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

Clinical Psychology Review 30 (2010) 642–654

Contents lists available at ScienceDirect

Clinical Psychology Review

A meta-analysis of the influence of comorbidity on treatment outcome in the anxiety disorders Bunmi O. Olatunji a,⁎, Josh M. Cisler b, David F. Tolin c a b c

Department of Psychology, Vanderbilt University, 301 Wilson Hall, 111 21st Avenue South, Nashville, TN 37203, USA University of Arkansas, USA The Institute of Living and Yale University, USA

a r t i c l e

i n f o

Article history: Received 5 October 2009 Received in revised form 7 April 2010 Accepted 20 April 2010 Keywords: Anxiety disorders Comorbidity Treatment Meta-analysis

a b s t r a c t 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. © 2010 Elsevier Ltd. All rights reserved.

Contents 1. 2.

Introduction . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . 2.1. Selection of studies . . . . . . . . . 2.2. Diagnosis and assessment of treatment 2.3. Operationalizing comorbidity . . . . . 2.4. Sample description. . . . . . . . . . 2.5. Analysis of treatment effects . . . . . 2.5.1. Intervention specificity . . . 2.5.2. Disorder specificity . . . . . 2.6. Analysis of comorbidity effects . . . . 2.6.1. Intervention specificity . . . 2.6.2. Disorder specificity . . . . . 3. Discussion . . . . . . . . . . . . . . . . . Acknowledgement . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

⁎ Corresponding author. E-mail address: [email protected] (B.O. Olatunji). 0272-7358/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.cpr.2010.04.008

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1. 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, Chiu, Demler & Walters, 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 & Barlow, 1992; Tsao, Mystkowski, Zucker & Craske, 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, Arntz, Schouten & Dreessen, 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, Hoekstra & Arntz, 1997; Tsao, Mystkowski, Zucker & Craske, 2002; Ollendick, Jarrett, GrillsTaquechel, Hovey & Wolff, 2008). 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.

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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. 2. Methods 2.1. 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 anxious population identifier (6 different search terms; ‘anxiety,’ ‘obsessive,’ ‘post-traumatic,’ ‘generalized,’ ‘phobia,’ and ‘panic’), and randomization identifier (2 different search terms; ‘random,’ and ‘randomized’). We placed no limits on the searches (e.g., search terms were not limited to the article titles). We conducted searches using all combinations of these identifier classes, resulting in 96 total PychINFO searches. These searches identified 276 total articles, and 224 unique articles (i.e., articles that did not appear in multiple searches). Articles were included if they met the following criteria (see Fig. 1): 1) report original results (i.e., not a literature review; not results from a previously published study), 2) conducted a clinical trial, 3) randomly assigned participants to treatment conditions, 4) conducted a pretreatment assessment using an objective assessment instrument, 5) reported relevant statistics for calculating effect sizes in the journal article,2 and 6) used a sample diagnosed with a primary or co-primary anxiety disorder. Sixty-one articles met all of these criteria and were included in the present study (see Table 1 for description of studies). 2.2. Diagnosis and assessment of treatment outcome Diagnostic inventories employed in the studies included the Structured Clinical Interview for the DSM–IV (n = 21; First, Spitzer, Gibbon & Williams, 1995), Anxiety Disorders Interview Schedule (n = 18; Brown, DiNardo & Barlow, 1994), CAPS (n = 6; Blake et al., 1995), Schedule for Affective Disorders and Schizophrenia (n = 3; Kaufman, Birmaher, Brent, Rao & Ryan, 1996), Composite International Diagnostic Interview (n = 3; World Health Organization, 1997), Yale-Brown Obsessive Compulsive Scale (n = 1), Diagnostic Interview for Children and Adolescents-revised (n = 3; Reich, 2000), Impact of Events Scale (n = 1), Mini International Neuropsychiatric Interview (n = 1; Sheehan et al., 1998), Fear Inventory (n = 1; Wolpe & Lazarus, 1966), Post-traumatic Stress Scale (n = 1; Reed & Enright, 2006), and two studies used unspecified structured interviews. Treatment outcome measures included the ADIS (n = 1; Brown et al., 1994), Agoraphobic Cognition Questionnaire (Chambless, Caputo, Bright & Gallagher, 1984), Anxiety Rating for Children-revised (n = 1; Bernstein, Crosby, Perwien & Borchardt, 1996), Beck Anxiety Inventory (n = 1; Beck, Epstein, Brown & Steer, 1988), Bodily

1 We acknowledge that there have been many top-quality papers published in other journals and, in turn, there have been several low-quality treatment studies published in the journals used for this project. However, these journals were selected as an initial means of increasing the likelihood of obtaining high quality studies that are more homogeneous in design. 2 The relevant statistics were requested from the corresponding author in studies where this information was not reported. These studies were included in the metaanalysis if the authors provided the relevant information.

