A meta-analysis of the influence of comorbidity on treatment outcome in the anxiety disorders

https://doi.org/10.1016/j.cpr.2010.04.008Get rights and content

Abstract

Although psychiatric comorbidity is common among patients with anxiety disorders, its impact on treatment outcome remains unclear. The present study used meta-analytic techniques to examine the relationship between diagnostic comorbidity and treatment outcome for patients with anxiety disorders. One hundred forty-eight anxiety-disordered treatment samples (combined N = 3534) were examined for post-treatment effects from the PsychINFO database. Samples consisted of those exposed to both active (CBT, dynamic therapy, drug treatment, CBT + drug treatment, mindfulness) and inactive treatments (placebo/attention control, wait-list). All treatments were associated with significant improvement at post-treatment, and active treatments were associated with greater effects than were inactive treatments. However, overall comorbidity was generally unrelated to effect size at post-treatment or at follow-up. A significant negative relationship between overall comorbidity and treatment outcome was found for mixed or “neurotic” anxiety samples when examining associations between comorbidity and specific diagnoses. Conversely, there was a significant positive relationship between overall comorbidity and treatment outcome for panic disorder and/or agoraphobia and PTSD or sexual abuse survivors. These findings suggest that while diagnostic comorbidity may not impact the effects of specific anxiety disorder treatments, it appears to differentially impact outcome for specific anxiety disorder diagnoses.

Introduction

Anxiety disorders are the most common category of psychiatric disorders, with a 12-month prevalence of 18% and a lifetime prevalence of 29% (Kessler et al., 2005, Kessler et al., 2005). Anxiety disorders also exert a substantial negative impact on quality of life (Olatunji, Cisler & Tolin, 2007). For example, there is evidence of marital and financial problems in patients with panic disorder (Weissman, 1991), impairment in education and relationships in patients with social phobia (Stein & Kean, 2000), high rates of public financial assistance and diminished subjective well-being in patients with post-traumatic stress disorder (PTSD; Zatzick et al., 1997), role limitations in patients with Obsessive–Compulsive Disorder (OCD; Hollander, Kwon, Stein & Broatch, 1996), and high rates of divorce and disability in patients with Generalized Anxiety Disorder (GAD; Blazer, Hughes, George, Swartz & Boyer, 1991). Quality of life is also lower among anxiety disorder patients with higher rates of comorbidity (Lochner et al., 2003).

Comorbidity in the anxiety disorders may result in greater psychopathology and more dysfunction (Coryell et al., 1988, Lecrubier, 1998) resulting in a lower quality of life. This is an important concern given that rates of comorbidity between anxiety and other mental disorders are substantial (Lewinsohn, Zinbarg, Seeley, Lewinsohn & Sack, 1997). For example, Sanderson, DiNardo, Rapee and Barlow (1990) found that 70% of anxiety patients received at least one additional Axis I diagnosis. More recent research has shown that 92% of those with a full DSM-IV diagnosis of GAD qualify for another lifetime DSM-IV disorder (Ruscio et al., 2007). Prior research has shown that anxiety disorders tend to be highly comorbid with mood, substance, and personality disorders (Brown & Barlow, 1992), and presence of specific patterns of comorbidity (e.g., personality disorders) has been shown to be associated with more severe pathology among patients with anxiety disorders (Dreessen, Arntz, Luttels & Sallaerts, 1994).

Comorbidity may also influence treatment outcome in the anxiety disorders (Brown and Barlow, 1992, Tsao et al., 2005). Although a large body of evidence from Randomized Controlled Trials (RCTs) supports the efficacy of CBT, concern has been raised about the utility of CBT, and other empirically-based treatments that are very specific and manual-driven, in the ‘real world’ (Westen, Novotny, & Thompson, 2004). Specificity and problem focused nature of CBT has been the basis of arguments that such a treatment may not generalize to real-life “patients” who are heterogeneous and frequently present with comorbid disorders. Consistent with this notion, research has shown that comorbidity is associated with higher anxiety disorder symptom levels after CBT (Ledley et al., 2005, Weertman et al., 2005). In fact, the negative impact of comorbid major depression on CBT outcome has prompted formulations of a treatment program specifically for depressed OCD patients (Abramowitz, 2004). However, other studies have shown that comorbidity does not significantly influence outcome during CBT for anxiety disorders (e.g., Brown, Anthony, & Barlow, 1995; Dreessen et al., 1997, Tsao et al., 2002, Ollendick et al).

