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Panic disorder: Residual symptoms after the acute attacks abate
Panic Disorder: Residual Symptoms Acute Attacks Abate
After the
Wayne Katon, Peter P. Vitaliano, Kathleen Anderson, Michael Jones, and Joan Russo Patients attacks
with
a past history
were compared
panic attacks
had significantly
as significantly suffered
more
anxiety
needs to be focused of the relationship
and avoidance
Like patients
with
symptoms
on the longitudinal
disorder
the controls
with
episodes
anxiety
with past
tests, as well
who
had never
of superimposed
who recover from panic disorder,
depression,
and phobias.
course of panic disorder in order to enhance
among the anxiety disorders (generalized
by Grune & Stratton,
than
acute
Patients
scores on psychological
of patients
of anxiety,
from
anxiety attacks.
behavior,
dysthymic
to be a subgroup
residual
panic disorder) as well as major affective B 1987
no longer suffering
higher anxiety and depression
there appears
significant
who were
who had never experienced
social phobias
attacks.
major depression, are left with
of panic disorder
to patients
More
but
research
understanding
anxiety, social phobia, agoraphobic,
and
disorder.
Inc.
I
YEARS, Keller and colleagues have developed the concept of N RECENT as the superimposition of acute depressive episodes on “double depression” chronic depressive disorder.’ Akiskal et al.’ have also noted that dysthymic disorder is often complicated by superimposed major depressive episodes. Although anxiety disorders are also quite common in the general population, few epidemiological studies have studied the longitudinal course of anxiety disorders such as panic disorder. Panic disorder tends to be a relapsing, remitting disorder. Studies that have reevaluated patients with panic disorder up to 20 years after initial diagnosis found that 50% had some level of disability and 73%) to 93% were symptomatic.‘-” Patients with panic disorder are also at high risk for the development of major depression, agoraphobia, and generalized anxiety.‘,’ The separation of anxiety from depression is particularly difficult with frequent “crossing over” from one diagnosis to the other.‘k9 Anxiety states frequently change to depressive illness, depression is a common complication of agoraphobia and panic disorder and generalized anxiety often increases in the course of panic disorder.7,8.‘0 Although studies have documented that many patients who develop major depression have had longterm problems with dysthymic disorder and that, if left untreated, they often continue to have chronic depressive symptoms, less is known about the longterm course of panic disorder.‘.2 Once there has been a remission of the acute panic attacks, do the patients’ symptoms of anxiety and depression cease, or as in depression, do patients have chronic anxiety and depressive symptoms that are subclinical, but apt to exacerbate during stressful life events? Tyrer has suggested that although patients with panic disorder may have complete resolution of the acute anxiety in the short term, both anxiety and minor depression usually persist.’ In fact, Tyrer’ has coined the term “the general neurotic syndrome” to From the Division of Consultation and Liaison Psychiaq. University of Washington Medical School, Seattle. Address reprint requests io Wayne Katon, M.D., Associate Professor, lJniversit_v of Washington Medical School, Psychiatry and Behavioral Sciences RP-I 0, Seattle. WA 98195. 0 I987 by Grune & Stratton, Inc. 0010-440X/87/2802-0006$03.00/0 Comprehensive
Psychiaby,
Vol. 28,
No. 2 (March/April),
1987:
pp 15 1- 158
151
152
KATON
ET AL
classify patients who pass “chameleon-like through different diagnostic hues depending on the nature of the stressors they encounter.” Tyrer emphasized the changeable nature of this syndrome, noting that patients have agoraphobia, social phobias, panic disorder, generalized anxiety, and hypochondriasis during their life course. Sometimes only one or two illnesses are present, sometimes all. The purpose of this study was to examine the present symptomatology of patients with a history of past panic disorder as compared to patients who have never suffered from anxiety attacks. The central hypothesis tested was that patients who suffered from panic disorder in the past but who had not had a panic attack for at least 3 months would have higher scores than controls on psychological tests of anxiety, depression, and somatization as well as having significantly more social phobias and avoidance behavior. METHOD Subjects were selected from the University
