Copyright 1992 by the American Psychological Association, Inc. 0022-006X/92/S3.00

Journal of Consulting and Clinical Psychology 1992, Vol. 60, No. 6, 835-844

Comorbidity Among Anxiety Disorders: Implications for Treatment and DSM-IV Timothy A. Brown and David H. Barlow

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Center for Stress & Anxiety Disorders University at Albany, State University of New \brk Research on comorbidity among psychological disorders is relatively new. Yet, comorbidity data have fundamental significance for classification and treatment. This significance is particularly apparent in the anxiety disorders, which, prior to DSM-III-R, were subsumed under disorders considered more significant (e.g., psychotic and depressive disorders). After considering definitional, methodological, and theoretical issues of comorbidity, data on comorbidity among the anxiety disorders are reviewed as well as data on comorbidity of anxiety disorders with the depressive, personality, and substance use disorders. Treatment implications are presented with preliminary data on the effects of psychosocial treatment of panic disorder on comorbid generalized anxiety disorder. Implications of comorbidity for research on the nature of psychopathology and the ultimate integration of dimensional and categorical features in our nosology are considered.

is a prominent feature of a host of disorders, GAD was frequently excluded as an additional diagnosis. Nevertheless, studies using the DSM-III-R classification system indicate that the majority of patients presenting with an anxiety disorder evidence at least one additional disorder (e.g., de Ruiter, Rijken, Garssen, van Schaik, & Kraaimaat, 1989; Moras, Di Nardo, Brown, & Barlow, 1991; Sanderson, Di Nardo, Rapee, & Barlow, 1990). In a large-scale (N= 468) study recently completed at the Center for Stress & Anxiety Disorders (Moras et al., 1991), 50% of patients with a principal anxiety disorder had at least one additional clinically significant anxiety or depressive disorder at the time of their assessment. Prior studies have obtained comorbidity rates that match or exceed this figure (e.g., de Ruiter et al., 1989; Sanderson, Di Nardo, Rapee, & Barlow, 1990). These high rates of comorbidity may have substantial implications in terms of our understanding of the etiology, nature, and treatment of the anxiety disorders. In this article, we review the extant literature pertaining to the empirical and theoretical aspects of comorbidity with particular emphasis on the implications of these issues for the treatment of anxiety disorders.

Among the psychological disorders, anxiety disorders are the most common. Indeed, data from the Epidemiologic Catchment Area study suggest that approximately 15% of the population suffer from a Diagnostic and Statistical Manual of Mental Disorders (3rd ed.; DSM-III; American Psychiatric Association, 1980) anxiety disorder at some point during their lifetimes (Regier, Burke, & Burke, 1990). Moreover, anxiety is one of the most prevalent problems prompting the need for medical and mental health services (Boyd, 1986; Marsland, Wood, & Mayo, 1976). Over the past decade, research on the nature and treatment of anxiety and its disorders has burgeoned (cf. Barlow, 1988). Nevertheless, as is the case with all psychological disorders, it has been only recently that researchers have examined comorbidity among the anxiety disorders. One of the principal reasons for the lack of research on the rates and impact of comorbidity was the existence of hierarchical exclusionary rules present in diagnostic classification systems prior to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R; American Psychiatric Association, 1987). Under these systems (e.g., DSM-III), many diagnoses were excluded if their defining symptoms occurred only during the course of a coexisting disorder that occupied a higher position in the hierarchy. Most broad categories of disorders ranked above anxiety disorders. For instance, major depression (MD) occupied a higher position than the anxiety disorders in DSMIII, and thus the presence of MD often precluded assigning an anxiety disorder diagnosis. Whereas all of the anxiety disorders were affected by this system, the diagnosis of generalized anxiety disorder (GAD), a residual category in DSM-III, was perhaps the most affected. Because persistent generalized anxiety

Comorbidity: Definitional, Methodological, and Theoretical Considerations In the majority of studies, comorbidity refers to the co-occurrence of at least two different disorders in the same individual. Although the majority of comorbidity research has been at the diagnostic (or syndrome) level (i.e., the presence of co-occurring DSM-III disorders), another approach is to study the extent to which certain symptoms or symptom patterns tend to co-occur (Blashfield, 1990; Di Nardo & Barlow, 1990; Moras & Barlow, 1992). For example, many patients with panic disorders (PDs) also present with hypochondriacal features of a severity level insufficient to warrant a diagnosis of hypochondriasis. The presence of these features may have substantial etiological

Correspondence concerning this article should be addressed to Timothy A. Brown, Center for Stress & Anxiety Disorders, University at Albany, State University of New York, 1535 Western Avenue, Albany, New York 12203.