The present meta-analysis aims to address inconsistent findings as to the relationship between psychiatric comorbidity and treatment outcome in the anxiety disorders. Accordingly, we selected treatment outcome studies and rated them for the proportion of patients diagnosed with comorbid conditions. A secondary aim is to examine whether impact of comorbidity on treatment outcome differs according to the type of treatment being provided. Several empirically supported treatments have been identified for the anxiety disorders (see Deacon & Abramowitz, 2004 for review), most of which achieve good outcomes through cognitive (cognitive restructuring) and behavioral (e.g., exposure) interventions. However, pharmacological agents (Mitte, Noack, Steil & Hautzinger, 2005) and psychodynamic therapy (Milrod, Leon, Busch, et al. 2007) also reduce symptoms of anxiety disorders. Although these different treatments have distinct active components, the extent to which they are differentially influenced by comorbidity is unclear. Recent research suggests that outcome for comorbid conditions may vary as a function of anxiety disorder diagnosis (Hofmann & Smits, 2008). Thus, the present meta-analysis also examined the extent to which treatment outcome for different anxiety disorder diagnosis are influenced by comorbidity.

Section snippets

Selection of studies

We identified appropriate studies by conducting searches in the PsychINFO database. We conducted searches using a journal title identifier (8 different search terms; Journal of Consulting and Clinical Psychology, American Journal of Psychiatry, Behavior Therapy, Behaviour Research and Therapy, Journal of the American Academy of Child and Adolescent Psychiatry, Journal of Abnormal Child Psychology, Journal of Clinical Child Psychology, and Development and Psychopathology),1

Discussion

Although anxiety disorders commonly have comorbid diagnosis (Barlow, DiNardo, Vermilyea, Vermilyea & Blanchard, 1986), it remains unclear if such comorbidity is associated with poorer outcomes. Some have questioned the extent to which published RCTs of psychotherapy can be generalized to community outpatients. For example, Westen and Morrison (2001) report that exclusion rates for RCTs for three common disorders were 68% for depression, 64% for panic, and 65% for GAD. The investigators further

Acknowledgement

We thank Steven D. Hollon for valuable comments on a previous draft of this article.

References (137)

  • P. *Carlbring et al.

    Treatment of panic disorder via the internet: a randomized trial of a self-help program

    Behavior Therapy

    (2001)
  • D.L. *Chambless

    Spacing of exposure sessions in treatment of agoraphobia and simple phobia

    Behavior Therapy

    (1990)
  • D.L. Chambless et al.

    MCMI-diagnosed personality disorders among agoraphobic outpatients: Prevalence and relationship to severity and treatment outcome

    Journal of Anxiety Disorders

    (1992)
  • J.A. *Cohen et al.

    A multisite, randomized controlled trial for children with sexual abuse-related PTSD symptoms

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2004)
  • J.A. *Cohen et al.

    A pilot randomized controlled trial of combined trauma-focused CBT and Setraline for childhood PTSD symptoms

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2007)
  • M.G. Craske et al.

    Cognitive behavioral therapy for panic disorder and comorbidity: More of the same or less of more

    Behaviour Research and Therapy

    (2007)
  • L. Dreessen et al.

    The impact of personality disorders on treatment outcome of anxiety disorders: Best-evidence synthesis

    Behaviour Research and Therapy

    (1998)
  • L. Dreessen et al.

    Personality disorders do not influence the results of cognitive behavior therapies for anxiety disorders

    Comprehensive Psychiatry

    (1994)
  • L. Dreessen et al.

    Personality disorders do not influence the results of cognitive and behavior therapy for obsessive compulsive disorder

    Journal of anxiety disorders

    (1997)
  • A. *Ehlers et al.

    Cognitive therapy for post-traumatic stress disorder: development and evaluation

    Behaviour Research and Therapy

    (2005)
  • D. *Heyne et al.

    Evaluation of child therapy and caregiver training in the treatment of school refusal

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2002)
  • T.M. *Keane et al.

    Implosive (flooding) therapy reduces symptoms of PTSD in Vietnam combat veterans

    Behavior Therapy

    (1989)
  • R.G. *Klein et al.

    Imipramine treatment of children with separation anxiety disorder

    Journal of the American Academy of Child and Adolescent Psychiatry

    (1992)
  • N.J. *King et al.