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Sensation Questionnaire (n = 4; Chambless et al., 1984), CAPS (n = 8; Blake et al., 1995), Child Behavior Checklist (n = 1; Achenbach, 1991), Children's Global Assessment Scale (n = 1; Shaffer, Gould, Brasic et al., 1983), Connors Parent Rating Scale (n = 1; Connors, 1989), Fear Survey Schedule for Children (n = 1; Ollendick, 1983), Fear Questionnaire (n = 2; Marks & Mathews, 1979), Impact of Events Scale (n = 2; Horowitz, Wilner & Alvarez, 1979), Liebowitz Social Anxiety Scale for Children and Adolescents (n = 1; Masia-Warner et al., 2003), Life Areas Questionnaire (n = 1; Keane, Fairbank, Caddell & Zimering, 1989), Panic Disorder Severity Scale (n = 2; Shear et al., 1997), Posttraumatic Stress Diagnostic Scale (n = 1; Foa, 1995), Post-traumatic Stress Scale (n = 1; Reed & Enright, 2006), Penn State Worry Questionnaire (n = 1; Meyer, Miller, Metzer & Borkovec, 1990), PTSD Symptom Scale (n = 1; Foa, Riggs, Dancu & Rothbaum, 1993), Revised Children's Manifest Anxiety Scale (n = 5; Reynolds & Richmond, 1978), Screen for Child Anxiety and Related Emotional Disorders (n = 1; Birmaher, Khetarpal, Brent et al., 1997), Social Phobia and Anxiety Inventory (n = 2; Turner, Beidel, Dancu & Stanley, 1989), Social Phobia Scale (n = 4; Mattick & Clarke, 1998), Spence Children Anxiety Scale (n = 1; Spence, 1998), structured interview for PTSD (n = 1; Davidson, Malik & Travers, 1997), Yale–Brown Obsessive Compulsive Scale (n = 7; Goodman et al., 1989).

2.3. Operationalizing comorbidity

Fig. 1. Flow chart of studies identified and included in the meta-analysis.

The present study coded for overall comorbidity percentage (i.e., percentage of sample having at least 1 comorbid disorder of any type) as well as specific comorbidities for anxiety disorders, major depressive disorder, bipolar disorder, substance use disorders, personality disorders, developmental disorders, and externalizing disorders. Thus, eight different comoribidity percentages were coded for each study. When overall comorbidity was not reported and

Table 1 Study, journal, disorder, treatment group, sample size, and percent comorbidity. Authors

Journal

Population Disorder

Treatment group(s) (N)

Total comorbidity %

Carlbring, Westling, Ljungstrand, Ekselius & Andersson, 2001 Schmidt et al., 2003

BT

Adult

Panic disorder

BT

Adult

Panic disorder

Carlbring et al., 2005

BRAT

Adult

Panic disorder

Benjamin, Levine, Fux, Aviv et al., 1995

AJP

Adult

Panic disorder

Carlbring et al., 2006

AJP

Adult

Panic disorder

Milrod et al., 2007

AJP

Adult

Panic disorder

Clark et al., 1999

JCCP

Adult

Panic disorder

Goldstein, de Beurs, Chambless & Wilson, 2000

JCCP

Adult

Panic disorder

Williams & Zane, 1989

BRAT

Adult

Agoraphobia

Zane & Lloyd, 1993

BT

Adult

Agoraphobia

Koszycki, Benger, Shlik & Bradwejn, 2007

BRAT

Adult

Social phobia

Stangier, Heidenreich, Peitz, Lauterbach & Clark, 2003

BRAT

Adult

Social phobia

Beidel, Turner & Morris, 2000

JCCP

Child

Social phobia

Clark et al., 2003

JCCP

Adult

Social phobia

Internet CBT (20) Wait-list (20) Group CBT (22) Wait-list (24) CBT (24) Internet CBT (25) Inositol (21) Placebo (21) Internet CBT (26) Wait-list (26) Psychodynamic therapy (26) Applied relaxation (23) Full cognitive therapy (14) Brief cognitive therapy (14) Wait-list (14) EMDR (20) Attention control (20) Wait-list (14) Guided mastery (11) Stimulus exposure (10) Wait-list (6) Guided mastery (19) Stimulus exposure (16) Wait-list (10) Group CBT (18) Mindfulness training (22) Group CBT (26) Individual CBT (24) Wait-list (21) Social skills training (30) Attention control (20) Cognitive therapy (20) Fluoxetine plus exposure (17) Placebo plus exposure (20)

– – 41 41 50 48 0 0 – – 42 56 – – – 43 43 43 50 50 50 73 73 73 18.5 19.2 75 75 75 41 41 43 43 43

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Table 1 (continued) Authors

Journal

Population Disorder

Andersson et al., 2006

JCCP

Adult

Clark et al., 2006

JCCP

Adult

Masia-Warner et al., 2005

JACP

Child

Klein, Kiplewicz & Kanner, 1992

JAACAP Child

Keane et al., 1989

BT

Adult

Paunovic & Ost, 2001

BRAT

Adult

Blanchard et al., 2003

BRAT

Adult

Ehlers, Clark, Hackmann, McManus & Fennell, 2005 Frank, Kosten, Gillier & Dan, 1988

BRAT

Adult

AJP

Adult

Neylan et al., 2006

AJP

Adult

Sijbrandij et al., 2007

AJP

Adult

Tarrier et al., 1999

JCCP

Adult

Resick, Nishith, Weaver, Astin & Feuer, 2002

JCCP

Adult

Lange et al., 2003

JCCP

Adult

Neuner, Schauer, Klaschik, Karunakara & Elbert, 2004

JCCP

Adult

Foa et al., 2005

JCCP

Adult

McDonagh et al., 2005

JCCP

Adult

Monson et al., 2006

JCCP

Adult

Reed et al., 2006

JCCP

Adult

King et al., 2000

JAACAP Child

Cohen, Deblinger, Mannarino & Steer, 2004 JAACAP Child Cohen, Mannarino, Perel & Staron, 2007

JAACAP Child

Smith et al., 2007

JAACAP Child

Freedman & Enright, 1996

JCCP

Adult

Gosselin, Ladouceur, Morin, Dugas & Baillargeon, 2006 Woodward, 1980

JCCP

Adult

BRAT

Adult

Chambless, 1990

BT

Adult

McReynolds & Tori, 1972

JCCP

Adult

Silverman et al., 1999

JCCP

Child

Ost, Svensson, Hesstrom & Lindwall, 2001

JCCP

Child

Tolin et al., 2007

BT

Adult

Social phobia

Treatment group(s) (N)