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TIMOTHY A. BROWN AND DAVID H. BARLOW

and treatment implications; therefore, examination of comorbidity at purely the diagnostic level may result in a significant loss of important information. Whereas DSM-IH-R is principally a categorical system that assumes discontinuity and qualitative differences among disorders, examination of co-occurrence at the symptom level espouses a more dimensional or quantitative approach (Moras & Barlow, 1992). Indeed, researchers have recently proposed alternative classification systems that simply measure the presence of various symptoms on a continuum and use these data in a dimensional analysis (Blashfield, 1990; Di Nardo & Barlow, 1990; Frances, Widiger, &Fyer, 1990). Comorbidity can be examined either cross-sectionally or longitudinally. In the cross-sectional analysis, one records the cooccurrence of disorders for which a person meets criteria at one point in time, whereas the longitudinal method entails analyzing all diagnoses for which a person met criteria over a specified time frame (e.g., lifetime). Also relevant is the distinction between primary and secondary diagnoses. As Klerman (1990) noted, there are at least three uses of the primary-secondary distinction: (a) chronological, in which, if multiple diagnoses are present, the primary diagnosis is the one that came first temporally; (b) causal, in which secondary diagnoses are regarded as being caused by other another existing disorder (cf. organic anxiety disorder; primary vs. secondary dysthymia); and (c) symptomatic predominance, in which the primary diagnosis is the one judged to be associated with the greatest distress or life interference. In our research efforts, we adopted an approach consistent with the third definition, but we used the terms principal and additional, in part to mitigate confusion associated with prior terminology. Implications for Diagnostic Reliability and Classification Research on the rates and impact of comorbidity is directly influenced by the degree to which the disorders in question are made up of distinct features, overlapping features, or both. For example, with regard to classification, extremely high rates of comorbidity may be indicative of poor discriminant validity among the diagnostic categories; that is, the diagnostic system may be artifactually distinguishing phenomena that would be more parsimonious if combined (Blashfield, 1990). In addition, the extent of symptom overlap and distinctiveness may be reflected also by the reliability of the diagnostic categories. Although there are numerous factors that potentially contribute to the reliability of the DSM-IH-R anxiety disorders (e.g., ambiguity in diagnostic criteria, consistency of patient report, and fluctuations in symptom course), the distinctiveness of the criteria that compose the syndromes is one such factor. To illustrate this point, Table 1 shows kappas for principal anxiety disorders derived from a large-scale study (N - 267) that was recently conducted at the Center for Stress & Anxiety Disorders (Di Nardo, Moras, Barlow, Rapee, & Brown, in press). Kappas were calculated on the basis of diagnoses assigned during two independent administrations of the Anxiety Disorders Interview Schedule—Revised (ADIS-R; Di Nardo & Barlow, 1988). As can be seen in Table 1, excellent reliability was obtained for principal diagnoses of simple phobia, social phobia, and obsessive-compulsive disorder (OCD); good reli-

Table 1 Interrater Reliability of Current DSM-III-R Anxiety Disorder Diagnoses (n = 267) Principal or additional15

Principal" Diagnosis

PD PDA (mild) PDA (moderate) PDA (severe)

GAD Simple phobia Social phobia

OCD PTSD PDA (all levels)

kappa

;

kappa

38 89 50

.43 .60 .71

7

.44 .57

44 98 52 8 108

.39 .61 .70 .40 .53 .63 .66

38 21 45 19 3 131

.82 .79 .80 .46 .72

47

84 24 8 142

.75 .55 .71

Note. DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev); ADIS-R = Anxiety Disorders Interview ScheduleRevised; PD = panic disorder; PDA = panic disorder with agoraphobia (severity of agoraphobia); GAD = generalized anxiety disorder; OCD = obsessive-compulsive disorder; PTSD = posttraumatic stress disorder; n = number of cases in which the diagnosis was assigned by either or both raters. " Principal diagnosis refers to the one judged to be associated with the greatest distress or impairment. b All cases that were assigned the diagnosis at a severity of 4 or above on the ADIS-R 0-8 point clinical severity rating scale.

ability was obtained for panic disorder with mild and moderate agoraphobia (PDA mild and PDA moderate, respectively); fair reliability was obtained for GAD, PD, PDA (severe), and posttraumatic stress disorder (PTSD). Further inspection of these data reveals that kappas for social phobia and simple phobia dropped from "excellent" when only principal diagnoses were considered to "good" when diagnoses anywhere in the clinical picture were considered (i.e., consideration of both principal and additional diagnoses). It is interesting to note the findings of several studies indicating that simple and social phobia are the most frequently assigned additional diagnoses when another anxiety disorder diagnosis is assigned as principal (e.g., de Ruiter et al., 1989; Di Nardo & Barlow, 1990; Sanderson, Di Nardo, Rapee, & Barlow, 1990). Di Nardo et al. (in press) asserted that one reason the reliability of simple and social phobia declined when examined as additional diagnoses was that, in addition to disagreements involving threshold (i.e., clinical vs. subclinical phobias), in many instances diagnosticians disagreed on whether the avoidance associated with the specific object or social context was an associated feature of another disorder (i.e., PDA) as opposed to an independent disorder. Thus, situational avoidance as an overlapping feature may have contributed to the lower reliability. Similarly, the principal diagnoses of PD and GAD were among the disorders with the lowest diagnostic agreement (Di Nardo et al., in press; cf. Mannuzza et al., 1989).' As elaborated on later, this in part may be 1 In Di Nardo et al. (in press), kappas were low for the diagnoses of PTSD and PDA (severe) as well. However, given the infrequency with which these diagnoses were assigned in this study, little can be con-

