comparing panic disorder uncomplicated and panic disorder with agoraphobia in cardiology patients...

Journul ofilnrieiy Disordcvs. Vol. I. pp. 301-312. 1987 F’nnred in the USA. All n&s reserwd.

08x7-6185: 53 a, * .oo Copyright 0 1987 Pergmon Journals Ltd.

Comparing Panic Disorder Uncomplicated and Panic Disorder Agoraphobia in Cardiology Patients

with with

Atypical or Nonanginal Chest Pain

BERNARD D. BEITMAN, M.D.,* IMAD M. BASHA, M.D., LORI DEROSEAR, D.O., GREG FLAKER, M.D., AND

VASKAR MUKERJI, M.D.

University of Missouri-Columbia Health Sciences Center

Abstract-Thirty-eight cardiology patients with either atypical or nonanginal chest pain and current panic disorder were divided into two groups. those with agoraphobia (N = 8) and those without agoraphobia (N = 30). The agoraphobia group reported marginally longer duration of panic disorder (17.0 2 21.1 years vs. 3.0 2 3.2 years) and significantly more panic symptoms (10.6 i 3 vs. 7.3 r 2.2) during the last major attack. The agoraphobia group also scored significantly higher on measures of anxiety, depression, phobic avoidance, somatization, interpersonal sensitivity, and psychoticism and also scored higher on three of three global measures of distress. This agoraphobia group differed from previously reported agoraphobics with panic attacks in that they all had current panic disorder, while previously reported groups were categorized according to DS,Ll-III, which required only a history of panic attacks. These findings suggest that patients who have current panic disorder and agoraphobia are more symptomatic. Of interest is the low proportion of agoraphobics compared to nonagoraphobics found in this panic disorder population.

The proposed revisions to DSM-III (Work group to revise DSM-III, 1985) have placed agoraphobia within the panic disorder spectrum rather than leave it as a separate diagnostic entity, because in the majority of agoraphobia cases, panic attacks appear to have preceded the development of phobic avoidance. (American Psychiatric Association, 1980; Thyer, Himle, Curtis, Cameron, & Nesse, 1985). Furthermore, the proposed revisions take into consideration the clinical reality that many agoraphobics do not present with an extreme degree of phobic avoidance

* Address correspondence and reprint requests to of Psychiatry, University of Missouri-Columbia lumbia, MO 65212.

Bernard D. Beitman, h1.D.. Department Health Sciences Center, Clinic 6, Co-

301

302 B. D. BEITMAN ET AL.

but instead fall along a mild to severe continuum (Work group to revise DSM-III, 1985).

Do patients with agoraphobic symptoms differ in critical ways from those with uncomplicated panic disorder in addition to their phobic avoidance? Thyer et al. (1985) compared 40 subjects randomly selected from the patient files of an anxiety disorders program, 20 of whom had panic disorder and 20 of whom had agoraphobia with panic attacks as defined by DSM-III. Comparison of demographic, psychometric and clinical features of the two groups revealed few differences. Agora- phobics scored higher only on ratings of interpersonal sensitivity, phobic anxiety, paranoid ideation, and alcohol use. In a study of the phenomena of panic, Barlow, Vermilyea, Blanchard, Vermilyea, DiNardo, and Cerny (198.5) found no significant differences between the panic experienced by agoraphobics and the panic experienced by subjects with panic disorder uncomplicated as defined by DSM-III criteria. The two groups also did not differ on the average number of panic symptoms and the average severity of symptoms. Noyes, Crowe, Harris, Hamra, McChesney, and Chaudry (1986) reported that when agoraphobics (N = 40) were compared to persons with panic disorder (N = 40) probands and relatives with agoraphobia reported an earlier onset of illness, more persistent and disabling symptoms, more frequent complications and a less favorable outcome than probands and relatives with panic disorder. They con- cluded that agoraphobia might be a more severe variant of panic disorder.