of Washington
Family Medical Center (Seattle)
a primary
care facility which, similar to other primary care practices, routinely sees a high percentage of anxiety/depression cases. The Family Medical Center is an outpatient clinic with 7,000 registered patients and 19,000 outpatient visits annually. It is staffed by 30 residents and faculty physicians. The ratio of female to male visits is 2.5 to one. In this university family medical practice, 195 randomly selected primary care patients 17 years of age and over, who were coming in to the primary care physician for a routine symptomatic visit” were given a modified form of the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule (DE)‘* by two trained interviewers (KA was a senior psychiatry resident, MJ was a medical student). Prior to the study, both interviewers were trained in the use of the DIS by the senior author (WK), who has utilized the DIS in multiple past studies and received training from the University of Washington psychiatrists who were taught the interview in St Louis. Training in the use of the interview included direct observation of the experienced interviewer, direct supervision of the research interviews, and interrater trials. In addition, 10% of the interviews were completed and independently scored by both interviewers and they were in almost complete agreement in the classification of panic disorder (Kappa = .90, P < ,006). Patients who had a history of panic attacks with at least four somatic symptoms were interviewed further in order to screen for alcohol abuse/ dependence and major depression. One out of every four patients who did not meet criteria for panic disorder was screened for major depression and alcohol abuse; the other three out of four were not further screened by interviewers. Patients were classified as having panic disorder, major depression, and/or alcohol abuse utilizing Diagnostic and Statistical Manual of Mental Disorders (ed 3) (DSM-III) criteria.” The cutoff point in DSM-III criteria for panic disorder requires that patients must have three panic attacks in a 3-week period and at least four autonomic symptoms occurring during an attack. An additional diagnosis was added (and termed simple panic) for patients who fulfilled the criteria of acute anxiety attacks that included four or more autonomic symptoms, but who had less than three attacks in a 3-week period. Patients who suffered from panic disorder or simple panic, but who had not had symptoms for 3 or more months were labeled as having past panic disorder or past simple panic.
Subjects The 195 patients (53 male and 142 female) ranged in age from 17 to 84 years with a mean of 37.2 and a median of 33.6 years. Ninety-six patients were married, 67 were never married, and 3 1 were separated, divorced, or widowed. There were 176 Caucasian, 11 black, four Hispanic, and four Asian patients. In terms of Hollingshead social class index, 1.7% of patients were from social class I, 14.4% were from social class II, 46% were from social class III, 23.6% were from social class IV, and 14.4% were from social class V. Of the patients approached for the study, 53% consented to be interviewed. Compared with the norms of the clinic population, there were no significant differences in age, ratio of female-to-male patients’ visits to the clinic, race, or socioeconomic status.
Measures
and Statistical
Analyses
In order to help validate the diagnostic findings, patients were asked to complete a battery of psychological tests including the Beck Depression Inventory (short form),14 Zung Anxiety Scale (SAS),”
RESIDUAL
SYMPTOMS
and the SCL-90
OF PANIC
153
DISORDER
subscales on Depression,
Anxiety,
Phobic-Anxiety,
Somatization.
and Additional
Items.”
Major analyses compared primary care patients with and without panic disorder. Comparisons were made on demographic variables; presence of coexisting diagnoses of depression or alcoholism; help seeking behavior; number of phobias; and, self-report of anxiety, depression, phobic anxiety, and somatization. The demographic analyses were performed initially. Distributions were inspected to determine whether they met underlying statistical assumptions for the subsequent analyses. If the assumptions were met, independent group t tests were performed. When the variances of the groups were not comparable but the distributions were normal, Welch’s t test” was used. Chi square analysis with Yates correction was used to compare lifetime risk of major depression between panic attacks groups and controls.
