The development of agoraphobia in panic disorder: a predictable process?

Journal of Affective Disorders 58 (2000) 43–50 www.elsevier.com / locate / jad

Research report

The development of agoraphobia in panic disorder: a predictable process? ¨ Gernot Langs a , *, Franz Quehenberger b , Karin Fabisch a , Gunter Klug a , Hans Fabisch a , Hans Georg Zapotoczky b

a ¨ ¨ Psychiatrie, Graz, Germany Universitatsklinik f ur ¨ Medizinische Statistik und Informatik, Graz, Germany Institut f ur

Received 31 October 1998; received in revised form 1 March 1999; accepted 3 June 1999

Abstract Background: Panic attacks are conceptualized to be the central feature of both panic disorder without (PDU) and with agoraphobia (PDA). As a sizeable percentage of panic patients do not develop avoidance behavior, other factors than ‘panic attacks’, in general, must influence the different courses of the disorder. Method: We studied 84 outpatients suffering from PDU or PDA concerning different factors which were hypothesized to influence the development of agoraphobia. Results: ‘Earlier age of onset’, ‘fear of losing control’ and ‘chills or hot flushes’ turned out to correlate statistically significantly with PDA, while ‘chest pain or discomfort’ occurred more often in PDU. Limitations: The present study used retrospective data. Conclusions: The results of this study suggest that the development of agoraphobia in panic disorder is influenced by specific variables and is not a purely coincidental process.  2000 Elsevier Science B.V. All rights reserved. Keywords: Agoraphobia; Panic attacks; PDU

1. Introduction Panic attacks and the development of agoraphobia appear to have a clear linkage, a concept which is shared by current biological and psychological models on panic disorder and agoraphobia (Margraf et al., 1986; Telch et al., 1989). This ‘American view’ is also illustrated in DSM-III-R and DSM-IV, whereas the ‘European view’ (ICD 10) makes a clear *Corresponding author.

distinction between ‘panic disorder’ and ‘agoraphobia with panic attacks’, thus favoring the different clinical presentations of these disorders and less the common central feature of anxiety attacks. While the term ‘agoraphobia’ literally has the meaning of ‘fear of public places’, agoraphobic avoidance behavior in panic disorder is now understood as a coping strategy in order to diminish the risk of experiencing anxiety attacks in feared situations. The cognitive model states that panic attacks are caused by the individuals’ tendency to interpret

0165-0327 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 99 )00097-X

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G. Langs et al. / Journal of Affective Disorders 58 (2000) 43 – 50

bodily sensations in a catastrophic fashion. These unpleasant sensations are perceived as an indication for an immediately impending physical or mental disaster. The catastrophic cognitions evoke an increase in apprehension, which produces a further increase in bodily sensations until it culminates in a vicious circle in a panic attack (Clark, 1986). Because anticipated fear as well as internal stimuli may trigger the emergence of unpleasant bodily sensations and the exaggerated appraisal of the negative consequences of anxiety attacks, individuals start to restrict their activities outside their ‘safe’ environment and avoid ‘public places’. However, it has not been clarified yet why some individuals suffering from panic disorder exhibit agoraphobic avoidance while others do not. Epidemiologic studies have shown that 13–16% of the general population experience at least one panic attack during their life time, but only a small percentage develop panic disorder with agoraphobia (Wittchen and Essau, 1991). Evidently there must be other factors than just the existence of panic attacks in general, which either predispose, or, on the other hand, protect individuals from developing avoidance behavior. Several hypotheses have been tested in order to find the reasons for the different courses of the illnesses, but results have been diverging. While the ‘severity hypothesis’ (Craske and Barlow, 1988; Mavissakalian, 1988) and the influence of ‘duration of illness’ seem to have no predictive value (Rapee, 1988; Starcevic et al., 1993a,b), relevant data have emerged for the role of cognitive factors (Rapee, 1988; Telch et al., 1989; Zoellner et al., 1996). Different symptom structures of anxiety attacks and anticipation (either of experiencing panic attacks or of their consequences) may also play a key role in the development and maintainance of agoraphobia (Starcevic et al., 1993b; Pio-Abreu et al., 1998; Segui et al., 1998). Furthermore ‘age of onset’ has emerged to be a risk factor for avoidance behavior, as panic disorder patients with early onset (i.e. before the age of 25) more often exhibit phobic symptoms than those with late onset (Wittchen and Perkonigg, 1993). The aim of this study was to answer the following questions: 1. Is there an influence of cognitive factors (catas-

trophic thinking) on the development of agoraphobia? 2. Do ‘age of onset’ and ‘duration of illness’ cause different courses of the disorder? 3. Is there a difference in symptom profiles between patients with uncomplicated panic disorder (PDU) and panic disorder with agoraphobia (PDA)?