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SPECIAL SECTION: ANXIETY DISORDERS

because the core features of PD and GAD represent characteristics present to some extent in all of the anxiety disorders. Recent biopsychosocial theories of anxiety (e.g. Barlow, 1988,1991) underscore the evidence attesting to the ubiquity of panic and anxious apprehension (i.e., worry) across the anxiety disorders. Panic is a phenomenon that is not unique to PD and PDA, but it is evident in all the anxiety disorders as well as the mood disorders (Barlow et al., 1985). Moreover, it is now known that the unexpected nature of panic, previously believed to be a denning characteristic of PD, is in fact not a discriminating feature. For example, unexpected panic plays a role in the etiology of many simple and social phobias, and situational avoidance associated with these disorders may be motivated by the fear of panic and its consequences (McNally & Steketee, 1985; Munjack, 1984; Ost & Hugdahl, 1983). Similarly, inherent to all anxiety disorders is the process of anxious apprehension (Barlow, 1988,1991), denned as a future-oriented mood state (composed primarily of high negative affect) associated with a sense of uncontrollability, and a self-focused attentional shift. In other words, this process denotes a state of persistent overarousal associated with a preparatory and hypervigilant style concerning upcoming negative events that one may not be able to cope with or control. Whereas all DSM-III-R anxiety disorders are characterized by this process, the focus of apprehension varies from disorder to disorder. PD results from emergence of anxious apprehension focused on the possibility of future spontaneous panics; in social phobia, anxiety develops over the possibility of poor performance in social contexts (resulting from panics, performance deficits, etc.). The fact that anxious apprehension is conceptualized in these models as a unifying process of the anxiety disorders bears on the issue of sources of lower diagnostic reliability of GAD. In DSM-III-R, the criteria for GAD were revised such that the disorder had its own key symptom of excessive and unrealistic worry in areas unrelated to another Axis I disorder. Nevertheless, because worry is a central characteristic of anxious apprehension, and anxious apprehension is present to some extent in all anxiety disorders, the distinctiveness of this GAD criterion is diminished. Indeed, factor analyses, using a large sample of anxiety disorder patients (N = 347) and a battery of standardized anxiety measures, found that a validated measure of the trait of worry, although loading more highly on a GAD factor (.46) than on factors corresponding to other DSMIII-R disorders (e.g., OCD, PD, and social phobia), loaded most highly (.69) on a diagnosis-nonspecific general distress factor (Brown, Moras, Zinbarg, & Barlow, 1991). Further adding to the problems with the reliability of the GAD diagnosis, the ratings composing its associated symptom criterion have proven unreliable and of weak discriminant validity in the context of other anxiety disorders (Barlow & Di Nardo, 1991; Borkovec, Shadick, & Hopkins, 1991; Fyer et al, 1989). Finally, another difference between GAD and other anxiety disorders is that many of the other disorders are characterized by outstanding key features that facilitate differential diagnosis (e.g., compulsions in OCD; Barlow & Di Nardo, 1991; Brown et al., 1991).

eluded about the diagnostic reliability of these categories (e.g., kappas are adversely affected by high and low base rates).

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Despite these issues, interest in the GAD diagnosis has increased markedly in recent years with recognition that it may represent the basic anxiety disorder (cf. Barlow, 1988; Rapee, 1991). In other words, the processes (e.g., anxious apprehension) highlighted in the GAD diagnosis may reflect more basic processes that serve as vulnerability factors to the development of a wide variety of emotional disorders (e.g., anxiety disorders, mood disorders, sexual dysfunction; cf. Garvey, Cook, & Noyes, 1988). Recent models of anxiety posit that some of these vulnerability factors emerge on the basis of early life experiences (Barlow, 1988,1991). It is noteworthy, too, that GAD has been conceptualized within the context of an Axis II disorder (Sanderson & Wetzler, 1991).

Implications for DSM-IV Many of the aforementioned issues and findings are evident in the proposed revisions in the diagnostic criteria of the anxiety disorders for DSM-IV. Note that changes in the criteria listed here represent only a selected subset of changes under consideration and may not be the final word because they are subject to further revision pending data from the ongoing field trials. Researchers have acknowledged evidence that panic occurs across the anxiety disorders. Therefore, a revision under consideration is to present the criteria for panic in its own section, prior to listing criteria for the anxiety disorders themselves, rather than within the criterion set of PD. In the case of social phobia and simple phobia (to be renamed specific phobia in DSM-IV), panic and the process of "anxious anticipation" will most likely become part of the revised criterion set. Moreover, these revisions should provide clarification that social and specific phobia may be assigned to reflect a clinical presentation involving unexpected panic attacks, so long as the panics occur only within the context of the circumscribed phobic cue or cues. The criteria for GAD have been revised to highlight further the chronic, pervasive, excessive, and, most important, uncontrollable nature of worry. Efforts are ongoing to make the somatic criterion of GAD more reliable, discriminating, and user-friendly. Also being considered is a new diagnostic category, mixed-anxiety depression, to recognize the potentially large number of individuals whose clinical presentations do not meet full criteria for either an anxiety or mood disorder (cf. Katon & Roy-Byrne, 1991; Zinbarg & Barlow, 1991). This consideration also acknowledges recent theoretical positions (e.g. Barlow, 1988) that consider anxiety and depression (i.e, dysthymia) as largely equivalent constructs sharing common vulnerabilities (cf. Clark & Watson, 1991).