We undertook to examine this question by comparing subjects with panic disorder uncomplicated and subjects having panic disorder with agoraphobia who were identified from an outpatient cardiology clinic. In two previous publications in the Journal we have suggested that cardiology patients with chest pain and without evidence of coronary artery disease are likely to have panic disorder. In the first article (Mukerji, Beitman, Alpert, Hewett & Basha, 1987), we reported a retrospective chart review suggesting a high prevalence of panic attacks in patients with chest pain and angiographically normal coronary arteries. This finding was subsequently substantiated by a prospective pilot study (Beitman, Lamberti, Mukerji, DeRosear, Basha, & Schmid, in press). In the second Journal article (Beitman, DeRosear, Basha, Flaker, & Cor- coran, 1987), we found preliminary evidence that cardiology outpatients with either atypical or nonanginal chest pain had a higher likelihood of having panic disorder. This pilot study (N = 30) has now been extended to 104 subjects, the data from which substantiate the early finding, namely that more than 40% of cardiology patients with either atypical or nonanginal chest pain and no coronary artery disease have panic disorder. Detailed comparisons of the groups within the 104 subjects will be reported elsewhere. In another report we have described differences among the 43 panic disorder subjects from that study with and without major depression (Beitman, Basha, Flaker, DeRosear, Mujkerji, & Lam- berti, in press). In this report, we describe differences between those

PANIC DISORDER AND AGORAPHOBIA IN CARDIOLOGY PATIENTS 303

subjects with and those without agoraphobia in the 43 with panic disorder.

METHODS

Subjects

Forty-three of 104 cardiology patients with either atypical or nonanginal chest pain were identified as having panic disorder (38 current, 5 past) as part of a prevalence study of panic disorder in cardiology patients. Typical angina was defined as substernal pressure, exertional and relieved by rest and/or nitroglycerin. Atypical angina was defined as having but two of these three features and nonanginal chest pain as having but one. These chest pain categories were selected because they are correlated with relatively low probabilities of coronary arter disease compared to typical angina (Diamond & Forrester, 1979; Diamond et al., 1979) and because panic disorder was a possible explanation of the chest pain (Beitman, De Rosear et al., 1987; DaCosta, 1871; White & Jones, 1928; Wood, 1941).

Subjects were referred by cardiologists from an outpatient university hospital cardiology clinic. The sociodemographic characteristics of the sample at the time of interview were as follows: (a) 33 women, 10 men; (b) aged 42.5 + 18.5 years (mean t SD); (c) 28 married, 2 separated, 4 divorced/annulled, 7 widowed, 2 never married. Thirteen had atypical angina, 20 had nonanginal pain, and 1 reported experiencing one or the other type at different times. Coronary artery disease had been ruled out in all 43 subjects by the standard cardiology screening techniques including coronary arteriography, exercise tolerance tests, echocardiog- raphy, and electrocardiograms utilized at the discretion of the consulting cardiologists.

Psychiatric Interview

The Structured Clinical Interview for DSM-III was developed by Spitzer and Williams (1981) to approximate standard psychiatric inter- viewing while retaining sufficient structure to maintain interrater reliability. The SCID-UP (Spitzer & Williams, 1983) was specifically developed for the diagnosis of panic disorder, phobic avoidance (agoraphobia), social phobia, and simple phobia. It also provides major depression diagnoses. To receive a diagnosis of panic disorder, subjects are required to meet revised DSM-III criteria for panic disorder (Work group to revise DSM-III, 1985) and to have at least one panic attack per week for the past three weeks. Phobic avoidance was defined by three subtypes based on the extent of phobic avoidance during the worst period in the three months preceding the interview: (a) Panic Disorder-Uncomplicated, (no significant avoidance); (b) Panic Disorder with limited Phobic Avoidance,


(significant phobic avoidance or endurance of dread, but less than extensive phobic avoidance): (c) Panic Disorder with Extensive Phobic Avoid- ance (generalized travel restrictions, often needs a companion away from home, or markedly altered lifestyle). If not obvious from the overview early in the interview, each subject with panic disorder was asked: “Are there situations or places that you avoid because you are afraid you might have an attack?” If the response was not clear they were asked about: (a) things they avoid or must force themselves to do; (b) going out of the house alone, being in crowds or certain public places like tunnels, bridges, buses, or trains; (c) how often they leave the house alone; (d) how often they need a companion; and (e) the effect avoiding situations or places has on their lives. From this information the interviewer rated the extent of phobic avoidance: none, moderate, or severe.