Total comorbidity %

Internet CBT (32) Wait-list (32) Social phobia Exposure + applied relaxation(21) Cognitive therapy (21) Wait-list (20) Social phobia School-based intervention (18) Wait-list (17) Separation Anxiety Disorder Imipramine (11) Placebo (10) PTSD Implosive flooding (11) Wait-list (13) PTSD CBT (7) Exposure (9) PTSD CBT (26) Supportive therapy (26) Wait-list (24) PTSD Cognitive therapy (14) Wait-list (14) PTSD Imipramine (12) Phenelzine(11) Placebo (11) PTSD Guanfacine (29) Placebo (34) PTSD Brief CBT (52) Wait-list (46) PTSD Imaginal exposure (27) Cognitive therapy (29) PTSD Cognitive processing (41) Prolonged exposure (40) Wait-list (32) PTSD Internet CBT (69) Wait-list (32) PTSD Narrative exposure (15) Supportive therapy (13) Psychoeducation (12) PTSD Prolonged exposure (52) Prolonged exposure plus cognitive therapy (44) Wait-list (25) PTSD CBT (17) Problem solving therapy (20) Wait-list (20) PTSD Cognitive processing (30) Wait-list (30) PTSD Forgiveness therapy (10) Attention control (10) PTSD CBT w/child (12) CBT w/child plus parent (12) Wait-list (12) PTSD Trauma focused CBT (88) Child-centered therapy (88) PTSD CBT plus sertraline (11) CBT plus placebo (11) PTSD CBT (12) Wait-list (12) Sexual abuse survivor Forgiveness therapy (6) Wait-list (6) GAD CBT (31) Supportive therapy (27) Neurotic anxiety Cognitive restructuring (7) Systematic desensitization (7) Cognitive restructuring plus systematic desensitization (6) Wait-list (7) Specific phobia agoraphobia Massed exposure (9) Massed exposure (7) Spaced exposure (7) Specific phobia Systematic desensitization (10) Relaxation training (9) Wait-list (9) Specific phobia Self-control treatment (32) Contingency management (33) Education support (16) Specific phobia One session exposure w/parent (20) One session exposure w/o parent (21) Wait-list (20) OCD Therapist administered ERP (21) Self-administered ERP (20)

28 28 55 55 55 50 47.1 43 43 – – – – 41 63 42 50 29 – – – – – 43 45 – – – – – – – – – – 67 67 67 14 9 9 73.3 73.3 – – 58 58 58 – – 64 64 75 83 – – 80 80 – – – – – – – – – – 72 72 72 24 36 40 29 55

(continued on next page)

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Table 1 (continued) Authors

Journal

Population Disorder

Treatment group(s) (N)

Total comorbidity %

Pato, Pigott, Hill & Grover, 1991

AJP

Adult

OCD

Foa et al., 2005

AJP

Adult

OCD

Riddle, Scahill, King & Hardin, 1992

JAACAP Child

OCD

Riddle, Reeve, Yaryura-Tobias, Yang, Claghorn et al., 2001 Barrett, Healy-Farrell & March, 2004

JAACAP Child

OCD

JAACAP Child

OCD

Storch et al., 2007

JAACAP Child

OCD

Al-Kubaisy, Marks, Logsdail, Marks et al., 1992

BT

Adult

Mixed

– – 0 0 0 0 64 64 7 8 79 79 79 70 75 – – –

Kendall, 1994

JCCP

Child

Mixed

Kendall et al., 1997

JCCP

Child

Mixed

Silverman et al., 1999

JCCP

Child

Mixed

Rapee, Abbott & Lyneham, 2006

JCCP

Child

Mixed

Barrowclough et al., 2001

JCCP

Adult

Mixed

Bermstein et al., 2000

JAACAP Child

Mixed

Manassis et al., 2002

JAACAP Child

Mixed

Heyne et al., 2002

JAACAP Child

Mixed

Birmaher et al., 2003

JAACAP Child

Mixed

Buspirone (9) Clomiprimine(9) ERP (21) Clomiprimine (27) ERP + Clomiprimine (31) Placebo (26) Fluoxetine (7) Placebo (6) Fluvoxamine (57) Placebo (63) Individual family CBT (24) Group family CBT (29) Wait-list (24) Weekly CBT (20) Intensive CBT (20) Self-exposure plus Therapist-directed exposure (27) Self-exposure without Therapist-directed exposure (26) Self-relaxation (27) CBT (27) Wait-list (20) CBT (60) Wait-list (34) Group CBT (37) Wait-list (19) Bibliotherapy CBT (61) Group CBT (76) Wait-list (75) CBT (19) Supportive therapy (23) CBT plus Imipramine (31) CBT plus placebo (32) Group CBT (37) Individual CBT (41) Individual CBT w/child (21) CBT w/child plus parent training (20) Parent and teacher training (20) Fluoxetine (37) Placebo (37)

60 60 48 48 – – 82 82 82 23 23 – – 66 66 39 39 39 – –

BT = Behavior Therapy; BRAT = Behaviour Research and Therapy; AJP = American Journal of Psychiatry; JCCP = Journal of Consulting and Clinical Psychology; JACP = Journal of Abnormal Child Psychology; JAACAP = Journal of the American Academy of Child and Adolescent Psychiatry; PTSD = Post-Traumatic Stress Disorder; GAD = Generalized Anxiety Disorder; OCD = Obsessive–Compulsive Disorder; CBT = Cognitive–Behavioral Therapy; ERP = Exposure and Response Prevention; – not available.