Comorbidity Among DSM-III-R Anxiety Disorders Anxiety and Depressive Disorders With the aforementioned issues in mind, we now turn to recent findings pertaining to the rates of comorbidity among the anxiety disorders, focusing on data derived from the DSMIII-R categories. As previously indicated, when structured interviews that screen for the presence of a range of disorders are used in the evaluation of patients presenting to anxiety disorder

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TIMOTHY A. BROWN AND DAVID H. BARLOW

clinics, multiple disorders are usually uncovered. To illustrate this assertion, we present cross-sectional comorbidity data from a study that was recently completed at the Center for Stress & Anxiety Disorders in Table 2 (Moras et al., 1991). These data were derived from a large sample (N= 468) of carefully diagnosed patients who presented for evaluation, treatment, or both to our anxiety disorders specialty clinic. It is important to note that the ADIS-R, the instrument used for establishing diagnoses, was designed to comprehensively evaluate anxiety, mood, and somatoform disorders (and screen for the presence of other disorders, e.g., psychosis), and thus patterns of comorbidity were largely confined to these types of disorders. Moreover, current and recent (past 6 months) substance abuse was an exclusion criterion in this study. Consistent with previous findings (e.g., de Ruiter et al., 1989; Sanderson, Di Nardo, Rapee, & Barlow, 1990), rates of comorbidity were high. Indeed, 50% of patients with a principal anxiety disorder had at least one clinically significant anxiety or depressive disorder. The principal diagnoses of GAD and PDA (severe) were the categories associated with the highest comorbidity rates, and simple phobia was associated with the lowest. Pertinent to the theoretical considerations outlined above, GAD was the most frequently assigned additional diagnosis at the clinically significant level (23%), followed by social phobia (14%). Also noteworthy are the findings that GAD and social phobia were the most frequently assigned additional diagnoses in a study examining patients with a principal disorder of major depression or dysthymia (Sanderson, Beck, & Beck, 1990). Similarly, GAD was second to substance abuse as the most commonly co-occurring lifetime and current disorder in a large survey of Vietnam war veterans with and without PTSD (Kulka etal., 1990).

Data on the high comorbidity rate involving GAD at both the principal and additional diagnostic level are interesting in light of recent findings that early onset of depression is associated with greater comorbidity (Rohde, Lewinsohn, & Seeley, 1991). As noted above, among the anxiety disorders, GAD has been found to be associated with the earliest onset and has been considered conceptually as a possible characterological disorder (cf. Sanderson & Wetzler, 1991). As suggested earlier, the degree of diagnostic comorbidity is directly related to the thresholds set to determine the presence or absence of various disorders (Frances et al., 1990). Accordingly, when diagnoses of any clinical severity rating were considered in Moras et al. (1991), fully 79% of patients had at least one additional disorder. This latter figure is more comparable to rates (70%) found in a prior study (Sanderson, Di Nardo, Rapee, & Barlow, 1990) that focused on comorbid disorders of any clinical severity. It is also interesting to note that the threshold set for "caseness," in addition to affecting overall comorbidity rates, affected certain comorbid diagnoses more so than others. For instance, Moras et al. found that, when disorders of any clinical severity were considered, comorbidity involving additional diagnoses of simple and social phobia increased markedly, whereas certain diagnoses were relatively unaffected (e.g., OCD and PDA (severe) agoraphobia). This finding suggests that certain features appear to be frequently present at subclinical levels (cf. Rapee, Sanderson, & Barlow, 1988), whereas other features are usually associated with clinically significant distress or impairment. Another striking finding was that most of the anxiety disorders had low comorbidity rates with the mood disorders, with the exception of OCD (40%) and PDA (severe) agoraphobia (55%). In fact, comorbidity rates involving depression were

Table 2 Percentages of Additional Diagnoses Among Anxiety-Disorder Patients DSM-IH-R principal diagnosis Additional diagnoses' Anxiety disorders PD PDA (mild) PDA (mod) PDA (sev) SOC GAD OCD SIM Mood disorders MDE DYS MDE or DYS

PD (n = 35)

PDA (mild) (« = 1 10)

PDA (mod) (n = 76)

PDA (sev)

SOC (« = 76)

GAD (n = 38)

OCD (« = 25)

SIM (n = 25)

MDE ( « = 13)

Overall"

4 4 1 0

18 18 0 0 29

0 12 0 0 24 4

8 15 0 0 23 23 15 0

6 9 1 0 14 23 2 8

0 0

11 9 18

6 •20 3 3

11 36 1 4

12 21 0 8

36 27 9 27

17 1

9

3 16

4

0 4 0 0 0 8 0 8

9 3 11

7 5 12

16 4 18

36 27 55

11 13 20

11 18 29

12 28 40

4 0 4

Note. DSM-IH-R = Diagnostic and Statistical Manual of Mental Disorders (3rd. ed., rev); ADIS-R = Anxiety Disorders Interview Schedule-Revised; PD = panic disorder; PDA (mild) = panic disorder with mild agoraphobia; PDA (mod) = panic disorder with moderate agoraphobia; PDA (sev) = panic disorder with severe agoraphobia; SOC = social phobia; GAD = generalized anxiety disorder; OCD = obsessive-compulsive disorder; SIM = simple phobia; MDE = major depressive episode; DYS = dysthymia. " Additional diagnoses assigned with ADIS-R clinical severity rating of 4 or above. b Overall frequency of each diagnosis as an additional, computed controlling for the number of cases in which it could be assigned as an additional (e.g., SOC could only be assigned as an additional in 409 - 76 = 333 cases, because 76 cases had principal SOC).