Interviews were performed by one of two fully trained clinical psychi- atrists. Nine subjects were seen by both interviewers. There was 100% agreement in their ratings of panic disorder, social phobia, simple phobia, and major depression.

Self-Report Questionnaires

Each participant was asked to complete the following questionnaires at the time of the interview: (a) the Zung Self-rating Anxiety Scale (SAS) (Zung, 1971), (b) the Beck Depression Inventory (BDI) (Beck, Ward, Mendelson, & Erbaugh, 1961), (c) the Marks-Mathews Fear Question- naire (Marks & Mathews, 1979), and (d) the Brief Symptom Inventory (BSI) (Derogatis & Melisaratos, 1983).

The SAS measures the current intensity of 20 anxiety symptoms scored on a l-4 severity scale. The BDI measures current levels of 21 depressive symptoms on a O-3 severity scale. The Fear Questionnaire yields scores on three categories of clinical phobias: agoraphobia, social phobia, and blood-injury phobia. Each category is represented by five items rated on a O-8 scale of severity. The BSI is a 53 item inventory reflecting nine primary symptom dimenions. In addition it includes three global indices of distress. The General Severity Index (GSI) is determined by adding up the total symptom score (each of the 53 items is rated O-4) and dividing by 53. The Positive Symptom Total (PST) is calculated by counting all the “positive” (non-zero) symptom responses. The Posi- tive Symptom Index (PSI), a pure intensity measure, is determined by dividing the total symptom score by the PST.

The SAS offers an accepted measure of anxiety. Ten of its 20 items are symptoms of panic attacks. Because depression is commonly found in panic disorder patients (Breier, Charney, & Heninger, 1984) the BDI provided a measure of this symptom complex. The agoraphobia subscale of the Fear Questionnaire could serve to further define the panic disorder group and offer another agoraphobia measure. The BSI provided sub- scales of anxiety, depression, and phobic anxiety by which to test the

PANIC DISORDER AND ~G0MpH0Bl.k IN CARDIOLOGY PATIENTS 305

reliability of the other scales as well as a subscale for somatization. another symptom dimension commonly found in panic disorder patients (Noyes, Reich et al., 1986). The BSI provided the General Severity Index (GSI) to be used as a single summary measure of current distress levels as well as two other global distress indices.

Statistical Methods

To evaluate the relationship between the interview diagnosis of panic disorder and categorical variables (e.g., sex, other psychiatric diagnoses) chi-square tests were used. Continuous variables (e.g., mean group differences in age and the self-report questionnaire scores) were evaluated using the two-tailed student’s t-test. Statistical Analysis System software was used for the data analysis.

RESULTS

Six of the 38 subjects with current panic disorder reported limited phobic avoidance and two reported extensive phobic avoidance. Eight (21%) therefore had some agoraphobic symptoms. Table 1 describes the demographic variables of the 38 subjects with current panic disorder divided into two groups: those with and those without phobic avoidance. The two groups did not differ in regard to age, sex, marital status, or social class (Weiss, 1985).

Table 2 compares the two groups on panic attack measures and prevalence of major depression. They did differ significantly in the number of panic symptoms during the last major attack (t = 4.08, df = 36, p < .OOl) but did not differ in age of onset, number of panic attacks in the week preceding interview, prevalence of current major depression, or reporting

TABLE I DEMOGRAPHIC VARIABLES OF SUBJECTS WITH AND WITHOUT AGORAPHOBIA

With Phobic Without Phobic Avoidance Avoidance (IV = 8) (iv = 30)

Age (SD) Female Married Social Class

I, II, III, IV v, VI, VII, VIII, IX

N

48.0 (21.0)

7 5

I’ 6

(%)

(88) (62)

(12) (75)

IV

42.8 (19.0) 24 18

1** 18

(52)

(80) (60)

(23) (60)

* I not determined. l ‘5 nor determined.