comorbidity was only reported separately for individual diagnoses (e.g., 20% panic disorder, 44% GAD, 8% OCD), we used the percentage from the most frequently occurring comorbid disorder (e.g., 44% GAD in this example). This was the most conservative means of coding. Adding the comorbidity percentages together would be an overestimate because it is possible that individuals have more than 1 comorbid disorder. For example, an individual could have panic disorder, GAD, and OCD, in which case 1 individual would be contributing to the comorbidity percentages of three different disorders. Using the comorbidity percentage from the most commonly occurring single disorder provides the best estimate because the sample necessarily contained as much comorbidity as indicated by the one disorder, but did not necessarily contain more, as all participants with GAD could have also had the other disorders. When studies did not report comorbidity rates, the authors were contacted to obtain the relevant information for inclusion in the meta-analysis. RCTs most commonly report completer analyses, as opposed to intent-to-treat analyses (Westen, Novotny & Thompson-Brenner, 2004). When a study reported both completer and intent-to-treat analyses, we always used the completer analyses in order to make results from each study more comparable. Some studies reported multiple follow-up periods. We always coded the first follow-up time point. This was done to control for measurement reactivity, such that each data point we coded for the follow-up variable was the third measurement point in each study reporting follow-up data. Where current comorbidity was

reported separate from past comorbidity, we always used current comorbidity because this was the most frequently reported statistic. Treatment length for studies providing a range was computed as the midpoint (e.g., 16-20 sessions was regarded as 18 sessions). 2.4. Sample description One hundred forty-eight treatment samples were identified for post-treatment effects, with a combined N of 3534. Seventy-seven follow-up samples were identified, with a combined N of 1807. Of the 148 post-treatment samples, 27 were comprised of patients with mixed or “neurotic” anxiety,3 17 social phobia, 17 OCD, 26 panic disorder and/or agoraphobia, 47 PTSD or sexual assault survivors, 10 specific phobias, 2 GAD, and 2 SAD. Eighty samples received CBT, 3 dynamic therapy, 11 drug treatment, 18 placebo or attention control, 31 wait-list, 4 CBT + drug treatment, and 1 mindfulness meditation. One hundred samples were of adult patients, and 48 of child or adolescent patients. Mean (SD) participant age was 32.23 (18.00) years. Mean (SD) percentage of female participants was 59.80% (23.52). 3 Neurotic may be considered an older construct of GAD, although it could be argued that it is distinct from a mixed anxiety group (i.e., group comprised of individuals with multiple diagnoses). However, one sample was ‘neurotic,’ so for the purposes of clarity and parsimony they were combined with the mixed group.

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Mean (SD) rates of overall comorbidity for each diagnostic group (post-treatment only) were as follows: mixed or “neurotic” anxiety 54.07% (20.34), social phobia 46.58% (17.64), OCD 40.60% (34.53), panic disorder or agoraphobia 45.65% (20.43), PTSD or sexual assault survivors 52.39% (21.39), specific phobia 52.67% (21.82), GAD 80.00% (0.00),and SAD 43.00% (0.00). Due to the lack of variability in the GAD and SAD samples, all but these samples were included in a one-way ANOVA, which revealed no significant difference in mean overall comorbidity rates across diagnostic categories, F5,85 = 0.747, p = 0.591. Due to the small number of studies in each cell, it was not possible to analyze all 7 treatment classifications by all 8 diagnostic groups. Therefore, the 7 treatment classifications were condensed into theoretically active treatments (CBT, dynamic therapy, drug treatment, CBT + drug treatment, mindfulness) vs. theoretically inactive treatments (placebo/attention control, wait-list). Proportions of samples (post-treatment only) receiving active treatment were as follows: mixed or “neurotic” anxiety 74.1%, social phobia 70.6%, OCD 76.5%, panic disorder or agoraphobia 65.4%, PTSD or sexual assault survivors 59.6%, specific phobia 70.0%, GAD 50.0%, and SAD 50.0%. Rates of active vs. inactive treatment did not differ significantly by diagnostic group, χ2 (7) = 3.160, p = 0.870. 2.5. Analysis of treatment effects 2.5.1. Intervention specificity Table 2 depicts effect size estimates (d) at post-treatment and follow-up for CBT, dynamic therapy, drug treatment, placebo/ attention control, wait-list, CBT + drug treatment, and mindfulness interventions for the total sample. As can be seen in the Table, all treatments were associated with significant improvement at posttreatment; all but the placebo/attention control were associated with significant improvement at follow-up. Significant between-group heterogeneity was found at post-treatment (Qbetween = 168.12, p b 0.001) and at follow-up (Qbetween = 39.96, p b 0.001). At both time points, active treatments were associated with greater effects than were inactive treatments (placebo/attention control or waitlist). As shown in Tables 3 and 4, this pattern of findings was generally consistent for adult and youth samples. 2.5.2. Disorder specificity Table 5 shows effect size estimates at post-treatment and followup for mixed or “neurotic” anxiety, social phobia, OCD, panic disorder and/or agoraphobia, PTSD or sexual assault survivors, specific phobia, GAD, and SAD for the total sample. With the exception of SAD, all diagnostic categories were associated with significant improvement at post-treatment and follow-up. There was a nonsignificant trend with respect to between-group heterogeneity at post-treatment (Qbetween = 13.88, p = 0.053), but not at follow-up (Qbetween = 7.99, p = 0.239). As shown in Tables 6 and 7, this pattern of findings was also general consistent for adult and youth samples. 2.6. Analysis of comorbidity effects Of the 148 available post-treatment comparisons, 105 reported comorbidity rates and 43 did not. Effect sizes did not differ between comparisons reporting (d = 0.99, 95% CI = 0.86–1.12) and not reporting (d = 1.01, 95% CI = 0.74–1.28) comorbidity rates (Qbetween =0.02, p = 0.893).4

4 Although the overall percentage of comorbidity for comparisons involving child studies (n = 40, M = 56.93, SD = 19.47) was significantly higher than those of adult studies (n = 55, M = 43.11, SD = 23.79), t (93) = 3.01, p = 0.003, limited power prevented separating the two samples for the analysis of comorbid effects.

