoms and syndromes. Treatment outcome research suggests that pharmacotherapy and psychosocial therapy (cognitive-behavior therapy in particular) both represent viable first-line treatment alternatives. However, with increasing severity of depression, pharmacotherapy is indicated as a primary intervention. The authors recommend increased efforts in screening and detection, more clinical trials that include patients with comorbid syndromes and symptoms, and continued research on the integration of pharmacological and psychotherapeutic treatments.     

Are anxiety and depression addressed in primary care patients with chronic obstructive pulmonary disease? A chart review

Objective: Screening for mental illness in primary care is widely recommended, but little is known about the evaluation, treatment, and long-term management processes that follow screening. The aim of this study was to examine and describe the quality of mental health care for persons with chronic obstructive pulmonary disease (COPD) and anxiety/depressive disorders, as measured by adherence to practice guidelines. Method: This retrospective chart review examined data for 102 primary care and mental health care patients with COPD who were diagnosed, using Structured Clinical Interview for DSM-IV criteria, with major depressive disorder, dysthymia, depression not otherwise specified, generalized anxiety disorder, or anxiety not otherwise specified. Data were gathered from primary care progress notes from the year prior to enrollment in a randomized controlled trial (enrollment was from July 2002 to April 2004). We compared the care received by these patients over 1 year with that recommended by practice guidelines. Charts were abstracted using a checklist of recommended practice guidelines for diagnostic evaluation, acute treatment, and long-term management of anxiety and depressive disorders. Results: Fifty (49%) of the 102 patients were recognized during the review year as having an anxiety or depressive disorder. Eighteen patients were newly assessed for depressive or anxiety disorders during the chart review year. Patients followed in primary care alone, compared with those who were comanaged by mental health care providers, were less likely to have guideline-adherent care. Conclusion: Depressive and anxiety disorders are recognized in about half of patients; however, guideline-supported diagnostic evaluation, acute treatment (except for medications), and long-term management rarely occur in the primary care setting. To improve the treatment of depressive and anxiety disorders in primary care, the process of care delivery must be understood and changed.     

Depressive, anxiety, and somatoform disorders in primary care: prevalence and recognition

Recent studies emphasize the negative impact of comorbidity on the course of depression. If undiagnosed, depression and comorbidity contribute to high medical utilization. We aimed to assess (1) prevalences of depression alone and with comorbidity (anxiety/somatoform disorders) in primary care, (2) coexistence of anxiety/somatoform disorders in depressive patients, and (3) diagnostic validity of two screeners regarding depression with versus without comorbidity. We examined 394 primary care outpatients using the Composite International Diagnostic Interview (CIDI), the General Health Questionnaire (GHQ-12), and the Well-Being Index (WHO-5). We conducted configurational frequency analyses to identify nonrandom configurations of the disorders and receiver operating characteristic (ROC)-analyses to assess diagnostic validity of the screeners. Point prevalence of any depressive disorder was 22.8%; with at least one comorbid disorder, 15%; and with two comorbid conditions, 6.1%, which significantly exceeded expected percentage (0.9%, P< or =.0001). Depression without comorbidity occurred significantly less often than expected by chance (P< or =.0007). Comorbidity of depressive and anxiety or somatoform disorders was associated with a high odds ratio (6.25). The screeners were comparable regarding their diagnostic validity for depression with [GHQ-12: area under the curve (AUC)=0.86; WHO-5: AUC=0.88] and without comorbidity (GHQ-12: AUC=0.84; WHO-5: AUC=0.86). It can be concluded that comorbidity between depression and anxiety/somatoform disorders in primary care may occur much more frequently than expected. These results confirm assumptions that the current division between depression and anxiety might be debatable. Validity of screeners tested in our study was not affected by comorbid conditions (e.g., anxiety or somatoform disorders).     