RESULTS
Table 1 describes the proportion of primary care patients with panic disorder and simple panic as well as a breakdown by sex. The demographic analyses indicated that patients with panic were not significantly different from no-panic controls on age, race, marital status, living situation, number of dependent children in household, or socioeconomic status. The groups were different on gender (x’(4) = 14.14 P < .Ol). The percentages of males in the present and past panic disorder and present simple panic groups were disproportionately low compared to the no disorder group. Because gender could confound subsequent analyses of psychological variables, the analyses were done exclusively on females. Patients with past simple panic had not had an acute panic attack for a median of 9 months (range of 3 months to 11 years) and patients with past panic disorder had not had a panic attack for a median of 9 months (range of 3 months to 10 years). Thirty-one percent of the patients with past simple panic had talked to a physician about their anxiety and 64% of patients with past panic disorder had discussed their nervousness and anxiety with a physician. Only a minority of patients with past panic attacks had been treated with psychoactive medications: 6% of the past simple panic patients had been treated with benzodiazepines and 21% had been treated with antidepressant med;iations; 9% of the past panic disorder patients had been treated with benzodiazepines and 9% had been treated with antidepressant medications. As can be seen in Table 2, the patients with past panic disorder scored significantly higher than the no disorder controls on the SCL-90 Depression, Anxiety. and Phobic-Anxiety Scales and had significantly more phobias than the controls. The patients with past simple panic scored significantly higher than the no disorder controls on the SCL-90 Depression and Anxiety Scale as well as having significantly more phobias than controls. Patients with past simple panic and past panic disorder also had significantly higher lifetime rates of major depression than Table 1. Proportion of Primary Care Sample With Panic Disorder and Simple Panic Diagnosis Present Simple Panic Total sample Females Males
16 16 I1 00.0%) 0 (0.0%)
Past Simple Panic 19 13 (68.4%) 6 (31.6%)
Present Panic Disorder
Past Panic Disorder
26 22 (84.6%) 4 (15.4%)
14 12 (85.7%) 2 (14.3%)
No Disorder 119 78 165.5%) 41 (34.5%)
154
KATON ET AL
Table 2. Means, Standard Deviations, and t Tests of the Psychological and Phobias Across Female Samples
Depression Phobic anxiety Anxiety Total phobias
Simple Panic v No Disorder
Past Panic Disorder vNo Disorder
tt
tS
Simple Panic Past (N = 13)
Past Panic Disorder (N = 12)
No Disorder (N = 78)
M SD M SD
3.2 3.4 40.4 8.0
3.2 4.2 42.3 8.3
2.4 2.5 38.2 6.9
.90 .83
1.68
M SD M SD M SD M SD M SD
59.4 8.5 61.8 8.9 49.2 10.7 60.2 10.1 2.5 1.7
58.4 6.7 62.7 11.0 56.0 11.1 61.3 13.8 3.3 2.5
54.2 9.0 53.7 10.0 45.6 9.0 47.8 9.9 1.4 1.6
1.90
1.48
2.71#
2.75#
1.30
3.47**
4.15”
3.98**
2.031
2.48117
Scale Beck Depression Inventory+ Zung Anxiety Scale SCL-90 Somatization
Tests
.65!$
*Short form. tdf = 86. $df = 85. §df = 12.3 (Welch’s t). 1;; ‘il,(Welch’s t). #P <‘.Ol. l*P < .005.