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2.6.1. Intervention specificity Of the 105 comparisons reporting comorbidity rates, 95 provided an overall rate of diagnostic comorbidity. As shown in Fig. 2, percentage of overall comorbidity was unrelated to effect size at post-treatment or at follow-up for the total sample. Follow-up analyses indicated that this was the case for CBT (k = 53, z = −0.303, p = 0.762), drug treatment (k = 5, z = 1.202, p = 0.229), placebo/attention control (k = 11, z = 0.821, p = 0.412), wait-list (k = 21, z = −0.612, p = 0.541), and CBT + drug treatment (k = 3, z = −1.347, p = 0.178). Regressions could not be calculated for dynamic therapy or mindfulness, as these conditions only had 1 study each in which percent comorbidity was reported. As shown in Figs. 3 and 4, the absence of a relation between overall comorbidity and effect size at post-treatment or at follow-up was observed for adult and youth samples. 2.6.2. Disorder specificity Examination of studies according to diagnostic sample revealed a significant negative relationship between percentage of overall comorbidity and effect size for mixed or “neurotic” anxiety samples (k = 14, z = − 2.622, p = 0.009), with higher comorbidity rates associated with lower post-treatment effect size. Conversely, there was a significant positive relationship between percentage of overall comorbidity and effect size for samples of panic disorder and/or agoraphobia (k = 13, z = 3.814, p b 0.001) and for PTSD or sexual abuse survivors (k = 22, z = 3.153, p = 0.002); the relationship evidenced a nonsignificant trend for samples of OCD (k = 15, z = 1.959, p = 0.05). In each of these groups, higher rates of overall comorbidity were associated with greater post-treatment effect sizes. There was no significant relationship between percentage of overall comorbidity and effect size for samples of social phobia (k = 17, z = 0.980, p = 0.327) or specific phobia (k = 6, z = 0.566, p = 0.571). The relationship could not be calculated for studies of GAD or SAD due to the low number of samples (2 each) providing overall comorbidity rates. At follow-up, the significant positive relationship between percentage overall comorbidity and effect size remained significant for samples of panic disorder and/or agoraphobia (k = 8, z = 3.896, p b 0.001), with higher rates of overall comorbidity associated with greater post-treatment effect sizes. No significant relationship was detected between percentage overall comorbidity and follow-up effect size for mixed or “neurotic” anxiety (k = 9, z = 0.260, p = 0.795), OCD (k = 4, z = 1.688, p = 0.091), PTSD or sexual abuse survivors (k = 13, z = −1.232, p = 0.218), social phobia (k = 10, z = −1.153, p = 0.249), or specific phobia (k = 5, z = 0.882, p = 0.378). Examination of the relationship between bipolar disorder comorbidity and effect size was not possible due to the lack of variability in rates of this condition. No relationship was found between effect size and rates of substance use disorders (z = − 0.322, p = 0.748), externalizing disorders (z = −0.302, p = 0.763), personality disorders (z = 0.031, p = 0.975), depressive disorders (z = −0.305, p = 0.760), or anxiety disorders (z = −1.570, p = 0.116). A significant positive relationship was found between effect size and rates of developmental disorder comorbidity (z = 2.026, p = 0.043), with higher rates of developmental disorders associated with stronger effect size at posttreatment. 3. 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 expressed the concern that exclusion criteria for these disorders “often eliminated

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Table 2 Within-group effect sizes at post-treatment and follow-up by treatment category for the total sample. Post-treatment

Follow-up

95% CI

95% CI

Treatment

k

d

Lower

Upper

p

k

d

CBT Dynamic therapy Drug treatment Placebo/attention control Wait-list CBT + drug Mindfulness Overall

80 3 11 18 31 4 1 148

1.37 2.10 1.00 0.49 0.24 1.50 0.65 0.63

1.21 1.56 0.64 0.34 0.12 0.49 0.04 0.55

1.53 2.63 1.36 0.63 0.35 2.51 1.25 0.70

b0.001 b0.001 b0.001 b0.001 b0.001 0.004 0.037 b0.001

60 2 – 7 7 1 – 77

1.50 2.67 – 0.32 0.63 1.38 – 1.30

Lower 1.32 1.72 – − 0.10 0.11 0.63 – 1.14

Upper

p

1.68 3.62 – 0.74 1.16 2.13 – 1.45

b0.001 b0.001 – 0.131 0.018 b0.001 – b0.001

CBT = cognitive–behavioral therapy. k = number of trials. d = effect size. CI = confidence interval.