    Treating sexually abused children with posttraumatic stress symptoms: A randomized clinical trial

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2000)
  • D. *Koszycki et al.

    Randomized trial of a meditation-based stress reduction program and cognitive behavior therapy in generalized social anxiety disorder

    Behaviour Research and Therapy

    (2007)
  • P. Lewinsohn et al.

    Comorbidity between anxiety disorders and between anxiety disorders and other mental disorders in children

    Journal of Anxiety Disorders

    (1997)
  • K. *Manassis et al.

    Group and individual cognitive–behavioral therapy for childhood anxiety disorders: A randomized trial

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2002)
  • I.M. Marks et al.

    Brief standard self-rating for phobic patients

    Behaviour Research and Therapy

    (1979)
  • C. Masia-Warner et al.

    The Liebowitz Social Anxiety Scale for Children and Adolescents: An initial psychometric investigation

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2003)
  • R.P. Mattick et al.

    Development and validation of measures of social phobia scrutiny fear and social interaction anxiety

    Behaviour Research and Therapy

    (1998)
  • T.J. Meyer et al.

    Development and validation of the Penn State Worry Questionnaire

    Behaviour Research and Therapy

    (1990)
  • B.O. Olatunji et al.

    Quality of life in the anxiety disorders: A meta-analytic review

    Clinical Psychology Review

    (2007)
  • T.H. Ollendick

    Reliability and validity of the Revised Fear Survey Schedule for Children (FSSC-R)

    Behaviour Research and Therapy

    (1983)
  • T.H. Ollendick et al.

    Comorbidity as a predictor and moderator of treatment outcome in youth with anxiety, affective, attention deficit/hyperactivity disorder, and oppositional/conduct disorders

    Clinical Psychology Review

    (2008)
  • N. *Paunovic et al.

    Cognitive–behavior therapy vs exposure therapy in the treatment of PTSD in refugees

    Behaviour Research and Therapy

    (2001)
  • T.M. Achenbach

    Integrative guide for the 1991 CBCL14-18 YSR and TRF profiles

    (1991)
  • J.S. Abramowitz

    Treatment of obsessive–compulsive disorder in patients with comorbid major depression

    Journal of Clinical Psychology/In Session

    (2004)
  • L.B. Allen et al.

    Comorbidity as a moderator and outcome measure in patients receiving cognitive-behavioral treatment for panic disorder with agoraphobia

  • G. *Andersson et al.

    Internet-based self-help with therapist feedback and in vivo group exposure for social phobia: A randomized controlled trial

    Journal of Consulting and Clinical Psychology

    (2006)
  • D.H. Barlow

    Anxiety and its disorders: The nature and treatment of anxiety and panic

    (2002)
  • D.H. Barlow et al.

    Co-morbidity and depression among the anxiety disorders: Issues in diagnosis and classification

    Journal of Nervous and Mental Disease

    (1986)
  • C. *Barrowclough et al.

    A randomized trial of the effectiveness of cognitive–behavioral therapy and supportive counseling for anxiety symptoms in older adults

    Journal of Consulting and Clinical Psychology

    (2001)
  • A.T. Beck et al.

    An inventory for measuring clinical anxiety: Psychometric properties

    Journal of Consulting and Clinical Psychology

    (1988)
  • D.C. *Beidel et al.

    Behavioral treatment of childhood social phobia

    Journal of Consulting and Clinical Psychology

    (2000)
  • J. *Benjamin et al.

    Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder

    American Journal of Psychiatry

    (1995)
  • D.D. Blake et al.

    The development of a clinician-administered PTSD scale

    Journal of Traumatic Stress

    (1995)
  • D.G. Blazer et al.

    Generalized anxiety disorder

  • T.A. Brown

    Temporal course and structural relationships among dimensions of temperament and DSM-IV anxiety and mood disorder constructs

    Journal of Abnormal Psychology

    (2007)
  • T.A. Brown et al.

    Diagnostic comorbidity in panic disorder: Effect on treatment outcome and course of comorbid diagnoses following treatment

    Journal of Consulting and Clinical Psychology

    (1995)
  • T.A. Brown et al.

    Comorbidity among anxiety disorders: Implications for treatment and DSM-IV

    Journal of Consulting and Clinical Psychology

    (1992)
  • Cited by (0)

    Indicates studies used in the meta-analysis.

    View full text