2. Methods

2.1. Subjects and procedure The sample comprised 84 patients, 26 suffering from PDU and 58 from PDA according to DSM-IIIR criteria. The subjects were participants of a study on the role and influence of personality disorders in panic patients with or without comorbid (lifetime) major depression. Inclusion criteria were panic disorder with or without agoraphobia. Exclusion criteria were affective disorders other than major depression, organic mental disorders, schizophrenia or other psychotic disorders, current substance related disorders and eating disorders. For categorical diagnosis SCID-I for DSM-III-R was used. Symptom profiles were obtained from the panic disorder section of the SCID. Patients were asked to recall the symptoms of their first spontaneous panic attack. As not all patients were able to do so, the original sample of 98 had to be reduced to 84 subjects. Details on mode of recruitment, diagnostic procedures and interrater reliabilty have been published elsewhere (Langs et al., 1998). All patients signed informed consent before entering the study.

2.2. Statistical analysis In order to investigate the association of agorapobia within panic patients with various traits, logistic regression was used. The influence of categorical traits is given as odds ratios (OR) relative to a reference category, 95% confidence intervals (CI) were calculated according to Gardner and Altman (1989). For continuous traits it was assumed that a constant odds ratio arises if the value is raised one unit. P-values and confidence intervals rely on the Wald test (Kleinbaum et al., 1982). In order to get

G. Langs et al. / Journal of Affective Disorders 58 (2000) 43 – 50

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3.2. Age of onset and duration of illness

those risk factors which contribute most and to rule out those which make no contribution independent from the others, backward variable selection was performed on a subset of traits. Only variables reaching p , 0.05 were kept in the calculation. The performance of the logistic regression was assessed by the percentage of correctly classified patients with PDU or PDA. A predicted probability of greater than 0.5 was classified as agoraphobia. In addition Wilcoxon tests were performed for continuous traits. P-values were rounded off to 2 decimal places or at least to one significant digit. All statistical tests were performed at the 5% error level.

Age of onset (AOP) for panic disorder was 27.93 yrs. (SD 5 8.44) in the agoraphobic group and 34.25 yrs. (SD 5 9.72) in the non agoraphobic group ( p 5 0.003, Wilcoxon test). Duration of illness at time of recruitment had a median of 11 months for the PDU and 27 months for the PDA groups ( p 5 0.02, Wilcoxon test). A separate calculation for AOP < 25 (Table 1) shows that the OR for acquiring agoraphobia is 4.17 for subjects with an early onset of the disorder.

3.3. Symptom profiles Fig. 1 illustrates the symptom profiles of the subjects with and without agoraphobia; three of the 13 items (X, XI and XIII) reach significant p-values.

3. Results

3.1. Sociodemographic variables 3.4. Univariate analysis and backward selection Table 1 summarizes sociodemographic data of the two groups, none of them showing significant differences. Subjects did not differ significantly in age at the time of recruitment (PDU: 38.19 years, SD 5 10.32; PDA: 33.48 years, SD 5 9.48; p 5 0.08).

For items and continuous risk factors with p , 0.05, a univariate analysis was performed. The OR for duration of illness ( p 5 0.02) and AOP ( p 5 0.005) were 2.54 (95% CI 5 1.11–5.53, x 2 5 5.46)

Table 1 Agoraphobia, risk factors and odds ratios PDU (%)

PDA (%)

OR

95% CI

p

Female Male

61.5 38.5

58.6 41.4

1.13

0.44–2.91

0.8

9 yrs. of school 12 yrs. of school Some college University graduate

11.5 73.1 11.5 3.8

8.6 77.6 5.2 8.6

1.42 0.6 3.0

0.31–6.55 0.07–5.14 0.23–39.61

0.65 0.64 0.4

Employed Unemployed Housewife University student Retired

76.9 3.9 7.7 7.7 3.8

65.5 12.1 5.2 15.5 1.7

3.68 0.79 2.37 0.53

0.42–32.08 0.12–5.12 0.47–12.03 0.03–8.87

0.24 0.8 0.3 0.66

Single Married Divorced

38.5 57.7 3.8

36.2 53.4 10.3

0.98 2.86

0.37–2.6 0.3–27.03

0.97 0.36

No Yes

84.6 15.4

56.9 43.1

4.17

1.27–13.63

0.02

Sex

Educational level p , 0.62

Occupational level p , 0.57

Marital status p , 0.69

AOP < 25 yrs

G. Langs et al. / Journal of Affective Disorders 58 (2000) 43 – 50

46

Fig. 1.