controls: 1. Twelve of the 13 patients (92.3%) with past simple panic had a lifetime episode of depression v a lifetime risk of 28% in controls (x*(l) = 12.00, P < .OOl) and 2. Eleven of 12 (91.7%) of patients with past panic disorder had a lifetime episode of depression v 28% in controls (x2( 1) = 10.99, P =c .OOl). DISCUSSION
Patients with past panic disorder and past simple panic often had significant symptoms even though they no longer met current criteria for these disorders. Patients with past panic disorder had significantly higher anxiety, phobic anxiety, and depression scores on the XL-90. Patients with past simple panic also had significantly higher SCL-90 anxiety and depression scores than the no disorder controls. Moreover, patients with past panic disorder and past simple panic had significantly more phobias and resultant avoidance behavior as well as a significantly higher lifetime risk of major depression than the no disorder patients. These results are not explained by the presence of major depression because only one patient in each of the past panic subgroups had a current major depressive episode. Hence, despite the fact that their episodes of spontaneous anxiety attacks had ceased, some patients who suffered from panic attacks at one point in their lifetime were still significantly impaired by multiple phobias, avoidance behavior and higher psychological distress especially anxiety and depression. Our findings can be interpreted in two (not necessarily contradictory) ways:
RESIDUAL
SYMPTOMS
OF PANIC DISORDER
155
1. Patients with a past history of panic disorder gradually have decreased acute anxiety attacks over time, but are left with higher levels of psychological distress, multiple phobias, and avoidance behavior. 2. Patients who have suffered from anxiety attacks often have, preceding the attacks, high levels of psychological distress, multiple phobias, avoidance behavior. and are prone to episodes of either panic disorder, major depression, or both when they are faced with stressful life events. Thus, the first interpretation holds that the symptoms we observed in the study were residual symptoms secondary to panic disorder; the second is that patients with panic disorder have an underlying vulnerability (either biological or acquired or both) and are more susceptible to the development of panic disorder and/or major depression when stressed. Because of their lack of panic attacks and the presence of polyphobic/avoidant behavior and high scores on psychological tests of anxiety, the patients with past panic disorder could be categorized by DSM-II I as meeting criteria for agoraphobia without panic disorder, social phobia, or generalized anxiety disorder. If future studies support the hypothesis that panic disorder occurs first and, if left untreated. the panic attacks gradually subside, but phobic behavior and/or generalized anxiety are maintained, then a more accurate description would be panic disorder-residual phase. This term allows that the patient may have an exacerbation of symptoms in the future and that the symptoms have resulted from panic disorder. It is possible that patients with past anxiety attacks may not be currently symptomatic because they have severely constricted their lifestyle in response to the overwhelming anxiety caused by panic disorder. Indeed, if pushed to expand their social interaction, these patients might not only experience anxiety attacks when facing phobic stimuli, but also spontaneous panic A recent study by Uhde et al.‘* supports the first hypothesis, i.e., that pathological anxiety, multiple phobias, and avoidance behavior are secondary to panic disorders and may become residual symptoms after the acute spontaneous panic attacks disappear. Uhde et al. found that 30 of 32 (94%‘) panic disorder patients who developed pathological degrees of generalized anxiety did so after the onset of their first panic attack. Similarly, 31 of 32 patients with agoraphobia developed phobic avoidance behavior after the onset of panic attacks. On the other hand, the Cloninger et al.19 data on the development of panic disorder suggested that generalized anxiety develops early and is followed some years later by panic attacks that occur in the context of generalized anxiety. Klein and colleagues have also shown that patients with panic disorder were more likely to have had problems with severe separation anxiety as children as well as school phobias suggesting longterm vulnerability in some patients with panic disorder.” Two other recent studies supported the notion of long-term vulnerability of panic disorder patients; both of these studies found a significantly higher prevalence rate of traumatic life events (death of a parent or long period of separation from one or both parents) in childhood and adolescence in panic disorder patients than matched controls.“.” In a recent study of the frequency of panic attacks in patients with DSM-III anxiety disorders (agoraphobia with panic, social phobia, simple phobia, panic disorder, generalized anxiety disorder, and obsessive compulsive disorder). Barlow et al.,‘3 found that 83% of individuals in each diagnostic category admitted to having had a panic attack. Moreover, predictable and unpredictable attacks occurred in all