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SPECIAL SECTION: ANXIETY DISORDERS

lower in the Moras et al. (1991) study than in several prior studies. However, this is likely attributable to the fact that the prior studies either used lower thresholds (e.g., Sanderson, Di Nardo, Rapee, & Barlow, 1990) or calculated comorbidity rates based on longitudinal or lifetime diagnoses (e.g., Breier, Charney, & Heninger, 1984). Whereas many recent studies focused on cross-sectional Comorbidity, data examining longitudinal rates and the temporal sequence of disorders are important as well. Studies examining the temporal order of comorbid anxiety and depressive disorders have frequently found that anxiety disorders more often precede rather than follow depression (e.g., Alloy, Kelly, Mineka, & Clements, 1990; Breslau, 1990; Rohde et al., 1991; although see Breier et al., 1984). These findings may lend support to recent theories that conceptualize anxiety and depression as similar constructs falling on different points of a helplessnesshopelessness continuum (Alloy et al., 1990; Barlow, 1988,1991). Substance Abuse Disorders Numerous studies have noted a high rate of comorbidity among the anxiety and substance abuse disorders. The majority of these studies have taken the approach of examining the prevalence of anxiety disorders in alcoholic patient samples. Collectively, these studies indicate that the lifetime prevalence of clinically significant anxiety disorders in alcoholics is 25% to 45%, with PDA and social phobia typically noted as the most frequently co-occurring diagnoses (e.g., Bowen, Cipywnyk, DArcy, & Keegan, 1984; Chambless, Cherney, Caputo, & Rheinstein, 1987; Hesselbrock, Meyer, & Keener, 1985). These rates approach 60% when milder forms of anxiety disorders are considered (Mullaney & Trippett, 1979; Smail, Stockwell, Canter, & Hodgson, 1984). Studies examining alcoholism rates in anxiety-disorder outpatient samples indicate that roughly 15% to 25% evidence current or past alcohol abuse or dependence (e.g., Bibb & Chambless, 1986; Thyer et al., 1986). Substance abuse was also the most commonly co-occurring disorder in male Vietnam veterans with PTSD (Kulka et al., 1990). Here again, examination of the temporal sequence of disorders is of importance given the possibility that substance abuse may reflect attempts to self-medicate excessive anxiety or may contribute to the etiology of the anxiety disorders (cf. Kushner, Sher, & Beitman, 1990). Whereas the majority of studies addressing this issue have concluded that anxiety precedes alcohol abuse in most cases (e.g., Chambless et al., 1987; Mullaney & Trippett, 1979; Smail et al., 1984), Kushner et al. noted that this appeared to be the case only with certain disorders (i.e., PDA, social phobia, and simple phobia). For disorders such as PD, OCD, and GAD, these authors noted that temporal order varied considerably. A potential factor contributing to these findings is the observation that the symptoms of PD and GAD are indistinguishable from the symptoms of alcohol withdrawal (Chambless et al., 1987; Stockwell, Smail, Hodgson, & Canter, 1984). Thus, rates of comorbidity may have been inflated somewhat because of overlapping features. On the other hand, reactions to psychoactive substances may contribute to the etiology of anxiety disorders such as PD (Aronson & Craig, 1986). Personality Disorders A growing number of studies have examined rates of diagnostic comorbidity among the anxiety and personality dis-