Depression: Diagnosis and Management for the Primary Care Physician

BACKGROUND: Much has been learned in recent years about the diagnosis and treatment of depression, a serious, commonly overlooked psychiatric illness often seen initially by the primary care physician. The objective of this article is to review the diagnosis and treatment of depression in primary care practice. METHOD: Relevant articles on depression were identified by a comprehensive MEDLINE search and classified into the following categories: diagnosis and screening, nonpharmacologic therapy, pharmacologic therapy, newer antidepressant agents, and maximizing antidepressant therapy. The importance to primary care practice was considered in determining the significance of each article reviewed. RESULTS: Because no laboratory tests exist for depression and no biological markers can be measured routinely, the diagnosis of depression must be made with a number of reliable depression scales and questionnaires that can be completed quickly in the primary care setting. The considerable overlap between depressive and anxiety disorders further complicates an accurate diagnosis. Remission (i.e., absence of symptoms) is the ultimate goal of therapy for patients who have depressive symptoms. CONCLUSION: Many patients can be treated safely and effectively for depression in the primary care setting with pharmacologic therapy, which, if completely successful, can lead to full remission of the disorder.     

Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders

OBJECTIVE: Attention deficit hyperactivity disorder is a heterogeneous disorder of unknown etiology. Little is known about the comorbidity of this disorder with disorders other than conduct. Therefore, the authors made a systematic search of the psychiatric and psychological literature for empirical studies dealing with the comorbidity of attention deficit hyperactivity disorder with other disorders. DATA COLLECTION: The search terms included hyperactivity, hyperkinesis, attention deficit disorder, and attention deficit hyperactivity disorder, cross-referenced with antisocial disorder (aggression, conduct disorder, antisocial disorder), depression (depression, mania, depressive disorder, bipolar), anxiety (anxiety disorder, anxiety), learning problems (learning, learning disability, academic achievement), substance abuse (alcoholism, drug abuse), mental retardation, and Tourette's disorder. FINDINGS: The literature supports considerable comorbidity of attention deficit hyperactivity disorder with conduct disorder, oppositional defiant disorder, mood disorders, anxiety disorders, learning disabilities, and other disorders, such as mental retardation, Tourette's syndrome, and borderline personality disorder. CONCLUSIONS: Subgroups of children with attention deficit hyperactivity disorder might be delineated on the basis of the disorder's comorbidity with other disorders. These subgroups may have differing risk factors, clinical courses, and pharmacological responses. Thus, their proper identification may lead to refinements in preventive and treatment strategies. Investigation of these issues should help to clarify the etiology, course, and outcome of attention deficit hyperactivity disorder.     

Psychiatric and Medical Comorbidity in the Primary Care Geriatric Patient—An Update

The mental health needs of older primary care patients are now widely recognized if not widely addressed. The range of behavioral health approaches including co-locating psychiatrists and integrating mental health professionals as care managers into primary care sites is extensive and growing. Nonetheless the primary care provider remains the first line of defense against mental disorders, most commonly depression and anxiety that accompany and exacerbate common physical conditions. The excess, potentially avoidable disability that results from comorbidity makes it imperative that early recognition and evidence based intervention occur. Multi-morbidity and polypharmacy make intervention a challenge. Psychotherapy can help overcome comorbidity depression however the most accessible intervention would be an antidepressant FDA approved for both anxiety and depressive disorders. For all these reasons, a focus on physical conditions most commonly associated with mental disorders can foster early recognition before the older patient’s care becomes overwhelmingly complicated.     