more troubled and difficult-to-treat patients” (Westen & Morrison, 2001, p. 880). However, a review of the literature suggests that comorbidity is common in RCTs (Stirman, DeRubeis, Crits-Christoph & Brody, 2003). Furthermore, the present investigation suggests degree of comorbidity in RCTs of anxiety disorders is substantial and pervasive. To the extent that frequent comorbidity with other disorders is representative of real-life patients with anxiety disorders, these findings suggest that treatments deemed efficacious based on RCTs are suitable for real world patients. The present meta-analytic investigation, then, examined the influence of diagnostic comorbidity on both active and inactive treatment outcome in the anxiety disorders. The findings revealed that comorbidity was generally unrelated to anxiety disorder treatment effect sizes at post-treatment and follow-up. This pattern of findings was consistent for both active and inactive interventions suggesting that the presence of comorbidity does not influence treatment outcome for the anxiety disorders and this appears to be the case for treatments with specific and nonspecific mechanisms of action. According to Klerman (1990), there are at least three ways one can conceptualize the co-occurrence of multiple disorders: (a) chronological, in which if multiple diagnoses are

observed, the primary diagnosis developed first; (b) causal, in which secondary diagnosis are caused by another co-existing disorder; and (c) symptomatic predominance, in which the primary diagnosis is associated with the greatest distress and dysfunction. Accordingly, treatment outcome of anxiety disorders that are more causal of, or have symptom predominance over, co-occurring disorders may not necessarily be influenced by comorbidity; thus, the lack of a correlation between comorbidity and effect size might be expected under this condition. Although commendable efforts have been made to develop strategies to address the potential negative impact of various comorbid conditions during treatment of anxiety disorders (e.g., Abramowitz, 2004), these findings suggests that such efforts may be premature and in some cases unnecessary. In fact, studies have shown that rather than modifying treatments to address the influences of comorbid conditions, focusing specifically on core symptoms in some anxiety disorders may maximize outcome for the anxiety disorder as well as comorbid conditions (Craske et al., 2007; Tsao et al., 2002; see Barlow, Allen & Choate, 2004). The possibility remains, however, that the relationship between comorbidity and treatment outcome may vary as a function of diagnosis. Indeed, a significant positive

Table 3 Within-group effect sizes at post-treatment and follow-up by treatment category for the adult sample. Post-treatment

Follow-up

95% CI

95% CI

Treatment

k

d

Lower

Upper

p

k

d

CBT Dynamic therapy Drug treatment Placebo/attention control Wait-list CBT + drug Mindfulness Overall

54 3 7 11 22 2 1 100

1.49 2.10 0.84 0.46 0.24 1.49 0.65 0.64

1.28 1.56 0.40 0.27 0.12 0.02 0.04 0.55

1.69 2.63 1.29 0.66 0.35 2.97 1.25 0.74

b0.001 b0.001 b0.001 b0.001 b0.001 0.048 0.037 b0.001

44 2 – 6 6 1 – 59

1.54 2.67 – 0.28 0.63 1.38 – 1.30

Lower

– − 0.21 0.04 0.63 – 1.12

Lower

1.31 1.72

Upper

p

1.76 3.62 – 0.76 1.23 2.13 – 1.49

b 0.001 b 0.001 – 0.262 0.037 b 0.001 – b 0.001

Upper

p

1.62 – – 1.24 1.53 – – 1.44

b 0.001 – – 0.135 0.095 – – b 0.001

Table 4 Within-group effect sizes at post-treatment and follow-up by treatment category for the youth sample. Post-treatment

Follow-up

95% CI

95% CI

Treatment

k

d

CBT Dynamic therapy Drug treatment Placebo/attention control Wait-list CBT + drug Mindfulness Overall

26 – 4 7 9 2 – 48

1.12 – 1.27 0.51 0.28 1.58 – 0.64

Lower 0.89 – 0.67 0.27 0.08 − 0.56 – 0.52

Upper

P

k

d

1.35 – 1.87 0.74 0.49 3.72 – 0.77

b 0.001 – b 0.001 b 0.001 0.006 0.148 – b 0.001

16 – – 1 1 – – 18

1.36 – – 0.54 0.70 – – 1.20

1.09 – – -0.17 − 0.12 – – 0.96

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Table 5 Within-group effect sizes at post-treatment and follow-up by diagnostic category for the total sample. Post-treatment

Follow-up

95% CI

95% CI

Diagnosis

k

d

Lower

Upper

p

k

d

Lower

Upper

p

Mixed or “neurotic” Social phobia OCD Panic and/or agoraphobia PTSD or sexual assault Specific Phobia GAD SAD Overall

27 17 17 26 47 10 2 2 148

0.81 0.77 1.36 1.04 1.12 0.71 1.17 0.35 0.63

0.61 0.48 0.96 0.72 0.87 0.27 0.35 − 0.33 0.55

1.01 1.06 1.76 1.36 1.38 1.14 1.99 1.03 0.70

b0.001 b0.001 b0.001 b0.001 b0.001 0.001 0.005 0.310 b0.001

15 10 4 13 27 6 2 – 77

1.20 1.02 1.61 1.47 1.56 0.97 1.07 – 1.30

0.94 0.59 0.83 1.06 1.17 0.60 0.17 – 1.14

1.46 1.45 2.38 1.88 1.95 1.34 1.97 – 1.45

b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 0.020 – b0.001

OCD = Obsessive–Compulsive Disorder. PTSD = post-traumatic stress disorder. GAD = Generalized Anxiety Disorder. SAD = Separation Anxiety Disorder. k = number of trials. d = effect size. CI = confidence interval.

association was observed between comorbidity and effect size for panic disorder and/or agoraphobia, PTSD/sexual abuse survivors, and OCD to a degree. However, no relationship was found between comorbidity and effect size for social and specific phobia. The positive association between comorbidity and treatment effect size for panic disorder and/or agoraphobia, PTSD/sexual abuse survivors, and OCD is consistent with prior research. For example, research has shown that presence of psychiatric comorbidity is associated with more favorable outcome for some anxiety disorder patients (Chambless, Renneberg, Goldstein & Gracely, 1992; Wetherell et al., 2005). Such findings could mean that anxiety disorder patients with psychiatric comorbidity change more than other patients, which could reflect regression to the mean. These findings may also suggest

that anxiety disorder patients with psychiatric comorbidity show bigger differential treatment effects, which could mean that they respond better to active treatments or that they are less likely to respond to control conditions. However, these interpretations do not explain why a significant positive relationship between overall comorbidity and treatment outcome would be observed only for panic disorder, PTSD, and OCD. No significant difference in comorbidity rates across the anxiety disorder diagnostic categories was found suggesting that there may be some unique features of panic disorder, PTSD, and OCD (relative to other anxiety disorders) that accounts for the positive association between comorbidity and treatment effect. Delineating the functional relationship between specific anxiety disorder diagnosis and comorbid conditions may help determine why