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orders. To date, the majority of these investigations have focused on patients with PD or PDA. Findings from these studies indicate that 27% to 65% of PD and PDA patients evidence a coexisting personality disorder (Chambless & Renneberg, 1988; Friedman, Shear, & Frances, 1987; Green & Curtis, 1988; Koenigsberg, Kaplan, Gilmore, & Cooper, 1985; Mavissakalian & Hamann, 1986; McCauley, 1991; Reich, Noyes, & Troughton, 1987). In most of these studies (e.g., Green & Curtis, 1988; Mavissakalian & Hamann, 1986; McCauley, 1991; Reich et al., 1987), the majority of assigned comorbid personality disorders represented those from Cluster 3 (anxious/fearful), although conflicting data do exist (e.g., Friedman et al., 1987). Studies examining other anxiety disorders such as GAD (Sanderson & Wetzler, 1991) and OCD (Steketee, 1990) have also found high comorbidity rates with personality disorders (50% in both studies), particularly among those from Cluster 3. In one of the few studies that examined whether the rates of comorbidity of personality disorders were differentially distributed across the DSM-IH-R anxiety disorders, McCauley (1991) administered the Personality Diagnostic Questionnaire —Revised (PDQ; Hyler & Reider, 1987) to a large sample (N= 133) of patients with a principal anxiety disorder. All anxiety disorder diagnoses were represented with the exception of PTSD. Results indicated that rates of comorbid personality disorders did not differ significantly among the anxiety disorders. However, unlike McCauley (1991), who collapsed across levels of agoraphobic avoidance in the PD group, Friedman et al. (1987) found that personality disorder comorbidity rates increased with the extent of avoidance. In a study evaluating the impact of having a coexisting personality disorder on clinical presentation of anxiety disorder patients, Klass, Di Nardo, and Barlow (1989) found that patients with comorbid personality disorders were three to four times more likely to evidence current dysthymia than were anxiety patients without a comorbid personality disorder. In addition, these patients were significantly more likely to have had a past major depressive episode. When interpreting these data, several considerations should be kept in mind. For instance, as is the case with studies involving the DSM-HIand DSM-IH-R personality disorders in general, the reliability (e.g., interrater) of the diagnoses was rarely examined. Moreover, the instruments and approaches to assessment (i.e., interviews and questionnaires) used for establishing these diagnoses varied considerably. It is interesting to note that, despite speculations to the contrary (e.g., Chambless & Renneberg, 1988), questionnaire-based assessment did not result in a higher incidence of personality disorder diagnoses than did interview-based assessments in these studies; in fact, the lowest rate (27%) was obtained by Mavissakalian and Hamann (1986), using the PDQ. In addition, whereas the personality disorders have been criticized for the substantial overlap among their diagnostic criteria across categories (cf. Frances et al., 1990), many of these criteria appear to overlap the diagnostic features of the anxiety disorders as well. This point may be particularly salient to the interpretation of findings indicating a high coexistence of Cluster 3 disorders among principal anxiety disorders. Such co-occurrence may speak to the limitations inherent in the extant diagnostic criteria and point to the fact that, despite the assumption in DSM-IH-R of qualitative distinctiveness of Axis I and Axis II disorders, these disorders may

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operate along common dimensions with differences being primarily of chronicity or severity (cf. social phobia and avoidant personality; Widiger & Shea, 1991). Nevertheless, these data may also have bearing on the position that these traits serve as a vulnerability factor toward the development of other emotional disorders. However, in future studies, temporal sequence should be examined more closely to address the alternative possibility that these characteristics, in some instances, may emerge after the onset of an Axis I disorder (e.g., emergence of dependent features in a severely agoraphobic patient).

Implications of Comorbidity for Treatment The past decade has witnessed substantial advances in the development and evaluation of psychosocial (i.e., cognitive-behavioral) treatments for anxiety disorders. For virtually all of the DSM-HI-R anxiety disorders, there now exist controlled studies illustrating the efficacy of these new treatments. In the case of some disorders (e.g., PD and PDA), these treatments have been compared with the leading pharmacological treatments (e.g., alprazolam and imipramine) and have been found to be of equal or greater effectiveness, particularly over the posttreatment follow-up phase. For example, whereas in a direct comparison of alprazolam (AZ) and cognitive-behavioral therapy (CBT) for PD, panic-free rates at posttreatment did not differ significantly (AZ = 50% and CBT = 87%; Klosko, Barlow, Tassinari, & Cerny, 1990), relapse rates associated with AZ discontinuation have generally been in the range of 90% (Fyer, 1988; Mellman & Uhde, 1986; Pecknold, Swinson, Kuch, & Lewis, 1988). In contrast, the majority of follow-up studies involving cognitive-behavioral treatments of PD have shown that patients tend to maintain or improve on the gains achieved by posttreatment (cf. Brown & Barlow, in press; Michelson & Marchione, 1991). Indeed, long-term follow-up results, from three recently completed studies examining the efficacy of cognitive-behavioral treatments of PD, noted panic-free rates in the range of 80% at these assessment periods (see Margraf, Barlow, Clark, & Telch, in press, for a review of these studies). At the heart of cognitive-behavioral treatments for anxiety disorders is the provision of some form of therapeutic exposure to anxiety-provoking situations, either external or internal. In addition, most approaches involve some form of cognitive restructuring as well. Despite these two commonalities, therapeutic techniques derived for each disorder tend to be quite specific (see Brown, Hertz, & Barlow, 1992, for a review of recent advances in the psychosocial treatment of anxiety disorders). Although practitioners have long used clinical judgment in adjusting or deciding on which treatments to deliver on the basis of coexisting conditions (e.g., caution in recommending certain medications to patients presenting with suicidality or substance abuse), very seldom has this decision making been data driven. As will be evident later in this article, few of the studies examining the efficacy of treatments for anxiety disorders have evaluated the presence and impact of comorbid disorders. Moreover, data bearing on the issue of how these treatments can be adjusted in light of comorbid conditions are virtually nonexistent. This is due partially to the fact that, for many disorders (e.g., GAD), effective treatments have been de-