156
KATON ET AL
groups although only patients with panic disorder and agoraphobia with panic had three attacks within a 3-week period. Barlow et al.23 emphasized that patients with social phobias and simple phobias may report a lower frequency of panic because they successfully avoid specific cues or triggers for panic such as bridges or planes. Their notion that avoidance behavior enables patients to decrease the frequency of their panic attacks is similar to the psychoanalytic notion that phobias represent coping mechanisms that bind anxiety attacks into more predictable patterns enabling the patients to have a greater sense of control over their condition. This study did not include longitudinal histories. Therefore, it is unclear whether panic attacks predated the development of anxiety disorders or vice versa. This study does, however, question the notion that panic disorder can be reliably separated from other anxiety disorders. Barlow et alz4 have also reported that the majority of patients with other anxiety disorders (agoraphobia with panic, social phobia, panic disorder, obsessive compulsive disorder) also met criteria for generalized anxiety disorder, again emphasizing the overlap between anxiety disorders. A recent study by Norton et al.25 also supported the findings of the current study. They gave two questionnaires to 186 young college students. Information was obtained on current levels of anxiety and frequency of panic attacks. Their results showed that 34.4% of college students had had a panic attack in the last year, but only 2.2% had three or more panic attacks in the last 3 weeks. Subjects with past panic attacks scored significantly higher on six of the ten SCL-90 subscales, including all those measuring depression and anxiety. Weaknesses of the current study include the relatively small sample of patients and the relatively short median (9 months) time since the last panic attack occurred. Clearly larger samples of patients need to be studied to determine the longitudinal course of psychiatric illness in patients with panic disorder. The above findings, however, do call into question whether the splitting of diagnostic categories into subsets of generalized anxiety, agoraphobia, panic disorder is helpful. Two recent double blind placebo controlled studies of tricyclic antidepressants u benzodiazepines, in patients with generalized anxiety, found the tricyclic antidepressant biologic superior to placebo in efficacy.26*27 These data suggest an underlying similarity between panic disorder and generalized anxiety rather than a difference. Biological tests like the sodium lactate infusion test may help researchers further dissect out similarities and differences between the anxiety disorders. An interesting finding in this study was the striking similarity between patients with past infrequent panic attacks and patients who met DSM-III creiteria for past panic disorder. Both had significantly higher XL-90 anxiety and depression scores than controls as well as a significantly higher total number of phobias and a similar high risk (92%) of lifetime major depressive episodes. Past studies by Von Korff et between al.,28 Norton et al.,25 and Katon et al.” have all supported similarities infrequent panickers and controls on demograph variables (age and sex), psychological profiles on the SCL-90, and Iifetime risk of affective illness. In addition, recent that both patients studies by Dager et al.,29 and Cowley et al.,30 have determined with infrequent panic attacks and patients with panic disorder have significantly higher rates of mitral valve prolapse (MVP) and positive lactate infusion tests than normals. However, they found no difference in prevalence of MVP and positive lactate infusion tests between the patients with infrequent panic attacks and those with panic disorder. The data suggests that rather than a clear demarcation between
RESIDUAL
SYMPTOMS
157
OF PANIC DISORDER
patients with panic disorder as defined by DSM-III and patients with infrequent panic attacks, there is a spectrum of severity of panic disorder.3’ REFERENCES 1. Keller MB, Shapiro
RW: “Double
depression”:
Superimposition