I

II

III

IV V VI VII VIII IX X XI XII XIII

Item

OR (95% CI)

x2

df

p-Value

Sensations of shortness of breath Feeling dizzy, unsteady, lightheaded, or faint Palpitations, pounding heart, or accelerated heart rate Trembling or shaking Sweating Feeling of choking Nausea or abdominal stress Derealization or depersonalization Paresthesias Chills or hot flushes Chest pain or discomfort Fear of dying Fear of going crazy or losing control

0.53 (0.18–1.52)

1.40

1

0.24

2.54 (0.88– 7.31)

2.99

1

0.08

0.99 (0.28–3.56)

0.0002

1

0.99

1.51 (0.57–3.98)

0.69

1

0.41

0.72 (0.28–1.84) 0.82 (0.32–2.09) 1.80 (0.71–4.59)

0.48 0.17 1.52

1 1 1

0.49 0.68 0.22

0.72 (0.28–1.85)

0.47

1

0.49

1.02 (0.39–2.65) 2.97 (1.11–7.97)

0.002 4.66

1 1

0.96 0.03

0.34 (0.12–0.98)

3.97

1

0.05

0.49 (0.17–1.41) 3.96 (1.47–10.67)

1.75 7.43

1 1

0.19 0.01

G. Langs et al. / Journal of Affective Disorders 58 (2000) 43 – 50 Table 2 AOP, corrected for duration of illness

Duration of illness AOP

47

Table 4 Classification table for agoraphobia

OR (95% CI)

x2

df

p-value

Predicted

2.01 (0.88–4.48) 0.93 (0.88–0.99)

2.70 5.27

1 1

0.1 0.02

no

yes

15 7

11 51 Overall:

and 0.92 (95% Cl 5 0.87–0.98, x 2 5 7.77), respectively. The OR (0.34) for item XI indicates that the existence of ‘chest pain or discomfort’ protects individuals from developing agoraphobia. When AOP was corrected for ‘duration of illness’, this factor no longer reached significance (Table 2, Fig. 2). Table 3 lists the results of the backward variable selection. The OR for AOP reveals that the odds of developing avoidance behavior diminishes with this factor each year. Independently, the existence of

Observed No Yes

% Correct

57.69 87.93 78.57

items X and / or XIII supports agoraphobia, while item XI still keeps its ‘protective value’ in this model. The logistic regression model with a predicted probability of 0.5 as cut value predicts 87.9% of cases with agoraphobia and 57.7% of cases without agoraphobia correctly, with an overall probability of 78.6%. (Table 4). The overall OR predicting diagnostic group membership is 9.9.

4. Discussion

Fig. 2. Plot of age at onset of panic against duration of illness of anxiety. The additional factor of development of agoraphobia defines 2 patient groups. Inspection of the plots does not suggest that there is a correlation of age at onset and duration of illness within groups. Agoraphobia is more prevalent within patients with an age of onset < 25 years.

Table 3 Results of backward variable selection Variable

OR (95% Cl)

x2

df

p-value

AOP X XI XIII

0.91 (0.85–0.97) 3.49 (1.09–11.13) 0.26 (0.07–0.98) 3.48 (1.13–10.71)

8.64 4.42 3.91 4.67

1 1 1 1

0.003 0.04 0.05 0.03

One of the major findings of this study is that the development of agoraphobia in panic disorder is not a straightforward process, but influenced by different factors. These include age of onset, the presence of a specific cognition (fear of going crazy) and the experience of ‘chills or hot flushes’ during panic attacks. On the other hand, the presence of ‘chest pain or discomfort’ reveals to have a ‘protective effect’, thus decreasing the risk of avoidance behavior. Age of onset has emerged to effect the development of agoraphobia in the majority of earlier studies, both from epidemiological and clinical research (Noyes et al., 1987; Buller et al., 1991; Wittchen and Perkonigg, 1993; Starcevic et al., 1993a), but not in all (Thyer et al., 1985; Scheibe and Albus, 1992). The conflicting results may be due to the mode of recruitment, the use of different interviews (SCID, CIDI) and the application of different diagnostic criteria (DSM-III, DSM-III-R). However, Wittchen and Perkonigg (1993) conclude that different pathological mechanisms or help-seeking behaviors may cause the different courses of the disorder. Our finding that the probability of acquiring agoraphobia decreases with each year of later onset of panic disorder is also supported by earlier studies,