Comorbidity of depressive disorders among adolescents in community and clinical settings

The aim of this article was to examine the comorbidity rates and clinical characteristics of depressive disorders among adolescents in community and clinical settings, using the same methodology. One thousand and thirty-five adolescents from the community setting and 200 adolescents from the clinical setting were interviewed using the computerized Munich version of the Composite International Diagnostic Interview. In both settings, the comorbidity of depressive disorders with other psychiatric disorders was high. About 58% of the depressed adolescents in the community setting had at least one additional disorder, compared with 63.5% in the clinical setting. The most common comorbid pattern was that of depressive and anxiety disorders. Among adolescents with anxiety and depression, 72% and 62% of those in the community and clinical settings, respectively, reported the occurrence of anxiety before that of depression. Depressed adolescents with comorbid disorders used significantly more mental health services than adolescents with depression only. The findings suggest the need to design assessment and intervention strategies to deal with adolescents with multiple disorders.     

Prevalence and determinants of depressive disorders in primary care practice in Spain

OBJECTIVE: Depressive disorders are considered to be a public health problem. Primary health care plays an important role in the treatment of such disorders. Our aim is to determine the prevalence and determinant factors of major depression and dysthymia in consecutive primary care attenders. METHOD: The study took place in medical consultations in 10 Primary Care Centers in Tarragona (Spain). It was designed as a two-phase cross-sectional study. In the first phase we screened 906 consecutive patients according to Zung's Self-Rating Depression Scale. In the second phase the 209 patients whose results were positive and 97 patients whose results were negative (1/7 chosen at random) were given the Structured Clinical Interview for DSM-IV Axis I Disorders, plus a series of questionnaires. We evaluated the link between major depression and dysthymia and several sociodemographic and clinical variables using non-conditional logistic regression. RESULTS: Weighted prevalence was 14.3% (CI 95%: 11.2-17.4) for major depression and 4.8% (CI 95%: 2.8-6.8) for dysthymia. Independently linked to the presence of major depression were female sex, panic disorder, generalized anxiety disorder, frequency of primary care visits, and clinical presentation in the form of explicitly psychosocial symptoms as opposed to exclusively somatic symptoms. Independently linked to the presence of dysthymia were age, generalized anxiety disorder and psychosocial symptoms. CONCLUSION: In our area, depressive disorders in primary care attenders are very common. General practitioners should be aware of this fact so that these disorders can be detected and treated correctly.     

Use of algorithms to treat anxiety in primary care

The presentations of anxiety in primary care are more numerous and broader in spectrum than the presentations of depression, and the primary care physician is often faced with the challenge of teasing out a diagnosis from the full spectrum of anxiety disorders. A treatment algorithm that begins with recognition and diagnosis and carries the primary care physician and patient through long-term treatment and, finally, withdrawal of treatment can be a useful and appropriate tool. Use of an algorithm targeted specifically for primary care physicians treating patients with anxiety disorders would insure that patients in the primary care setting receive the best care during treatment of anxiety disorders, while primary care physicians become better able to serve a broader community.     

Anxiety disorders and comorbid depression in community dwelling older adults

Anxiety disorder is a common psychiatric problem during late‐life, and frequently co‐occurs with depression. High comorbidity between anxiety and depression may partly be explained by the definition of the disorders and the assessment of both disorders with one instrument at the same time. The current study investigates the relation of current and past depression with anxiety disorders in the Rotterdam Study, a large population‐based cohort study of older adults in the Netherlands (n study population = 5565). DSM‐IV anxiety disorder was ascertained with the Munich version of the Composite International Diagnostic Interview. DSM‐IV depression was diagnosed with the Schedules for Clinical Assessment of Neuropsychiatry (SCAN) on a different day. Past depression was assessed from general practitioners' records, self‐report, and a prior SCAN interview. Of the 457 persons with an anxiety disorder, 11.6% had a comorbid major depression, and another 6.3% had other depressive syndromes. However, 49.3% of persons with an anxiety disorder experienced or had in the past experienced a depressive episode. Our study suggests that comorbid depression in older adults with anxiety disorders may be less prevalent than previously suggested. However, the relation of current anxiety disorders with past depression is substantial. Copyright © 2011 John Wiley & Sons, Ltd.     

Generalized anxiety disorder – a risk factor for depression?