chronic depressive disorders. Am J Psychiatry 139:4388442, 1982 2. Akiskal HS, Rosenthal TL, Radwan F, et al: Characterological EEG findings separating subaffective dysthymias from “Character
of acute depressive
episodes
on
depressions: Clinical and sleep spectrum disorders.” Arch Gen
Psychiatry 37:777-783, 1980 3. Wheeler EO, White PD, Reed EW, et al: Nemo-circulatory asthenia (anxiety neurosis, effort syndrome, neurasthenia): A twenty year follow-up study of one hundred and seventy-three patients. JAMA 142:878-889, 1950 4. Marks I, Lader M: Anxiety states (anxiety neurosis): A review. J Nerv Ment Dis 156:3-l 8. 1973 5. Noyes R, Clancy J, Hoenk PR, et al: The prognosis of anxiety neurosis. Arch Gen Psychiatry 37:173-178, 1980 6. Greer HS: The prognosis of anxiety states, in Lader MD (ed): Studies in Anxiety. London. Royal Medico-Psychological Association, 1969, pp 151-157 7. Breier A, Charney DS, Heninger GB: Major depression in patients with agoraphobia and panic disorder.ArchGenPsychiatry41:1129~1135. 1984 8. Kendell RE: The stability of psychiatric diagnoses. Br J Psychiatry I24:352~356. I974 9. Tyrer P: Neurosis divisible. Lancet I: 685-688. 1984 IO. Klein DF: Anxiety reconceptualized. Compr Psychiatry 2 I :4 I I, 1980 I 1. Katon W, Vitaliano PP. Russo J, et al: Panic disorder: Epidemiology in primary care. J Fam Pratt 23:233-239, 1986 12. Robins LN, Helzer JE, Croughan J. et al: National Institute of Mental Health Diagnostic Interview Schedule: Its history, characteristics and validity. Arch Gen Psychiatry 38:38 l-389, I98 I 13. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (ed 3). Washington, DC, American Psychiatric Association, 1980 14. Beck AT, Beck RW: Screening depressed patients in family practice: A rapid technique. Postgrad Med 12:81-85, 1972 15. Zung WWK: A rating instrument for anxiety disorders. Psychosomatics 12:371-379, 1975 16. Derogatis LR: SCL-90R Manual. Baltimore, Clinical Psychometric Research, 1977 17. Welch BL: The significance of the difference between two means when the population variances are unequal. Biometrika 29:350-362, 1938 i 8. Uhde TW, Bowlenger J, Roy-Byrne PP, et al: Longitudinal course of panic disorder: Clinical and biological considerations. Prog Neuropsychopharmacol Biol Psychiatry 9:39-51. 1985 19. Cloninger CR, Martin RL, Clayton P. et al: A blind follow-up and family study of anxiety neurosis; Preliminary analysis of the St Louis 500, in Klein DF, Rabkin J (eds): Anxiety: New Research and Changing Concepts. New York, Raven, I98 I, pp 137-l 48 20. Klein DF: Anxiety reconceptualized: Early experiences with imipramine and anxiety. Compr Psychiatry 21:4l l-427, 1980 21. Faravelli C, Weff T. Ambonetti A, et al: Prevalence of traumatic early life events in 31 agoraphobic patients with panic attacks. Am J Psychiatry 142:1493-l 494, 1985 22. Raskin M. Peeke HVS, Dickman W, et al: Panic and generalized anxiety disorders: Developmental antecedents and precipitants. Arch Gen Psychiatry 39:587-589, 1982. 23. Barlow DH, Vermilyea J. Blanchard EB, et al: The phenomenon of panic. J Abnorm Psycho1 94:32@-328, 1985 24. Barlow DH, Blanchard EB. Vermilyea J. et al: Generalized anxiety and generalized anxiety disorder: Description and reconceptualization. Am J Psychiatry 143:40-44, 1986 25. Norton GR, Harrison B, Hauch J. et al: Characteristics of people with infrequent panic attacks. J Agn Psychiatry 94:216-221, 1985 26. Johnstone EC. Cunningham 0, Frith CD: Neurotic illness and its response to anxiolytic and antidepressant treatment. Psycho1 Med IO:321 -328, 1980 27. Kahn RJ, McNair DM. Lipman RS: Imipramine and chlordiazepoxide in depressive and anxiety disorders. II. Efficacy in anxious outpatients. Arch Gen Psychiatry 43:79-85, 1986
158
KATON ET AL
28. Von Korff MR, Eaton WW, Key1 P: The epidemiology of panic attacks and panic disorder: Results of three community surveys. Am J Epidemiol 122:970-98 1, 1985 29. Dager SR, Comess KA, Dunner DL: Differentiation of anxious patients by 2D-echocardiographic evaluation of the mitral valve. Am J Psychiatry 143:533-535, 1986 30. Cowley D, Dager S, Foster S, et al: Clinical characteristics and response to sodium lactate in patients with infrequent panic attacks. Am J Psychiatry (in press) 31. Katon W, Vitaliano P, Russo J, et al: Panic disorder: Spectrum of severity and somatization. J Nerv Ment Dis (in press)
After the
Wayne Katon, Peter P. Vitaliano, Kathleen Anderson, Michael Jones, and Joan Russo Patients attacks
with
a past history
were compared
panic attacks
had significantly
as significantly suffered
more
anxiety
needs to be focused of the relationship
and avoidance
Like patients
with
symptoms
on the longitudinal
disorder
the controls
with
episodes
anxiety
with past
tests, as well
who
had never
of superimposed
who recover from panic disorder,
depression,
and phobias.