veloped only recently (Barlow, Craske, & O'Leary, 1991). Furthermore, the presence of certain commonly occurring comorbid conditions (e.g., depression and substance abuse) is often part of the exclusionary criteria in many outcome studies. The aforementioned findings attesting to the vast prevalence and range of comorbid diagnoses highlight the fact that researchers have overlooked a factor that may have substantial implications for the conclusions drawn regarding treatment efficacy. On the basis of these data, it is apparent that for certain diagnoses (e.g., PDA and GAD), comorbidity is more apt than others to be an issue warranting treatment consideration (e.g., simple phobia). Inclusion of patients into treatment studies on the basis of a given principal diagnosis, without consideration of comorbid diagnoses, may give the illusion of sample homogeneity when, in fact, the sample is quite heterogeneous. By not acknowledging this source of sample heterogeneity (as well as numerous other sources of variability such as the use of medications), important information regarding the effects of treatment may be lost. Along these lines, issues awaiting future research include the following: (a) Does the presence of certain comorbid disorders or symptoms affect the short- and longterm response to treatment? (b) What types of adjustments should and can be made to extant treatments to enhance treatment efficacy when comorbidity is present? (c) What is the course of comorbid disorders and symptoms after successful treatment of the principal disorder? Although data are quite sparse on the issue of how comorbidity affects treatment outcome and the long-term course of anxiety disorders, some data do exist regarding comorbid patterns involving depression and personality disorders. For instance, findings suggest that PD patients with comorbid major depression display greater psychopathology (Coryell et al., 1988; Lesser et al., 1988), are less likely to respond to "conventional antidepressants" (Grunhaus, 1988) and placebo therapy (Coryell & Noyes, 1988), and are less likely to recover over a 2-year period than are PD patients without major depression (Coryell et al., 1988). Regarding behavioral treatment of OCD, whereas early studies (e.g., Foa, Grayson, & Steketee, 1982) indicated that depression was associated with less favorable improvement and greater likelihood of relapse, more recent studies have not corroborated this relation (e.g., Basoglu, Lax, Kasvikis, & Marks, 1988; Foa, Steketee, Kozak, & McCarthy, 1990). Studies examining the impact of co-occurring personality disorders have produced data suggesting that this variable may predict poor response to behavioral treatment of social phobia (Turner, 1987) and to pharmacological and "naturalistic" treatment of PD and PDA (Green & Curtis, 1988; Mavissakalian & Hamann, 1987; Noyes et al., 1990; Reich, 1988). In addition, comorbidity may have implications for the standards used in evaluating the extent to which treatment is effective. For example, in anxiety treatment outcome research, it has become common practice to develop composite indices of endstate functioning to reflect the percentage of patients evidencing clinically significant response to treatment (Barlow, 1989; Jacobson, Wilson, & Tupper, 1988). As part of satisfying criteria for achieving high end-state functioning status, most studies specify that patients must score low (or below clinical range) on measures of general anxiety (e.g., Hamilton scales). However, these criteria are applied without consideration of the impact of untreated coexisting conditions. Thus, this may provide an

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SPECIAL SECTION: ANXIETY DISORDERS

overly stringent test of treatment efficacy because posttreatment levels of symptomatology are likely to be, in part, due to comorbid conditions. A potentially very useful alternative approach to examining the impact of comorbidity at the diagnostic level is to develop and evaluate the utility of dimensional approaches of measurement of various symptoms that appear to be either key features (i.e., essential or denning symptoms such as compulsions) or common features (e.g., negative affect) of the anxiety disorders (Di Nardo & Barlow, 1990; Frances et al., 1990; Moras & Barlow, 1992). Such an approach would produce diagnostic profiles (i.e., plots of scores across dimensions) that may facilitate a variety of endeavors including the identification of (a) symptoms or symptom patterns that predict response to treatment or the course of disorder and (b) symptoms that are responsive or resilient to extant psychosocial and pharmacological treatments. For example, although the majority of patients with PD do not present with a comorbid diagnosis of hypochondriasis, a large number do evidence features of this disorder (e.g., fear or belief that panics may produce stroke or heart disease). Just as overvalued ideation may be a predictor of treatment response in OCD (Foa & Kozak, 1989), the extent of belief conviction on the part of PD patients' perceptions of the consequences of anxiety may be associated with outcome as well. A dimensional approach to assessment would allow for such an analysis. Nevertheless, because this approach would be concerned with assessment at the symptom rather than syndrome level, the psychometric properties (e.g., discriminant validity) of the measures used to assess these features would become an issue of even greater importance. For example, very few symptoms consistently distinguish anxious from depressed patients (Clark & Watson, 1991). Given findings of this nature, in tandem with the considerable overlap in items contained in commonly used measures of anxiety and depression (cf. Kendall & Watson, 1989), the utility of the dimensional approach will be largely related to the extent psychometrically sound measures of the features comprising the dimensions (particularly of key features) are developed. Another avenue for future research is to examine the impact a specific treatment has on the symptomatology of co-occurring disorders not targeted as part of treatment. Whereas the obvious first step would be to examine whether, in fact, treatment produces symptom reduction in comorbid conditions, another important step would be to evaluate the mechanism (or mechanisms) responsible for this reduction, if noted. For example, corresponding reductions in untargeted comorbid disorders may be reflective of poor discriminant validity (i.e., overlap) among diagnostic categories. Conversely, comorbid conditions that remain relatively unaffected by the successful treatment of another disorder would provide data in support of the distinctiveness of the categories. In a series of studies conducted by Mavissakalian and his colleagues (Mavissakalian & Hamann, 1987; Mavissakalian, Hamann, & Jones, 1990), antidepressant and combined antidepressant/behavioral treatment was found to produce substantial reductions in personality disorder symptomatology (e.g., number of diagnoses assigned and personality trait scores) in patients with OCD and PDA. These data may speak to the overlap evident in features comprising these disorders. A second potential mechanism accounting for reduction in