Recent longitudinal epidemiological studies suggest that anxiety disorders usually precede the onset of depressive disorders and might be regarded as risk factors for secondary depressive disorders. This paper reviews the available evidence, which suggests that generalized anxiety disorder (GAD) is a temporally primary anxiety disorder, preceding the onset of depression. In retrospective studies, like other anxiety disorders, GAD in adulthood and among adolescents has been reported to precede the onset of depressive disorders in the majority of cases. Prospective longitudinal data suggest that GAD is associated with an increased risk of an earlier first onset of depression. Comparisons with panic disorder reveal that GAD cases predominantly develop depression after 2–4 years, whereas the majority of cases of panic disorder develop depression within a year after onset. These observations suggest differences in the pathogenesis of both conditions, which require further investigation. The comorbidity between GAD and major depression and the fact that temporally primary GAD significantly predicts a subsequent onset of depression raise the question of whether early intervention and treatment of primary GAD would effectively prevent the subsequent first onset of depression. Copyright © 2001 Whurr Publishers Ltd.     

Comparing primary and secondary generalized anxiety disorder in a long-term naturalistic study of anxiety disorders.

This study explores the potential differences in comorbidity and course between primary generalized anxiety disorder (GAD), which develops before other anxiety disorders, and secondary GAD. As part of the Harvard/Brown Anxiety Research Project (HARP), a naturalistic, long-term, longitudinal study of 711 subjects from a variety of clinic settings with DSM III-R defined anxiety disorders, 210 subjects with GAD were identified. Of these, 78 (37%) had primary GAD, and 84 (40%) had secondary GAD; of the remainder, 28 (13%) had no other anxiety disorder and 20 (10%) developed GAD within a month of another anxiety disorder and were excluded from the analysis. All subjects were comorbid for at least one other anxiety disorder. Primary GAD subjects were more likely to be in episode at intake (90% vs. 77%, P = .04) and less likely than secondary GAD subjects to have current or past agoraphobia without panic disorder (3% vs. 11%, P = .04), social phobia (19% v. 52%, P = .001), simple phobia (14% v. 30%, P = .02), or post traumatic stress disorder (5% vs. 20%, P = .01). Subjects with primary GAD were also less likely to have current or past alcohol use disorders (17% vs. 37%, P = .004) or major depressive disorder (60% vs. 76%, P = .03). There were no significant differences in either treatment approaches or remission rates for primary compared to secondary GAD. Whether GAD first occurs before or after another anxiety disorder, it is similar in terms of prevalence, treatment, and course. The only significant differences between primary and secondary GAD lie in the rates of comorbidity of both other anxiety disorders and non-anxiety disorders, including major depression and substance abuse. These results support the concept of GAD as a valid, separate and distinct entity, whether it occurs primarily or secondarily.     

The association of depression and anxiety with medical symptom burden in patients with chronic medical illness

BACKGROUND: Primary care patients with anxiety and depression often describe multiple physical symptoms, but no systematic review has studied the effect of anxiety and depressive comorbidity in patients with chronic medical illnesses. METHODS: MEDLINE databases were searched from 1966 through 2006 using the combined search terms diabetes, coronary artery disease (CAD), congestive heart failure (CHF), asthma, COPD, osteoarthritis (OA), rheumatoid arthritis (RA), with depression, anxiety and symptoms. Cross-sectional and longitudinal studies with >100 patients were included as were all randomized controlled trials that measure the impact of improving anxiety and depressive symptoms on medical symptom outcomes. RESULTS: Thirty-one studies involving 16,922 patients met our inclusion criteria. Patients with chronic medical illness and comorbid depression or anxiety compared to those with chronic medical illness alone reported significantly higher numbers of medical symptoms when controlling for severity of medical disorder. Across the four categories of common medical disorders examined (diabetes, pulmonary disease, heart disease, arthritis), somatic symptoms were at least as strongly associated with depression and anxiety as were objective physiologic measures. Two treatment studies also showed that improvement in depression outcome was associated with decreased somatic symptoms without improvement in physiologic measures. CONCLUSIONS: Accurate diagnosis of comorbid depressive and anxiety disorders in patients with chronic medical illness is essential in understanding the cause and in optimizing the management of somatic symptom burden.     

