The relationship of panic attacks to autonomically labile generalized anxiety

The Relationship of Panic Attacks to Autonomically Labile Generalized Anxiety Karl Koehler, Dimitrios Vartzopoulos, Some

data show

that probands

disorder (GAD) tend to manifest pure or nonpanicking autonomically might

be that

episodes system

suffering

from a mixed or panicking

more cross-sectional

form. This has generated

labile and stable subgroups patients

with

of GAD. The present on which DSM-III

mixed

GAD

findings,

and Hermann Ebel

somatic

the hypothesis

of generalized

anxiety

who have the

that mixed and pure GAD represent

anxiety

also have higher

form of generalized

anxiety than patients

disorder respectively.

lifetime

rates

derived using criteria disregarding

is based, failed to support this hypothesis,

A corollary

of autonomically

labile

the current exclusionary

though a trend in the expected

direction emerged. 0 1988

by Grune & Stratton,

Inc.

F

FREUD,’ most European psychiatrists’” regard panic attacks as OLLOWING an index of a unitary anxiety disorder’s severity. In contrast, many clinicians in North America support the view that the anxiety neurosis with panic attacks is a separate entity in its own right,435 a fact clearly reflected in DSM-III.6 Indeed, there is growing evidence for a few relevant discontinuities between panic disorder (PD) and generalized anxiety disorder (GAD), especially with respect to therapy’ and family loading.8 Some American researchers,’ however, doubt if GAD clearly represents an homogeneous anxiety disorder and suggest that the panic attack can usefully serve as a criterion to clinically subdivide the GAD category. Using this approach, Hoehn-Saric” found that “mixed” anxiety disorder defined in terms of panicking GAD patients, when compared with nonpanicking GAD probands, rated signiticantly higher on a Somatic Symptom Scale. In a replication of this study” in which the somatic subscale of the Hamilton Anxiety Scale” was also applied, panicking patients once again achieved higher scores on all somatic anxiety scales than did GAD probands without panic attacks. Hoehn-Saric” interpreted these findings in two ways. First, those with GAD might represent points on a continuum, their symptoms directly reflecting degree of severity. Alternatively, GAD probands might best be dichotomized into two distinct subgroups, each with a different constitutionality. One could be called the autonomically labile (AL) or autonomically hyperactive form of GAD associated with panic attacks. The second could be conceptualized as the more stable kind of GAD lacking autonomic hyperactivity; though various psychic phenomena as well as insomnia and somatic symptoms in conjunction with increased muscle tension are found in this form, panic attacks never occur. Taking this train of thought further, one might expect cases of GAD developing panic attacks at some point in time to present with more episodes of generalized anxiety manifesting higher degrees of somatic anxiety or autonomic lability during

From the University Psychiatric Clinic, Bonn. West Germatzy. Address reprint requests to Karl Koehler, M.D., University Strasse 25. 5300 Bonn I. West Germany. 0 1988 by Grune & Stratton, Inc. 0010-440X/88/2902-0002$03.00/0

Comprehensive

Psychiatry,

Vol. 29,

No. 2 (March/April),

1988:

Psychiatric

pp 9 1-97

Clinic. Sigmund-Freud-

91

92

KOEHLER, VARTZOPOULOS,

AND EBEL

the course of their illness than those with a nonpanicking form of GAD. The present paper’s primary purpose, then, is to test this hypothesis by determining the extent of autonomic lability in lifetime episodes of GAD found in a hospitalized, more or less “poor prognosis” segment from the entire universe of patients with either a panicking or a nonpanicking form of GAD. MATERIALS