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comorbid symptomatology is treatment generalization. With respect to this process, a potentially important factor in comparing the effectiveness of treatments would be consideration of whether treatments differentially promote reductions in symptomatology in comorbid conditions or whether a particular type of treatment is more likely than another to retain its effectiveness when coexisting conditions are present. For purposes of this article, we analyzed a subset of the data from a study nearing completion at the Center for Stress & Anxiety Disorders that is examining the comparative efficacy of several components (i.e., cognitive restructuring, breathing retraining, and interoceptive exposure) in the treatment of PD (Barlow, Brown, Craske, Rapee, & Antony, 1991). As part of the previously mentioned study nearing completion, data (ADISR) regarding the presence and clinical severity of additional diagnoses are being collected at pre- and posttreatment and at all follow-up assessments. To address many of the aforementioned points, we analyzed the impact that treatment had on the comorbid diagnosis of GAD, because prior studies found this to be the most frequently co-occurring diagnosis in patients with a principal diagnosis of PD (e.g., Moras et al., 1991). GAD, both at the clinical level (i.e., ADIS-R clinical severity rating of 4 or above) and subclinical level, was considered. As can be seen in Figure 1, of the 68 treated PD patients considered, 32% had a clinically significant GAD additional diagnosis at pretreatment; an additional 9% evidenced subthreshold GAD. Interestingly, at posttreatment the rate of threshold GAD declined to 9%; subthreshold GAD increased to 16% because a few patients with a clinically significant GAD at pretreatment moved to the subclinical category at posttreatment. These posttreatment breakdowns remained relatively stable at the 3-month follow-up. Whereas these findings are noteworthy in that they suggest that GAD declines with treatment of PD, particularly in light of assertions that GAD represents one of the more characterological anxiety disorders (e.g., Sanderson & Wetzler, 1991), the mechanism, or mechanisms, accounting for this phenomenon is not clear. First, as noted previously, one possible mechanism is treatment generalization. In our study, all treatment conditions had a cognitive restructuring element. Given that cognitive techniques have been found to be effective in the treatment of GAD (e.g., Butler, Fennell, Robson, & Gelder, 1991), patients may have efficaciously applied these skills to their chronic, nonpanic-related worries. To address this issue further, it would be interesting to examine the impact that PD treatment has on comorbid GAD using a treatment package composed of elements presumed not to be salient to the treatment of GAD. Second, the reduction in comorbid GAD may be reflective of overlapping features in the criteria that compose PD and GAD. On this basis, the rates of GAD may have declined at posttreatment because the PD treatments successfully resolved patients' persistent overarousal and thus made it less likely that they would meet the somatic criterion of GAD. Similarly, bearing on the issue of the discriminant validity and diagnostic reliability of the diagnosis (cf. Di Nardo et al., in press), GAD spheres of worry identified at pretreatment may have, in fact, been functionally related to, or secondary to, PD symptomatology (e.g., a sphere identified as "fear of poor job performance" may be due to a worry that panics may result in vocational interference). Finally, certain methodological factors may contribute to re-

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CLINICAL GAD

NO GAD

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E3 SUBCLINICAL GAD

PRE-TX

POST-TX

3 MO. FU

TREATMENT PHASE Figure 1. Effects of panic control treatment on comorbid generalized anxiety disorder (GAD) diagnoses in 68 patients with panic disorder. (Clinical GAD = Anxiety Disorders Interview Schedule—Revised [ADIS-R] diagnosis of GAD with clinical severity rating of 4 or above on a 0-8 scale; subclinical GAD = ADIS-R diagnosis of GAD with clinical severity rating below 4; PRE-TX = before treatment; POSTTX = after treatment; and 3 MO. FU = 3 month follow-up.)

ductions in comorbid symptomatology at posttreatment as well (e.g., nonspecific demands on either the clinician to not assign a diagnosis or the patient to present nonsymptomatically).

Conclusion Inevitably, this article presents more of a research agenda than a fait accompli data set. Only since 1987, with the publication of the DSM-IH-R, has the importance of ascertaining patterns of comorbidity been widely recognized. However, data on comorbidity have fundamental significance. As is evident in this article, most research to date is at the level of descriptive comorbidity (e.g., Moras et al., 1991). Yet to come are important studies on the impact of comorbidity on treatment outcome and classification. These studies will most likely illuminate the nature of psychopathology in emotional disorders and point to the incorporation of some dimensional scaling of psychopathological features into the nosology. Such findings may ultimately support the position advanced in this article that both syndrome and symptom comorbidity can have a substantial impact on the course of the principal disorder and its treatment (i.e., certain psychopathological features, although not forming a separate diagnostic entity, affect the course of a disorder and its treatment response). DSM-IVhas come too quickly on the heels of DSM-III-R for research on comorbidity to have had such an impact. With the 12- to 15-year lag anticipated before the appearance of DSM-V, data on comorbidity, and the conceptual advances that will emanate from these data, should profoundly affect the clinical science.

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