306 B. D. BEITMAN ETAL.

TABLE 2 COMPARISON BETWEEN GROUPS WITH AND WITHOUT AGORAPHOBIA ON PANIC ATTACK

MEASURES AND DEPRESSION DIAGNOSIS

Age of onset (years) Panic attacks during week

preceding interview Duration of panic disorder Panic Symptoms (last major

attack) Current major depression

Past major depression

With Phobic Without Phobic Avoidance Avoidance

(IV = 8) (IV = 32)

x (SD) x LSD)

31.0 (17.6) 39.4 (19.1)

4.4 (4.3) 8.9 (16.1) 17.0 (21.2) 3.0 (3.2)

10.6 (1.3) 7.3 (2.2, 3 5

(38%) (16%) 5 10

(62%) (31%)

at least one episode of past major depression. They differed marginally in duration of panic disorder (r = 1.86, df = 7.1, p < .lO).

On all self-report measures the agoraphobia group scored higher than the group without phobic avoidance.

Table 3 contains the means (-c SD) of the two groups on the self-report questionnaires. The two groups differed significantly on both depression measures (BDI: t = 2.63, df = 36,~ < .Ol); BSI depression: (t = 2.61, df = 36, p < .Ol), both anxiety measures (SAS: t = 2.38, df = 36, p < .Oj); BSI Anxiety: (t = 3.53, df = 36, p < .OOl); agoraphobia (t = 4.21, df = 36, p < .OOl), and phobic anxiety (t = 5.47, df = 36, p < .OOl), as well as social phobia (t = 2.06, df = 36, p = .05) and Fear Questionnnaire total score (t = 3.30, p < .005). They also differed significantly on the following BSI scales: somatization (t = 2.20, df = 36, p = .OS); interpersonal sensitivity (t = 2.28, df = 36, p < .05); psychoticism (t = 2.64, df = 36, p < .Ol); general severity index (t = 3.49, df = 36, p < .OOl); positive symptom distribution index (t = 2.64, df = 36, p < .Ol); and the positive symptom total (t = 2.99, df = 36, p < .005). They differed marginally on the BSI obsessive-compulsive scale (t = 1.86, df = 36, p < .OS); the BSI hostility scale (t = 1.94: df = 36, p < .06); and the Fear Questionnaire social phobia scale (t = 1.85, df = 36, p < .06).

Table 4 shows the comparison of the two groups on the individual items of the fear questionnaire. The items providing the highest scores on the agoraphobia scale were “travelling alone by bus or coach” (t = 4.045, df = 36, p < .OOl) and “going alone far from home” (t = 3.86, df = 36, p < .OOl). The two marginally significant items on the agoraphobia scale were “walking alone in busy streets (t = 1.84, df = 36, p < .08) and “going into crowded shops” (t = 1.98, df = 36, p < .08). On the social phobia scale, “being criticized” was significantly different (t = 2.28, df

PANIC DISORDERANDAGORAPHOBIA INCARDLOLOGY P.ATIENTS 307

T.\BLE 3 CO~~PA~USONBETWEENSUBJECTSWITHASDWITHOUTAGORAPHOBIAON

SELF-REPORTQUESTIONNAIRES

With Phobic Avoidance

(.V = 8) Score (SD)

Without Phobic Avoidance (‘L’ = 30)

Score (SD)

Beck Depression Inventory* Zung Self-Rated Anxiety Scale* Fear Questionnaire

Agoraphobia** Blood Injury Social Phobia* Fear Questionnaire Total*”

Brief Symptom Inventory Somatization’ Obsessive-Compulsive Interpersonal Sensitivity* Depression* Anxiety** Hostility Phobic Anxiety’* Paranoid Ideation Psychoticism” General Severity Index”* Positive Symptom Distribution’ Positive Symptom Total**

21.8 (8.9) 58.5 (7.0)

20.6 (9.6) 7.1 17.0 (10.1) II.3 18.2 (8.6) 11.1 55.9 (23.1) 30.6

2.09 I.54 1.56 I.50 2.08 I.18 I .88 I .05 I.18 1.60 2.13

39.12

(0.75) 1 .S8 (0.72) 1.00 (0.83) 0.88 (0.71) 0.68 (0.88) 0.97 (0.89) 0.68 (0.85) 0.41 (0.65) 0.79 (0.81) 0.43 (0.60) 0.86 lO.45) I .66 (9.36) 26. I3

Il.5 50.8

( 10.0) (11.1)

(7.6) (9.5) (7.2)

(10.1)

(0.53) (0.73) (0.73) (0.80) 10.77) (0.56) (0.60) (0.71) (0.69) (0.52) (0.45)

I I t.26)

*p c .05. **p < 01.