Table 6 Within-group effect sizes at post-treatment and follow-up by diagnostic category for the adult sample. Post-treatment

Follow-up

95% CI Diagnosis Mixed or “neurotic” Social phobia OCD Panic and/or agoraphobia PTSD or sexual assault Specific phobia GAD SAD Overall

k 9 13 8 26 38 4 2 – 100

95% CI d

Lower

Upper

p

k

d

Lower

Upper

p

1.00 0.80 1.33 1.04 1.06 1.38 1.17 – 0.64

0.52 0.45 0.86 0.72 0.77 − 0.30 0.35 – 0.55

1.48 1.16 1.79 1.36 1.36 3.06 1.99 – 0.74

b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 0.107 0.005 – b 0.001

8 10 2 13 23 1 2 – 59

1.15 1.02 1.03 1.47 1.48 2.57 1.07 – 1.30

0.55 0.59 0.22 1.06 1.07 1.32 0.17 – 1.12

1.75 1.45 1.84 1.88 1.89 3.82 1.97 – 1.49

b0.001 b0.001 0.013 b0.001 b0.001 b0.001 0.020 – b0.001

OCD = Obsessive–Compulsive Disorder. PTSD = Post-Traumatic Stress Disorder. GAD = Generalized Anxiety Disorder. SAD = Separation Anxiety Disorder. k = number of trials. d = effect size. CI = confidence interval.

Table 7 Within-group effect sizes at post-treatment and follow-up by diagnostic category for the youth sample. Post-treatment

Follow-up

95% CI

95% CI

Diagnosis

k

d

Mixed or “neurotic” Social phobia OCD Panic and/or agoraphobia PTSD or sexual assault Specific phobia GAD SAD Overall

18 4 9 – 9 6 – 2 48

0.73 0.68 1.40 – 1.36 0.57 – 0.35 0.74

Lower 0.52 0.13 0.76 – 0.86 0.33 – − 0.33 0.60

Upper

p

0.94 1.23 2.03 – 1.87 0.80 – 1.03 0.87

b 0.001 0.015 b 0.001 – b 0.001 0.107 – 0.310 b 0.001

k 7 – 2 – 4 5 – – 18

d

Lower

Upper

p

1.21 – 2.22 – 2.26 0.88 – – 1.19

1.03 – 1.67 – 0.72 0.61 – – 1.04

1.39 – 2.78 – 3.81 1.14 – – 1.33

b0.001 – b0.001 – 0.004 b0.001 – – b0.001

OCD = Obsessive–Compulsive Disorder. PTSD = Post-Traumatic Stress Disorder. GAD = Generalized Anxiety Disorder. SAD = Separation Anxiety Disorder. k = number of trials. d = effect size. CI = confidence interval.

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Fig. 2. Regression of percentage comorbidity on effect size at post-treatment (top) and follow-up (bottom) for all studies.

Fig. 3. Regression of percentage comorbidity on effect size at post-treatment (top) and follow-up (bottom) for studies with adult samples.

differences between anxiety disorders in the association between comorbidity and treatment outcome may be observed. For example, when comorbidity is observed, social and specific phobias are often viewed as independent syndromes that coexist with other disorders (i.e., Barlow et al., 1986). Conversely, panic disorder and PTSD (perhaps even OCD) may be syndromes that are causal of, or have symptom predominance over, co-occurring disorders. Distinct symptoms may also inform why differences between anxiety disorders in the association between comorbidity and treatment outcome may be observed. For example, recent research has shown that unlike other anxiety disorders, panic disorder and PTSD are characterized by persistent autonomic arousal (Brown & Mcniff, 2009). Repeated acute episodes of autonomic arousal (i.e., panic attacks, re-experiencing symptoms) in panic disorder and PTSD may be a cause of co-occurring conditions, such as depression or substance use (i.e., Jacobsen, Southwick & Kosten, 2001) and such a functional relationship with comorbid disorders may not be readily observed among other anxiety disorders. Given that comorbid conditions may not necessarily be independent of panic disorder and PTSD, presence of more co-occurring conditions may be an artifact of the severity/dysfunction associated with the anxiety disorders. These differences highlight the need for future research to examine distinct symptom clusters of anxiety disorders and their functional relationship with comorbid conditions as this will have implications for understanding how differences in treatment outcome emerge. Higher comorbidity rates were associated with lower post-treatment effect sizes only for mixed or “neurotic” anxiety samples in the present

investigation, although the effect was not maintained at follow-up. It is well documented that diagnosis and classification of anxiety disorders has important implications for treatment (Brown & Barlow, 1992). This finding suggests that a negative relationship between comorbidity and treatment outcome may be observed when the anxiety disorder diagnosis is not well specified. It should be noted that there is evidence of substantial overlap between anxiety disorders that stem from shared genetic/psychological predispositions (e.g., Barlow, 2002). In fact, dimensional traits (i.e., neuroticism, behavioral inhibition) that account for the covariance between anxiety disorders have been identified (Brown, 2007). However, many of the currently available treatments have been developed specifically for each anxiety disorder rather than the shared underlying vulnerabilities (Barlow et al., 2004; Moses & Barlow, 2006). Attempts to use treatments that have been developed for specific anxiety disorders for those with any anxiety symptoms may yield several complications for which comorbidity is just one. In the absence of a specific diagnosis, the goals of treatments that have been primarily designed for specific problems may become a moving target that is made even more elusive by comorbidity. That is, more comorbidity among those with mixed or “neurotic” anxiety may lead to even less focused treatment resulting in less favorable outcomes. The present investigation also examined if the pattern of findings as to the association between overall comorbidity and treatment outcome in the anxiety disorders can be illuminated by consideration of specific comorbid diagnoses. Prior research has shown that while no differences are observed between success and failure among anxious children with