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which showed that the prevalence of agoraphobia is significantly lower in later life (Krasucki et al., 1998). According to research data by Marks and ¨ Gelder (1966) and Ost (1987), specific phobias usually have their onset in childhood, social phobia during adolescence and agoraphobia in young adulthood. Therefore one may draw the conclusion that ‘age of onset’ constitutes both a vulnerability and protective factor in the development of phobias: if panic disorder first starts during the most ‘vulnerable’ phase in young adulthood, the risk of acquiring agoraphobia is increased compared to later onset. Furthermore, the results of this study are in accordance with research data on the influence of familial liability on panic disorder, which allow us to come to the conclusion that earlier age of onset of panic disorder with agoraphobia reflects genetic penetrance and increased vulnerability (Goldstein et al., 1997; Battaglia et al., 1998). Another finding of the present study, namely that duration of illness does not influence the course, is in agreement with previous studies (Uhde et al., 1984; Rapee, 1988; Starcevic et al., 1993a,b). Garvey and Turkson (1984) even report, that agoraphobic avoidance usually begins within the first six months after the first panic attack. A further question concerned the symptom profiles of the panic attacks of the two groups. Even though most of the earlier studies have shown that these differ concerning the somatic aspect, results concerning cognitive aspects have been diverging. This may be due to the fact, that some authors used questionnaires which did not make a clear distinction between ‘fear of dying’ and ‘fear of going crazy’ (Noyes et al., 1987; Wittchen and Perkonigg, 1993). Our results reveal that it is the specific fear of ‘loss of control or going crazy’ which supports avoidance behavior. This is in accordance with earlier studies, which, in addition, also found that this cognition is highly correlated with ‘chills or hot flushes’, as these two items load together in a principal component analysis of panic symptoms (Telch et al., 1989; Starcevic et al., 1993b; Pio-Abreu et al., 1998; Segui et al., 1998). Furthermore it has been shown that fearful cognitions about social and mental consequences are stable in between panic attacks (Zoellner et al., 1996) and, in addition, Amering et al. (1997) revealed that embarrassment about the first panic attack predicts agoraphobia in panic patients. Our

finding that ‘chest pain or discomfort’ (item XI) is more prevalent in PDU is in accordance with earlier research reports, which also showed that PDU was more often correlated with this item than PDA (Noyes et al., 1987). If ‘chest pain’ is a prominent and persistent symptom it may even justify the comorbid diagnosis of a ‘somatoform (pain) disorder’ for these patients (Ladwig et al., 1998; Mayou, 1998) and require appropriate therapeutic strategies. Overall these results suggest that the development of agoraphobia is influenced by the fear of social consequences (‘‘If I go crazy, people will think I am a lunatic and will send me to a psychiatric hospital’’) and embarrassment (‘‘They won’t talk to me anymore’’) and not by hypochondrical fears in general. There are several limitations to the study. First of all, this concerns the mode of recruitment, as the subjects were patients of a tertiary care center. Still, the significance of different symptom profiles and of ‘age of onset’ for the development of agoraphobia have also been shown for an epidemiological sample. Secondly, like all previous studies on ‘onset’, the present one was necessarily retrospective too. As symptom profiles have been recalled by the patients, these might look different if they had been made by continuous monitoring as suggested by de Beurs et al. (1994). Still, this procedure was not possible for our study as patients were asked about the symptoms of their first attack. However, it has to be noted that all patients whose data were taken into calculation could vividly recall their first panic attack. The finding that a great majority of patients are able to do so was first described by Lelliot et al. (1989) and confirmed in later studies (Amering et al., 1997; O’Rourke et al., 1996). The symptom checklist of the panic disorder section of the SCID was chosen for two reasons: (1) the SCID is an instrument recommended for panic disorder research (Shear and Maser, 1994), and (2) the interview was considered to have an advantage over a questionnaire because it was possible to give detailed instructions to the subjects before the items of the section were endorsed.

5. Conclusions The results of this study suggest that the development of agoraphobic avoidance in panic patients is

G. Langs et al. / Journal of Affective Disorders 58 (2000) 43 – 50

independently influenced by distinct factors and is not purely coincidental. Even though our model is capable of classifying 78.57% of our patients correctly, further research is warranted to which other variables may contribute to predict agoraphobia. These might include different help seeking behaviors in patients with earlier onset and the possibility of an increased ‘phobia proneness’ in patients who experience their first panic attack in young adulthood. We also suggest that further research on the efficacy of therapeutic strategies should take our findings into consideration. The use of either antidepressant medication or cognitive behavioral methods has proved to be useful in the treatment of PDU and PDA for many patients, but a considerable number shows an incomplete response (APA Guidelines, 1998). In these patients, a combination of both antipanic medication and cognitive behaviour therapy may be useful, but no parameters which patients might benefit from a combined treatment have been identified yet. It has been suggested, that patients with severe agoraphobia may profit from this combination, but further research should also focus on ‘early onset’. Within the cognitive approach therapists should clearly differentiate if the hypochondrial fears primarily concern somatic or mental aspects, as these seem to evoke different courses of the disorder. The use of distinct strategies may prove useful, as panic patients with somatic hypochondrial fears also exhibit typical checking behaviors and reassurance seeking, which ask for specific behavioral techniques. In summary our results indicate that panic disorder need not take an inevitable course leading to disabling avoidance behavior. An early recognition of risk factors may allow the use of specific treatment strategies, which may enhance the chances of early and full remission.

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