= 36, p < .05). On the blood/injury scale, the two marginally significant items were “thought of injury or illness” (t = 1.84, df = 36. p < .07) and “going to the dentist” (t = 1.84, df = 36, p < .07).

DISCUSSION

These results suggest that subjects with both panic disorder and agoraphobia are more symptomatic on a number of dimensions than persons with panic disorder alone.

The subjects with and without agoraphobia do not differ in sociodemographic data, on prevalence of current or past major depression, or number of attacks in the week preceding the interview. They differed marginally in the duration of panic disorder and significantly in the number of panic symptoms during the last major attack. They also differed significantly on a number of self-report scales including both the SAS and the BSI anxiety scales, the BDI and BSI depression scales and, as expected, on the agoraphobia scale of the Fear Questionnaire and the phobic anxiety scale of the BSI. The agoraphobics also scored signifi-

308 B. D. BERMAN ETAL

TABLE 4 COMPARISONBETWEENGROUPSWITHANDWITHOUTPHOBLCAVO~DANCEOE;INDIVIDUAL

ITEMSOFTHE FEARQUESTIONNAIRE

With Phobic Without Phobic Avoidance Avoidance t:v = 8) (iv = 30)

4 (SD) ? (SD)

Agoraphobia Scale Travelling alone by bus or coach”” Walking alone in busy streets Going into crowded shops Going alone far from home** Large open spaces

Blood/Injury Scale Injections or minor surgery Hospitals Sight of blood Thought of injury or illness Going to the dentist

Social Phobia Scale Eating or drinking with other people Being watched or stared at Talking to people in authority Being criticized* Speaking or acting to an audience

4.74 (2.76) I .43 (1.85) 3.75 (3. IO) 1.67 (2.77) 3.38 (3.07) I.17 (1.46) 5.75 (2.50) 7.07 (2.38) 2.63 (3.42) 0.80 (1.86)

3.00 (2.56) 2.12 (‘.7jl I .75 (2.50) 5.38 (2.44) 4.75 (3.99)

I .Q

3.38 7 7j _.-

5.00

6.00

(1.30) 0.93 (1.69) (2.39) 2.40 (2.30) (2.88) 2.73 (2.10) (2.88) 2.73 (2.40) (3.07) 4.10 (2.88)

I .90 (2.67) 2.07 (2.66) 1.57 (1.22) 3.33 (2.86) 2.43 (2.93)

* p < .Oj. **p < .Ol

cantly higher on the somatization, interpersonal sensitivity, and psychoticism scales of the BSI, as well as all three BSI global indices of distress.

That this group of panic disorder patients found in a cardiology clinic may be similar to psychiatric panic disorder patients is suggested by data from a pilot medication trial. Ten cardiology patients with panic disorder and without evidence of coronary artery disease entered an eight week, open label trial of alprazolam. Seven of the 10 met criteria for a positive response (a 50% or greater reduction of panic frequency between base- line and Week 8) (Beitman, Basha, Trombka, Jayaratna, & Russell, 1987).

Unlike the findings of Thyer et al. (1985), who found elevated scores on only the phobic anxiety, interpersonal sensitivity, and paranoid ideation scales of the SCL-90, this study of cardiology patients with panic disorder suggests that agoraphobics with panic disorder differ significantly from those with panic disorder alone on many dimensions. In addition to expected elevations in the phobic anxiety measures they reported more anxiety, more depression, more somatization, more interpersonal sensitivity, and more psychoticism. Also striking is their significant elevation on the global indices of distress. In this study sub-


jects with both panic disorder and agoraphobia are clearly more symptomatic than those with panic disorder alone.