AND METHODS

A search for the lifetime occurrence of clear-cut episodes of different kinds of anxiety disorder was carried out over 17 months by interviewing those consecutively admitted to an open ward for females in a University Psychiatric Hospital in West Germany, the overwhelming reason for admission being failure to respond to intensive outpatient drug therapy. Two hundred and fifty-five women with this kind of an unfavorable treatment response were admitted during the period under consideration and only these were included in the study. We felt these probands represented a proper starting point for deriving a suitably sized clinical group more or less equivalent to the “chronically anxious” sample (N = 33) recently drawn upon by Raskin et al.” in their attempt to validly separate the panic disorder and generalized anxiety subgroups possibly contained therein. In the present study general DSM-III6 criteria and guidelines were used, but some essential specific principles in diagnosing PD. agoraphobia, GAD, and depressive disorder were modified. On this basis, two groups were defined: the first consisted of probands who suffered at least one episode of GAD lifetime but never had an episode of panic disorder (= pure GAD), whereas the second comprised patients presenting not only with at least one episode of PD with or without avoidance behavior, but also with at least one episode of GAD during their course of illness (= mixed GAD). In the context of this diagnostic procedure, episodes fulfilling criteria for PD-even in the presence of moderate to severe avoidance behavior-were diagnosed as such and not as agoraphobia (AG) with panic attacks.14 Care was taken not to confuse the anticipatory anxiety that can occur between panic attacks as part of PD with the apprehensive expectation that can be found in GAD (criterion A3). Some data indicate that when this is done GAD tends to emerge as an independent anxiety disorder, but if not, it becomes a residual category.” For this reason we used the following operational dichotomy: criterion A3 of GAD was not rated positively when interval anxiety was directed toward the possibility of having the next panic attack, whereas anxiety aimed at other concrete aspects of everyday living meant criterion A3 of GAD had been fulfilled. In addition, since the number of symptoms from the remaining areas Al, A2, and A4 of GAD is not precise enough in DSM-III, the presence of at least eight of the remaining anxiety phenomena listed in these three areas was an additional requirement. As for the GAD duration criterion, this was left at 1 month since some evidence seems to indicate that more stringent chronological criteria may tend to confound rather than improve the descriptive validity of GAD.16 Furthermore, the relevant DSM-III diagnostic relationships between anxiety and depression were also disregarded so that the presence of affective disorder did not preclude the concomitant or sequential diagnosis of PD or GAD. This was done because many authors have suggested*,” that the research neglect of the nonnegligible comorbidity of anxiety and depressive disorder actually tends more to blur than clarify issues of validation. On the other hand, other forms of lifetime comorbidity were disregarded and all probands excluded if they had a DSM-III diagnosis of schizophrenic, other psychotic, paranoid, obsessive-compulsive, or somatization disorder at any point in time. Finally, any depression or anxiety found could not be due to an organic illness or connected with alcohol/substance dependence. Patients were given a semistructured interview based on a master list of all relevant DSM-III6 criteria. When a clinician had determined the first onset of panic and/or of generalized anxiety disorder, a careful search was made for further occurrences of these forms of anxiety on a year-by-year or other practical time segment by time segment basisdepending on the patient’s ability to remember-up to and including the index admission. Our focus, then, was not limited to an analysis of the cross-sectional presentation of these forms of anxiety disorder, as had been the case in those recent investigations”.” most relevant to the present one. Instead, our method was primarily geared towards longitudinally locating all panicking and nonpanicking GAD lifetime episodes and basically represented a modification of the detailed life-charting method for studying anxiety disorders proposed by Uhde et al.‘* Whenever a lifetime episode of GAD was found, its degree of somatic anxiety was determined using the somatic subscale of the Hamilton Anxiety Scale.” Since item 13 “behavior at interview” was superfluous in the context of a follow-back assessment of past GAD episodes, it was dropped. This meant that 24 was the highest possible somatic anxiety score that could be achieved on the basis of the six items

PANIC

A-ITACKS

AND

GENERALIZED

ANXIETY

93

focusing on somatic (muscular/sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, and autonomic symptomatology. A rating of at least 13 was required before an episode of GAD was considered to contain a clinically significant amount of somatic anxiety, in which case it was arbitrarily called AL; if the generalized anxiety episode failed to reach this cut-off point, it was referred to as autonomically stable (AS). The degree of Hamilton Scale-oriented psychic anxiety simultaneously present in the GAD episodes played no role in this process of classification. A cut-off of 13 for somatic anxiety was chosen because cross-sectional mean scores on the somatic subscale of the Hamilton Anxiety Scale for PD and GAD had been 13.2 and 8.7 respectively in that study in which Hoehn-Saric” hypothesized a dichotomy of GAD into autonomically labile and stable forms. Given our lifetime longitudinal focus, the requirement that an AL episode of GAD be defined in terms of a somatic anxiety score of at least 13 appears to be a rather stringent one. The statistical procedure employed in all comparisons involving categorical variables was Fisher’s exact probability test. An analysis of variance was applied for continuous variables.