course of panic disorder in order to enhance
among the anxiety disorders (generalized
by Grune & Stratton,
than
acute
Patients
scores on psychological
of patients
of anxiety,
from
anxiety attacks.
behavior,
dysthymic
to be a subgroup
residual
panic disorder) as well as major affective B 1987
no longer suffering
higher anxiety and depression
there appears
significant
who were
who had never experienced
social phobias
attacks.
major depression, are left with
of panic disorder
to patients
More
but
research
understanding
anxiety, social phobia, agoraphobic,
and
disorder.
Inc.
I
YEARS, Keller and colleagues have developed the concept of N RECENT as the superimposition of acute depressive episodes on “double depression” chronic depressive disorder.’ Akiskal et al.’ have also noted that dysthymic disorder is often complicated by superimposed major depressive episodes. Although anxiety disorders are also quite common in the general population, few epidemiological studies have studied the longitudinal course of anxiety disorders such as panic disorder. Panic disorder tends to be a relapsing, remitting disorder. Studies that have reevaluated patients with panic disorder up to 20 years after initial diagnosis found that 50% had some level of disability and 73%) to 93% were symptomatic.‘-” Patients with panic disorder are also at high risk for the development of major depression, agoraphobia, and generalized anxiety.‘,’ The separation of anxiety from depression is particularly difficult with frequent “crossing over” from one diagnosis to the other.‘k9 Anxiety states frequently change to depressive illness, depression is a common complication of agoraphobia and panic disorder and generalized anxiety often increases in the course of panic disorder.7,8.‘0 Although studies have documented that many patients who develop major depression have had longterm problems with dysthymic disorder and that, if left untreated, they often continue to have chronic depressive symptoms, less is known about the longterm course of panic disorder.‘.2 Once there has been a remission of the acute panic attacks, do the patients’ symptoms of anxiety and depression cease, or as in depression, do patients have chronic anxiety and depressive symptoms that are subclinical, but apt to exacerbate during stressful life events? Tyrer has suggested that although patients with panic disorder may have complete resolution of the acute anxiety in the short term, both anxiety and minor depression usually persist.’ In fact, Tyrer’ has coined the term “the general neurotic syndrome” to From the Division of Consultation and Liaison Psychiaq. University of Washington Medical School, Seattle. Address reprint requests io Wayne Katon, M.D., Associate Professor, lJniversit_v of Washington Medical School, Psychiatry and Behavioral Sciences RP-I 0, Seattle. WA 98195. 0 I987 by Grune & Stratton, Inc. 0010-440X/87/2802-0006$03.00/0 Comprehensive
Psychiaby,
Vol. 28,
No. 2 (March/April),
1987:
pp 15 1- 158
151
152
KATON
ET AL
classify patients who pass “chameleon-like through different diagnostic hues depending on the nature of the stressors they encounter.” Tyrer emphasized the changeable nature of this syndrome, noting that patients have agoraphobia, social phobias, panic disorder, generalized anxiety, and hypochondriasis during their life course. Sometimes only one or two illnesses are present, sometimes all. The purpose of this study was to examine the present symptomatology of patients with a history of past panic disorder as compared to patients who have never suffered from anxiety attacks. The central hypothesis tested was that patients who suffered from panic disorder in the past but who had not had a panic attack for at least 3 months would have higher scores than controls on psychological tests of anxiety, depression, and somatization as well as having significantly more social phobias and avoidance behavior. METHOD Subjects were selected from the University
of Washington
Family Medical Center (Seattle)
a primary