The BSI results may be compared to the SCL-90 results because there is a high correlation between the scales of the two instruments (Derogatis & Melisaratos, 1983). In fact, the BSI was derived from the SCL-90 to provide a briefer means to gain similar information. Why the difference in the two studies? In addition to being samples of different populations (e.g., patients seeking help from an anxiety disorders clinic, vs. cardiology patients with chest pain) the groups differed diagnostically. Thyer et al. (1985) used DSM-III which required agoraphobic symptoms and only a past history of panic attacks for the diagnosis of agoraphobia with panic attacks. Unlike the cardiology group, these patients were not required to be experiencing current panic attacks at the frequency of at least three in the previous three weeks. The agoraphobics in the cardiology group were experiencing both disorders concurrently, while in Thyer et al. (198.5) at least some of the agoraphobics were likely not to be experiencing a current panic disorder. The groups in the two studies were, therefore, not equally constituted. Aside from the expected significant difference in phobic anxiety, the two studies did find agreement on the interpersonal sensitivity scale. Perhaps this similarity deserves further investigation.

On the fear questionnaire agoraphobia scale, the items differentiating agoraphobics were “travelling alone by bus or coach” and “going alone far from home.” For this group, as opposed to the British population from which the Fear Questionnaire was drawn, it would appear that these two items correlate most highly with phobic avoidance. Perhaps “busy streets” and “crowded shops” are of less concern since the University Hospital is located in a relatively small city and many of its patients come from smaller towns where “crowded shops” and “busy streets” are relatively uncommon. The significant difference on the social phobia item “being criticized” supports the general observation that agoraphobics are afraid of what others will think about them.

Of interest here as well, is the relatively low percentage of agoraphobics 8/38 (21%) found in this sample compared to reports from anxiety disorders clinics. The percentage of patients having agoraphobia with panic attacks from samples containing both agoraphobia with panic attacks and panic disorder were reported by the following authors to be: Thyer et al. (1985) 621157 (40%), Breier et al. (1984) 42/60 (70%), Noyes, Reich et al. (1986) 55/60 (920/o), and Barlow (personal communication, 1986) 481.50 (98%). Uhde, Boulenger, Roy-Byrne, Geraci, ViHone, and Post (1985) reported that 32 of 38 (84%) subjects with panic disorder had agoraphobia.

There are two reasons why these cardiology patients with chest pain and panic disorder may have a lower frequency of agoraphobia than patients seen in anxiety disorder clinics. First, these cardiology patients with agoraphobia differ from those with the DSM-III diagnosis of agoraphobia with panic attacks because members of the latter group do not

310 B. D. BEITMAN ET ‘IL.

necessarily have current panic disorder. DSM-III requires that patients have had panic attacks some time in the past. Without current panic attacks members of this group would be less likely to be experiencing the often associated chest pain that could lead to cardiology consultation. Second, once persons develop agoraphobia, they are highly likely to per- ceive the disorder as psychologically based because their fears appear to be irrational. Therefore, they are more likely to seek psychiatric help. Agoraphobia may develop quickly after the onset of panics or take many years to develop. Evidence obtained by Thyer and Himle (1985) from a group of agoraphobics suggests that agoraphobic restrictions followed the onset of agoraphobia by an average of nine years. If this latter finding is substantiated, then our data suggest that people with panic disorder and without agoraphobia are far more likely to be found in cardiology settings than in psychiatric settings. However, in their sample of 32 agoraphobics with panic disorder, Uhde et al. (1985) reported that all subjects developed avoidance behaviors within six months (range three days to six months of their first panic attacks).

The small percentage of panic disorder subjects with agoraphobia is at variance with epidemiological studies of the general population. The prevalence rates for panic disorder (one month to one year) was 0.4- 1.21 100, while that of agoraphobia was 2.5000 to 5.81100 using DSM-III criteria (Weissman & Merikangas, 1986). These findings suggest that, for reasons yet to be determined, cardiology clinics attract patients who are less likely than the general population to develop agoraphobia.

As a result of the low prevalence rates in the study population, we have compared a group with a small number of subjects (1V = 8) to a larger group (N = 30) and run multiple statistical analyses. This method- ological weakness opens the possibility that the differences found could be the product of individual idiosyncracies. Future studies are necessary to substantiate these findings.

We conclude that patients with both current panic disorder and agoraphobia are more symptomatic than those with panic disorder alone when sampled from a cardiology population with atypical or nonanginal chest pain. These findings suggest the need for further understanding of the reasons some patients go on to develop agoraphobia and some patients do not.

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