RESULTS

Twelve percent (n = 30) of the 255 hospitalized women interviewed proved to be suitable for the present investigation. Of these 57% (n = 17) fulfilled the modified DSM-III1 criteria for both PD and GAD occurring separately or concomitantly lifetime (= mixed GAD); the remaining 43% (n = 13) suffered only from episodes of GAD during the course of their illness (= pure GAD). Age at index admission in probands with pure GAD (38.4 it 11.2 years) and mixed GAD (41.3 -c 16.1 years) did not differ significantly. The same was true for age at first onset of psychiatric illness ever with respect to either an initial appearance of AG, PD, GAD, specific forms of depressive disorder, or any combination thereof (28.5 * 7.6 v 30.4 * 8.8 years for pure GAD and mixed GAD respectively). Duration of illness was also not significantly different in the two groups (9.8 k 7.0 years for pure GAD and 10.9 _t 8.9 years for mixed GAD). Table 1 lists the lifetime episode rates for AL and AS episodes of GAD in pure and mixed forms of GAD. Although there was a tendency for the pure GAD group to have more GAD episodes of any kind per proband, the difference was not significant. As might have been predicted, mixed GAD had more AL episodes of GAD per proband whereas there were more AS episodes of GAD per proband in pure GAD; in both instances differences were nonsignificant. Lifetime rates for different combinations of AL and AS episodes of GAD in pure GAD and mixed GAD are given in Table 2. These figures show that mixed GAD, as might have been expected, contained more probands presenting only with AS episodes of GAD (41% v 3 1%); this group also had more probands with at least one AL and at least one AS episode of GAD lifetime (24% v 8%). Moreover, again in keeping with the hypothesis, the pure GAD group had more probands with only AS Table

1.

Lifetime

Rates

for AL and AS Episodes

of Generalized

with Pure or Mixed Forms of GAD.

GAD Episodes/Proband* AL-GAD Episodes/Probandt AS-GAD Episodes/Proband$ *One-way tone-way *One-way

ANOVA: ANOVA: ANOVA:

F( 1,28) F( 1,28) F( 1.28)

Anxiety

in Probands

Pure GAD (N = 13)

Mixed GAD

1.9 + 1.2 0.9 + 1.4 1 .o f 0.9

1.8 * 1.4 1.0 + 1.3 0.8 lr 1.0

= 0.04, not significant. = 0.03, not significant. = 0.2 1, not significant.

(N = 17)

KOEHLER, VARTZOPDULDS,

94

Table 2. Lifetime

AND EBEL

Rates for Combinations of AL and AS Episodes of Generalized in Probands with Pure or Mixed Forms of GAD.

Anxiety

Pure GAD N= 13 (%I

Mixed GAD N= 17 (%I

4 (31) 6 (61) 1 03)

J (41) 6 (35) 4 (24)

Only AL-GAD episodes* Only AS-GAD episodest AL-GAD + AS-GAD episodes3

*Fisher’s exact probability test: P = 0.25, not significant. tfisher’s exact probability test: P = 0.10, not significant. *Fisher’s exact probability test: P = 0.2 1, not significant.

episodes of GAD nonsignificant.

(61% v 35%).

