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.

[1]  G. H. Savage Constant Watching of Suicidal Cases , 1884 .

[2]  A R Feinstein,et al.  THE PRE-THERAPEUTIC CLASSIFICATION OF CO-MORBIDITY IN CHRONIC DISEASE. , 1970, Journal of chronic diseases.

[3]  G. Winokur,et al.  Depressed women with panic attacks. , 1984, The Journal of clinical psychiatry.

[4]  R. Noyes,et al.  Generalized anxiety disorder. , 1987, Primary care.

[5]  N. Andreasen,et al.  Depression and panic attacks: the significance of overlap as reflected in follow-up and family study data. , 1988, The American journal of psychiatry.

[6]  A. Stewart,et al.  The functioning and well-being of depressed patients. Results from the Medical Outcomes Study. , 1989, JAMA.

[7]  M. Stein,et al.  Major depression in patients with social phobia. , 1990, The American journal of psychiatry.

[8]  Syndrome comorbidity in patients diagnosed with a DSM-III-R anxiety disorder. , 1990, Journal of abnormal psychology.

[9]  R. Noyes,et al.  Examination of comorbid anxiety in psychiatric inpatients. , 1991, Comprehensive psychiatry.

[10]  G. Styan,et al.  Relationship of social phobia with other psychiatric illness. , 1991, Journal of affective disorders.

[11]  G Lewis,et al.  Measuring psychiatric disorder in the community: a standardized assessment for use by lay interviewers , 1992, Psychological Medicine.

[12]  T. Brown,et al.  Comorbidity among anxiety disorders: implications for treatment and DSM-IV. , 1992, Journal of consulting and clinical psychology.

[13]  M. Weissman,et al.  Social Phobia: Comorbidity and Morbidity in an Epidemiologic Sample , 1992 .

[14]  J. Cohn,et al.  Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies. , 1992, Neuropsychobiology.

[15]  M C Neale,et al.  Major depression and generalized anxiety disorder. Same genes, (partly) different environments? , 1992, Archives of general psychiatry.

[16]  J. Davidson,et al.  The epidemiology of social phobia: findings from the Duke Epidemiological Catchment Area Study , 1993, Psychological Medicine.

[17]  R. Shelton Pharmacotherapy of panic disorder. , 1993, Hospital & community psychiatry.

[18]  J. Ballenger,et al.  Psychiatric comorbidity in patients with generalized anxiety disorder. , 1993, The American journal of psychiatry.

[19]  D. Klein,et al.  Psychiatric disorders: Problems of boundaries and comorbidity. , 1993 .

[20]  J. Davidson,et al.  Treatment of social phobia with clonazepam and placebo. , 1993, Journal of clinical psychopharmacology.

[21]  D. Klein,et al.  A direct interview family study of social phobia. , 1993, Archives of general psychiatry.

[22]  R. Kessler,et al.  Major depression and phobias: the genetic and environmental sources of comorbidity , 1993, Psychological Medicine.

[23]  M. Keller,et al.  Quality of life and psychiatric morbidity in panic disorder and generalized anxiety disorder. , 1993, The American journal of psychiatry.

[24]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[25]  J. Lau,et al.  The Shatin community mental health survey in Hong Kong. II. Major findings. , 1993, Archives of general psychiatry.

[26]  E. Líndal,et al.  The lifetime prevalence of anxiety disorders in Iceland as estimated by the US National Institute of Mental Health Diagnostic Interview Schedule , 1993, Acta psychiatrica Scandinavica.

[27]  D. Chambless,et al.  Cognitive therapy of anxiety disorders. , 1993, Journal of consulting and clinical psychology.

[28]  R. Kessler,et al.  DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. , 1994, Archives of general psychiatry.

[29]  M. Liebowitz,et al.  Functional impairment in social phobia. , 1994, The Journal of clinical psychiatry.

[30]  R. Kessler,et al.  Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. , 1994, Archives of general psychiatry.

[31]  R. Bland,et al.  Life events and the 1-year prevalence of major depressive episode, generalized anxiety disorder, and panic disorder in a community sample. , 1994, Comprehensive psychiatry.

[32]  A. Rush,et al.  A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. , 1994, Archives of general psychiatry.

[33]  R. Noyes,et al.  Panic disorder: treatment with valproate. , 1994, The Journal of clinical psychiatry.

[34]  K. Kendler,et al.  A twin study of generalized anxiety disorder and major depression , 1995, Psychological Medicine.

[35]  D F Klein,et al.  Generalized social phobia. Reliability and validity. , 1995, Archives of general psychiatry.

[36]  A. Szegedi,et al.  Combination treatment with clomipramine and fluvoxamine: drug monitoring, safety, and tolerability data. , 1996, The Journal of clinical psychiatry.

[37]  R. Lydiard,et al.  Generalized anxiety disorder: issues in epidemiology. , 1996, The Journal of clinical psychiatry.

[38]  P. Roy-Byrne Generalized anxiety and mixed anxiety-depression: association with disability and health care utilization. , 1996, The Journal of clinical psychiatry.

[39]  R. Kessler,et al.  Comorbidity of DSM–III–R Major Depressive Disorder in the General Population: Results from the US National Comorbidity Survey , 1996, British Journal of Psychiatry.

[40]  P. Houck,et al.  Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. , 1996, The American journal of psychiatry.

[41]  K. Kendler Major Depression and Generalised Anxiety Disorder , 1996, British Journal of Psychiatry.

[42]  H. Wittchen,et al.  The impact of social phobia on quality of life , 1996, International clinical psychopharmacology.