Differences between detected and undetected patients in primary care and depressed psychiatric patients

The aim of this study was to explore differences between primary care and tertiary psychiatry patients meeting DSM-III-R criteria for depressive disorders in terms of a wide range of demographic and clinical variables including psychiatric comorbidity. A weighted sample of 153 depressed primary care patients was obtained from the waiting rooms of family physicians using a two-stage selection and assessment procedure including the Structured Clinical Interview for the DSM-III-R (SCID). A measure of physician detection was also obtained. The 123 depressed psychiatric patients were seeking evaluation and treatment at a university-based depression program, and DSM-III-R diagnoses were also obtained using the SCID. Overall, fewer depressed primary care patients met criteria for major depressive disorder, and more of those who did were only mildly depressed. Depressed primary care patients were more likely to be women, older, and had less education, less past treatment, and greater lifetime comorbidity. Clinical differences were greatest for the depressed patients who had gone undetected by their physicians: they were higher functioning, less distressed, and more mildly depressed. Findings are discussed in terms of the validity and acceptability of practice guidelines for depression in primary care.     

Depression and epilepsy, pain and psychogenic non-epileptic seizures: clinical and therapeutic perspectives

The clinical manifestations of depression in people with epilepsy (PWE) are pleomorphic, often associated with anxiety symptoms and anxiety disorders. The ongoing debate of whether the clinical presentation of depression in PWE is unique to this neurologic disorder is reviewed. Comorbid depression can impact the recruitment of PWE for pharmacologic trials with antiepileptic drugs (AEDs). Yet, the impact of depression on the response of the seizure disorder to pharmacotherapy with AEDs and its impact on worse adverse events may bias the interpretation of the trial findings, particularly when depressed patients are included in the AED trials. PWE have a greater suicidal risk than the general population. This risk is mediated by multiple factors, and recent data from the FDA have imputed a potential pathogenic role to all AEDs. The recognition of patients at risk is reviewed. Yet, the validity of the FDA data has been questioned, and the status of this controversial question is analyzed. As in the case of epilepsy, depression and pain syndromes have a relatively high comorbidity. The negative impact of depression on pain is reminiscent of that of depression in PWE; furthermore, the high comorbidity may be also associated with the existence of common pathogenic mechanisms. Neurologists and in particular, epileptologists establish the diagnosis of psychogenic non-epileptic seizures (PNES) in whom a comorbid depressive disorder is very often identified. The role of depression in the course of PNES and its treatment are discussed. Scarce data are available on the treatment of depression in PWE. Thus, clinicians have had to adopt data from patients with primary depressive disorders. We outline a consensus strategy on the identification and treatment of depressive disorders in adult and pediatric patients with epilepsy.     

Advances in the treatment of depression in older adults

Depressive symptoms in older adults are common, but the minority of elderly meet criteria for major depressive disorder. This has led to confusion regarding the recognition of diagnosis, approach to treatment, and monitoring of outcomes in this needy population. Few depressed older adults are willing to seek treatment from psychiatrists or mental health specialists. Treatment approaches to the depressive spectrum of disorders in late life, which encompasses major and minor depressive disorder, dysthymic disorder, and mood disorders related to medical conditions, must include evidence-based algorithms that can be delivered in a variety of health care settings. Several recent multisite trials have advanced the use of collaborative care models and the systematic stepwise approach to the treatment of depression and anxiety states in older adults. This offers the ability to provide effective treatment of depression for older adults, consistent with current guidelines, in primary care and specialized health care settings.     