Differences

in all comparisons,

however,

were

DISCUSSION The overwhelming majority of cases of PD-up to 80% in one recent major report”-seem to manifest GAD concomitantly or separately during the course of illness. This certainly is an important reason for asking how PD clinically differs from GAD. Recent studies’0~1’~20~22 show that patients with panic attacks clearly present with more somatic symptoms than those with generalized anxiety states. Gelder,23 however, rightly points out that symptom differences of this kind fail to validly separate these conditions since the reported rates are merely a function of the panic attack’s definition. For this reason, the question as to whether any distinctions at the symptom level exist between PD and GAD might usefully be rephrased to read: Are there any symptom differences between these two anxiety disorders not directly due to or a reflection of the panic attacks? In order to provide a partial provisional answer to this question, we deliberately focused on determining the extent of somatic features linked with each episode of GAD lifetime in probands with PD at some point (= mixed GAD) and in GAD patients who never had an episode of panic disorder at any time (= pure GAD). As it turned out, the probands comprising the pure GAD subgroup in the present sample in reality represented a “super-pure” variety in the sense that they not only never suffered from a diagnosable episode of PD lifetime, but also never experienced a single panic attack. Our aim, then, was to determine if there would be a sizeable amount of somatic anxiety (= rating positive for autonomic lability) in more lifetime episodes of GAD in those who panicked than in those who did not. The present findings failed to support this hypothesis, though a trend in the expected direction emerged. Thus, mixed GAD tended to have the higher rate of AL episodes of GAD per proband during the entire course of illness and pure GAD more AS episodes of GAD per proband (Table 1). Moreover, pure GAD had a greater number of patients with only AS episodes of GAD whereas mixed GAD presented with more cases manifesting only AL episodes of GAD lifetime; furthermore, more probands with mixed GAD had both AL and AS episodes of GAD (Table 2). These findings, however, must be interpreted with caution because of the methods implemented. Thus, of the legitimate objections that might be raised in this context, three seem central, One consideration might be that our samples were not truly representative. Angst

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and Dobler-Mikola,24 for example, make a case for beginning with representative samples of various anxiety states in the general population and not with what they call a few unrepresentative, although perhaps very typical clinical presentations. With typical they seem to mean ideally typical in the sense of clear-cut “pure” cross-sectional cases without any diagnostic overlapping or comorbidity. Our samples were certainly not typical in this sense since we deliberately disregarded some central DSM-III hierarchical rules for diagnosis. However, we believe our longitudinal diagnostic perspective as well as choice of inpatients was justified, allowing as it did to detect and focus on a particularly important subgroup representative of women with longstanding intermittent or chronic psychiatric problems and with a history of doing poorly on outpatient drug therapy. Indeed, the fact that the overwhelming majority of our probands presented with considerable depressive disorder comorbidity to some extent appears to support this contention; of the total number of GAD patients comprising both our mixed and pure groups, 77% suffered from a DSM-III specific depressive disorder at some time during the course of illness.25 Another objection might refer to the clinical definitions used for the category of mixed GAD and is probably a criticism easily applicable to other modern investigations attempting to separate PD from GAD. Research definitions of PD in these studies usually were couched in such a way that evidence tending to support the distinction often enough remained confounded because agoraphobics had been included in those samples primarily defined in terms of panic attacks. Indeed, in most investigations based on DSM-III guidelines, rates for the coupling of AG with PD tended to be quite high, namely, between 42% and 97%;‘9*26-30 obviously, any observed differences between a group with panic attacks or PD, on the one hand, and GAD, on the other, may actually represent differences better interpreted in terms of separating AG and GAD. In the present study, 42% of panicking GAD patients but only 15% of nonpanicking GAD probands fulfilled DSM-III criteria for AG at some time so that this interpretation of our results based on comparing mixed GAD and pure GAD may also be valid. A third important objection to our findings can be levelled against the definition of somatic anxiety favored, one apparently a part of Hoehn-Saric’s” concept. Tyrer,3’,32 for example, criticized defining somatic anxiety solely in terms of the somatic anxiety score derived from the Hamilton Anxiety Scale.‘* Instead, he supports a notion of anxiety conceptualized in terms of personal cognition: anxious patients can only be relegated to a somatic or somatosthenic anxiety category when they interpret their bodily symptoms as being at the center of their anxious concerns. Tyrer makes the important point that not all patients with this form of anxiety actually present with marked somatic symptomatology or high levels of physiological arousal. In practice, however, his cognition-oriented concept of somatic anxiety seems to limit its applicability to cross-sectional psychopathology for he emphasizes the “impossibility” of using retrospective ratings to detect it.19 That is one reason why we opted for not following this approach. Given our method of trying to detect all past episodes of generalized anxiety disorder-which already implied a search for the somatic symptomatology as defined by DSM-III6 contained therein-we could just as well have implemented two of its four defining symptom clusters, namely, muscle tension and autonomic hyperactivity, to serve as the basis of a scoring system for somatic anxiety; recently,