[43]  M. Fava,et al.  Major depressive subtypes and treatment response , 1997, Biological Psychiatry.

[44]  C. R. Glass,et al.  Predictors of response to cognitive-behavioral group therapy for social phobia. , 1997, Journal of anxiety disorders.

[45]  M. Pollack,et al.  Cognitive behavioral and pharmacological treatment of generalized anxiety disorder: A preliminary meta-analysis , 1997 .

[46]  S. Montgomery,et al.  Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia. , 1997, Journal of affective disorders.

[47]  A. Beekman,et al.  Anxiety disorders in later life: a report from the longitudinal aging study Amsterdam , 1998, International journal of geriatric psychiatry.

[48]  P. Tyrer,et al.  Systematic review of the outcome of anxiety and depressive disorders , 1998, British Journal of Psychiatry.

[49]  D. Klein,et al.  Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome. , 1998, Archives of general psychiatry.

[50]  T. C. Bond,et al.  McLean Hospital Depression Research Facility: early-onset phobic disorders and adult-onset major depression , 1998, British Journal of Psychiatry.

[51]  M. Stein,et al.  Social phobia in the primary care medical setting. , 1999, The Journal of family practice.

[52]  J. Ballenger Clinical guidelines for establishing remission in patients with depression and anxiety. , 1999, The Journal of clinical psychiatry.

[53]  J. Davidson,et al.  Treatment of social phobia with gabapentin: a placebo-controlled study. , 1999, Journal of clinical psychopharmacology.

[54]  P. Mitchell,et al.  The influence of anxiety as a risk to early onset major depression. , 1999, Journal of affective disorders.

[55]  H. Akiskal,et al.  Depressive comorbidity of panic, social phobic, and obsessive-compulsive disorders re-examined: is there a bipolar II connection? , 1999, Journal of psychiatric research.

[56]  J. Davidson,et al.  A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder , 1999, Biological Psychiatry.

[57]  P. Sullivan,et al.  Gender differences in the rate of comorbid axis I disorders in depressed outpatients , 1999, Depression and anxiety.

[58]  Dan J Stein,et al.  Social Anxiety Disorder , 1999, CNS Spectrums.

[59]  R. Kessler,et al.  Lifetime co-morbidities between social phobia and mood disorders in the US National Comorbidity Survey , 1999, Psychological Medicine.

[60]  David H. Barlow,et al.  Cognitive-Behavioral Therapy, Imipramine, or Their Combination for Panic Disorder , 2020, The Neurotic Paradox.

[61]  J. Markowitz,et al.  A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. , 2000, The New England journal of medicine.

[62]  S. Pallanti,et al.  Social Anxiety and Premorbid Personality Disorders in Paranoid Schizophrenic Patients Treated With Clozapine , 2000, CNS Spectrums.

[63]  M. Fava,et al.  Anxiety disorders in major depression. , 2000, Comprehensive psychiatry.

[64]  M K Shear,et al.  Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. , 2000, JAMA.

[65]  K. Bucholz,et al.  Social phobia in a population-based female adolescent twin sample: co-morbidity and associated suicide-related symptoms , 2000, Psychological Medicine.

[66]  J. Davidson,et al.  Impact of generalized social anxiety disorder in managed care. , 2001, The American journal of psychiatry.

[67]  F. Schneier Treatment of social phobia with antidepressants. , 2001, The Journal of clinical psychiatry.

[68]  A. Metz,et al.  Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients? , 2001, The Journal of clinical psychiatry.

[69]  R. Judge,et al.  Patient perspectives on once-weekly fluoxetine. , 2001, The Journal of clinical psychiatry.

[70]  Essential Components of Cognitive-Behavior Therapy for Depression , 2000, Journal of Cognitive Psychotherapy.

[71]  M. Höfler,et al.  Social anxiety disorder and the risk of depression: a prospective community study of adolescents and young adults. , 2001, Archives of general psychiatry.

[72]  A. M. Ruscio,et al.  Psychotherapy for generalized anxiety disorder. , 2001, The Journal of clinical psychiatry.

[73]  J. Davidson,et al.  Efficacy of olanzapine in social anxiety disorder: a pilot study , 2002, Journal of psychopharmacology.

[74]  M. Fava,et al.  Fluoxetine treatment of depressed patients with comorbid anxiety disorders , 2002, Journal of psychopharmacology.

[75]  A. Pincus,et al.  A component analysis of cognitive-behavioral therapy for generalized anxiety disorder and the role of interpersonal problems. , 2002, Journal of consulting and clinical psychology.

[76]  M. Otto,et al.  Treating Medication-Resistant Panic Disorder: Predictors and Outcome of Cognitive-Behavior Therapy in a Brazilian Public Hospital , 2002, Psychotherapy and Psychosomatics.

[77]  Olga V. Demler,et al.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). , 2003, JAMA.

[78]  N. Simon,et al.  Combined Paroxetine and Clonazepam Treatment Strategies Compared to Paroxetine Monotherapy for Panic Disorder , 2003, Journal of psychopharmacology.

[79]  U. Lepola,et al.  Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder. , 2003, The Journal of clinical psychiatry.

[80]  M. Liebowitz,et al.  Citalopram treatment of social anxiety disorder with comorbid major depression , 2003, Depression and anxiety.

[81]  C. Lejuez,et al.  Contemporary behavioral activation treatments for depression: procedures, principles, and progress. , 2003, Clinical psychology review.

[82]  G. Keitner,et al.  Combined Psychotherapy and Pharmacotherapy for the Treatment of Major Depressive Disorder , 2004 .

[83]  D. Storch Generalized Anxiety Disorder: Advances in Research and Practice , 2005 .