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Fig. 4. Regression of percentage comorbidity on effect size at post-treatment (top) and follow-up (bottom) for study with youth samples.

regard to presence/absence of comorbidity overall or presence of comorbidity with externalizing disorders specifically, those who had comorbid depression diagnoses were significantly more likely to be in the treatment failure group (Berman, Weems, Silverman & Kurtines, 2000). Furthermore, it has been suggested that some personality disorders may have an adverse impact upon treatment outcome in anxiety disorders (Dreessen & Arntz, 1998). Present findings revealed no association between effect size and rates of substance use disorders, externalizing disorders, personality disorders, depressive disorders, or other anxiety disorders. However, a higher rate of developmental disorders was associated with stronger effect size at post-treatment. It is important to note that a positive association between the presence of specific comorbid disorders and better treatment outcome in the anxiety disorders is not an uncommon finding. For example, prior research has shown that the presence of social phobia at pre-treatment is a significant predictor of favorable response to treatment of panic disorder (Allen et al., 2003; Brown, Antony & Barlow, 1995). One might speculate that social phobia may motivate treatment compliance due to fear of negative evaluation. It is difficult to speculate why a higher rate of developmental disorders would be associated with stronger effect sizes at post-treatment. However, research has shown that higher levels of anxiety among children with pervasive developmental disorders is associated with higher IQ, the presence of functional language use, and with higher levels of stereotyped behaviors (Sukhodolsky et al., 2008). A higher rate of

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developmental disorders may result in a higher rate of children who are better able to benefit from some treatments and/or who are more likely to present with anxiety symptoms that are more amenable to intervention. This investigation offers initial quantitative evidence highlighting complexities in the influence of diagnostic comorbidity on treatment outcome in the anxiety disorders. One conclusion is that the presence of more comorbidity may not always translate into worse outcomes. However, limitations of the present investigation should be considered when interpreting these findings. For example, there is clearly an over-representation of CBT RCTs in the analysis. Although the majority of RCTs that have been evaluated for anxiety disorder treatment have focused mainly on the efficacy of CBT, conducting searches in select journals may have contributed to the likelihood of not indentifying RCTs for other treatment modalities. However, the over-representation of CBT also indicates that more RCTs examining the efficacy of non-CBT anxiety disorder treatments are needed. While the present investigation suggests that various anxiety disorder treatment approaches are not differentially influenced by degree of diagnostic comorbidity, the availability of additional RCTs of treatments other than CBT will be needed to support this claim. Another limitation is that many of the studies included in this meta-analysis excluded certain comorbidities (e.g., schizophrenia), usually the most problematic comorbidities. Therefore, it is difficult to conclude at this point that all comorbidity is unrelated to treatment outcome. To the extent that more serious comorbid disorders are systematically excluded from RCTs, a parsimonious interpretation of these findings is that more of less serious comorbid conditions (i.e., those that are not RCT exclusion criteria) are not associated with treatment outcome. Another inherent limitation in analyzing comorbidity across different RCTs is that inclusion/exclusion criteria will vary across RCTs. For example, some studies may exclude based on substance use, whereas as other may exclude based on depression being the primary clinical feature. Although effect sizes did not differ between comparisons reporting and not reporting comorbidity rates, it is important to note that a sizable minority (29%) of the available post-treatment comparisons did not provide comorbidity rates. Given growing concerns regarding the conceptualization (Lilienfeld, Waldman & Israel, 1994) and interpretation of comorbidity (Krueger & Markon, 2006) in psychopathology, it is surprising that so many anxiety disorder RCTs do not provide such information. It is even more surprising given that comorbidity has important implications for making inferences (i.e., generalizability) about treatment outcome (Brown & Barlow, 1992). Despite such limitations, the present investigation suggests that comorbidity does not necessarily influence anxiety disorder treatment outcome. Furthermore, in specific anxiety disorders where a relationship between treatment outcome and comorbidity is observed, the relationship is not always in the anticipated direction (more comorbidity = worse outcome). These findings also highlight a clear need for additional research examining the nature of the influence of comorbidity on treatment outcome of anxiety disorders. The common observation that comorbidity is associated with poorer outcomes can reflect either a prognostic or prescriptive view. A prognostic variable is one that predicts outcome irrespective of the treatment, whereas a prescriptive variable predicts a different pattern of outcomes between two, or more, treatment modalities (Hollon & Beck, 1986). From a prognostic view, these findings suggest that overall comorbidity is significantly positively associated with treatment outcome for panic disorder, PTSD, and perhaps OCD when holding type of treatment constant. However, the prescriptive implications of these finders are less clear. Identification of markers that could be used prescriptively to determine if different kinds of anxiety disorder patients with varying levels of comorbidity respond differentially to different kinds of treatments would have great clinical utility. Treatment outcome

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research along these lines may ultimately lead to the development of more efficient interventions that maximize treatment outcome in the anxiety disorders.

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

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