96

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AND EBEL

Barlow et al.” did something similar, deriving a severity of symptoms score (highest possible = 16) by rating all four GAD symptom clusters. In the present context, however, it seemed more appropriate to use the Hamilton ScaleI since this allowed for drawing upon an empirically plausible cut-off for somatic anxiety referable to Hoehn-Saric’s” data. It seems certain that we missed some or even most separate occurrences of life-time episodes of GAD because patients probably remembered only severe instances of anxiety lasting at least a month but failed to recall milder and/or shorter episodes. On the other hand, some panicking GAD probands, after having experienced the dramatic nature of a panic attack for the first time, might have tended to direct much more attention to the somatic features of any associated generalized anxiety they suffered from at other times, thereby better remembering the GAD episodes. We also might have missed detecting lability in those past episodes of GAD we actually found because the cut-off of 13 was much too high for rating retrospectively. It must be left to a prospective study, then, perhaps one using Tyrer’s concept of somatosthenic anxiety, to determine the “true” extent of autonomic lability in lifetime episodes not only for various “poor prognosis” segments but especially for the entire universe of panicking and nonpanicking forms of GAD. REFERENCES 1. Freud S: The justification of detaching from neurasthenia a particular syndrome: The anxietyneurosis. Neurologisches Zentralblatt, 2. Reprinted (1940) in Collected Papers, 1 (trans J Riviere), 1895, pp 76-106 2. Angst J: Features and diagnosis of anxiety, in Lader MH, Davies HC (eds): Drug Treatment of Neurotic Disorders. London, Churchill Livingstone, 1986, pp 70-75 3. Marks IM: Diagnosis of panic states: A European view, in Lader MH, Davies HC (eds): Drug Treatment in Neurotic Disorders. London, Churchill Livingstone, 1986, pp 160-165 4. Klein DF: Anxiety reconceptualized, in Klein DF, Rabkin J (eds): Anxiety: New Research and Changing Concepts. New York, Raven, 1981, pp 235-263 5. Klerman GL: Diagnosis of panic states: A North American view, in Lader MH, Davies HC (eds): Drug Treatment of Neurotic Disorders. London, Churchill Livingstone, 1986, pp 251-258 6. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. Third edition. Washington DC, American Psychiatric Association, 1980 7. Barlow DH, Cohen AS, Waddell MT, et al: Panic and generalized anxiety disorders: Nature and treatment. Behav Ther 15:431-449, 1984 8. Crowe RR: The genetics of panic disorder and agoraphobia. Psychiatr Dev 2:17 l-l 86, 1985 9. Hoehn-Saric R, McLeod DR: Generalized anxiety disorder. Psychiatr Clin North Am 8:73-88, 1985 10. Hoehn-Saric R: Characteristics of chronic anxiety patients, in Klein DF, Rabkin J (eds): Anxiety: New Research and Changing Concepts. New York, Raven, 198 1, pp 399-409 11. Hoehn-Saric R: Comparison of generalized anxiety disorder with panic disorder patients. Psychopharmacol Bull 18:104-108, 1982 12. Hamilton M: The assessment of anxiety states by rating scales. Br J Med Psycho1 32:50-55, 1959 13. Raskin M, Peske HVS, Dickman W, et al: Panic and generalized disorders. Developmental antecedents and precipitants. Arch Gen Psychiatry 39:687-689, 1982 14. Koehler K, Vartzopoulos D, Ebel H: Agoraphobia and depression: Relationships and severity in hospitalized women. Compr Psychiatry 27:533-539, 1986 15. Barlow DH, Blanchard EB, Vermilyea JA, et al: Generalized anxiety and generalized anxiety disorder: Description and reconceptualization. Am J Psychiatry 143:40-44, 1986 16. Breslau N, Davis GC: DSM-III generalized anxiety disorder: An empirical investigation of more stringent criteria. Psychiatry Res 14:231-238, 1985

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