Comparing anxiety disorders and anxiety-related traits in bipolar disorder and unipolar depression

The frequent comorbidity of anxiety disorders and mood disorders has been documented in previous studies. However, it remains unclear whether specific anxiety traits or disorders are more closely associated with unipolar major depression (MDD) or bipolar disorder (BPD). We sought to examine whether MDD and BPD can be distinguished by their association with specific types of anxiety comorbidity. Individuals with a primary lifetime diagnosis of either bipolar disorder (N=122) or major depressive disorder (N=114) received diagnostic assessments of anxiety disorder comorbidity, and completed questionnaires assessing anxiety sensitivity and neuroticism. The differential association of these anxiety phenotypes with MDD versus BPD was examined with multivariate modeling. Panic disorder and generalized anxiety disorder (GAD) specifically emerged amongst all the anxiety disorders as significantly more common in patients with BPD than MDD. After controlling for current mood state, anxiety sensitivity and neuroticism did not differ by mood disorder type. This study supports prior research suggesting a specific panic disorder-bipolar disorder connection, and suggests GAD may also be differentially associated with BPD. Further research is needed to clarify the etiologic basis of anxiety disorder/BPD comorbidity and to optimize treatment strategies for patients with these co-occurring disorders.     

Anxiety disorder comobidity in Bipolar I Disorder: relationship to depression severity and treatment outcome

The present study investigated the greater symptom severity and poorer treatment response found in patients with bipolar illness and anxiety comorbidity, and examined depression as a potential mediator of this relationship. The sample consisted of 92 patients in an acute episode of Bipolar I Disorder with a current or past history of an anxiety disorder. Diagnoses were based on structured clinical interview, and participants were assessed at pre-treatment and then randomly assigned to pharmacotherapy alone or pharmacotherapy plus family intervention. Patients were assessed on a monthly basis by blind assessors over 28 months. Compared to patients without anxiety comorbidity, individuals with bipolar disorder and an anxiety disorder possessed greater current symptom severity, even after controlling for depression severity. Logistic regression analysis identified that being female and having higher current depression but not manic severity predicted comorbid anxiety. Comorbid anxiety was associated with poorer treatment response in the sample regardless of treatment type, particularly in subsequent depressive symptoms. Multiple regression analyses indicated that current depression but not manic severity partially mediated the relationship between comorbid anxiety and treatment outcome. Results from the current study investigating comorbid anxiety disorders are consistent with past research limited to anxiety symptoms. Depression only partially accounted for the link between comorbid anxiety and greater symptom severity and poorer treatment response, and examination of other factors is warranted. Because of the clinical relevance of comorbid anxiety in severe affective disorders, treatments designed to specifically address both concerns are needed.     

Screening and Treating Mental Disorders in Addiction Treatment Settings: A Stepped Care Model

The comorbidity of mental and addiction disorders is increasingly apparent. Such comorbidity increases overall client morbidity substantially, and reduces the success rate in treating either type of disorder. In addiction treatment settings, the challenge is twofold: first, to develop a method for detecting mental disorders that is valid and practical, and second, to identify treatment approaches that are appropriate to that setting. Simple referral away of the patient with a mental disorder is rarely successful. Difficulties often arise in finding appropriate mental health treatments in a timely fashion; furthermore client resistance to being referred out poses an additional barrier. This article identifies strategies to improve practical detection of mental health disorders through the use of simple but validated patient self-reports. In addition, this commentary proposes a stepped care approach to the provision of mental health treatments that allows for some universally effective ‘wellness treatments’ to be initiated for all individuals in addiction treatment settings; those with persistent high psychiatric symptoms related to the most common disorders such as depression or anxiety would then receive some additional mental health treatment in the addiction setting. Referral out would be reserved for those individuals with more severe psychiatric illnesses or those with comparatively rarer disorders. This pragmatic approach to screening and stepped care increases the likelihood of success in treating the addictive disorder, as well as providing care for the mental disorder.