care facility which, similar to other primary care practices, routinely sees a high percentage of anxiety/depression cases. The Family Medical Center is an outpatient clinic with 7,000 registered patients and 19,000 outpatient visits annually. It is staffed by 30 residents and faculty physicians. The ratio of female to male visits is 2.5 to one. In this university family medical practice, 195 randomly selected primary care patients 17 years of age and over, who were coming in to the primary care physician for a routine symptomatic visit” were given a modified form of the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule (DE)‘* by two trained interviewers (KA was a senior psychiatry resident, MJ was a medical student). Prior to the study, both interviewers were trained in the use of the DIS by the senior author (WK), who has utilized the DIS in multiple past studies and received training from the University of Washington psychiatrists who were taught the interview in St Louis. Training in the use of the interview included direct observation of the experienced interviewer, direct supervision of the research interviews, and interrater trials. In addition, 10% of the interviews were completed and independently scored by both interviewers and they were in almost complete agreement in the classification of panic disorder (Kappa = .90, P < ,006). Patients who had a history of panic attacks with at least four somatic symptoms were interviewed further in order to screen for alcohol abuse/ dependence and major depression. One out of every four patients who did not meet criteria for panic disorder was screened for major depression and alcohol abuse; the other three out of four were not further screened by interviewers. Patients were classified as having panic disorder, major depression, and/or alcohol abuse utilizing Diagnostic and Statistical Manual of Mental Disorders (ed 3) (DSM-III) criteria.” The cutoff point in DSM-III criteria for panic disorder requires that patients must have three panic attacks in a 3-week period and at least four autonomic symptoms occurring during an attack. An additional diagnosis was added (and termed simple panic) for patients who fulfilled the criteria of acute anxiety attacks that included four or more autonomic symptoms, but who had less than three attacks in a 3-week period. Patients who suffered from panic disorder or simple panic, but who had not had symptoms for 3 or more months were labeled as having past panic disorder or past simple panic.
Subjects The 195 patients (53 male and 142 female) ranged in age from 17 to 84 years with a mean of 37.2 and a median of 33.6 years. Ninety-six patients were married, 67 were never married, and 3 1 were separated, divorced, or widowed. There were 176 Caucasian, 11 black, four Hispanic, and four Asian patients. In terms of Hollingshead social class index, 1.7% of patients were from social class I, 14.4% were from social class II, 46% were from social class III, 23.6% were from social class IV, and 14.4% were from social class V. Of the patients approached for the study, 53% consented to be interviewed. Compared with the norms of the clinic population, there were no significant differences in age, ratio of female-to-male patients’ visits to the clinic, race, or socioeconomic status.
Measures
and Statistical
Analyses
In order to help validate the diagnostic findings, patients were asked to complete a battery of psychological tests including the Beck Depression Inventory (short form),14 Zung Anxiety Scale (SAS),”
RESIDUAL
SYMPTOMS
and the SCL-90
OF PANIC
153
DISORDER
subscales on Depression,
Anxiety,
Phobic-Anxiety,
Somatization.
and Additional
Items.”
Major analyses compared primary care patients with and without panic disorder. Comparisons were made on demographic variables; presence of coexisting diagnoses of depression or alcoholism; help seeking behavior; number of phobias; and, self-report of anxiety, depression, phobic anxiety, and somatization. The demographic analyses were performed initially. Distributions were inspected to determine whether they met underlying statistical assumptions for the subsequent analyses. If the assumptions were met, independent group t tests were performed. When the variances of the groups were not comparable but the distributions were normal, Welch’s t test” was used. Chi square analysis with Yates correction was used to compare lifetime risk of major depression between panic attacks groups and controls.
RESULTS
Table 1 describes the proportion of primary care patients with panic disorder and simple panic as well as a breakdown by sex. The demographic analyses indicated that patients with panic were not significantly different from no-panic controls on age, race, marital status, living situation, number of dependent children in household, or socioeconomic status. The groups were different on gender (x’(4) = 14.14 P < .Ol). The percentages of males in the present and past panic disorder and present simple panic groups were disproportionately low compared to the no disorder group. Because gender could confound subsequent analyses of psychological variables, the analyses were done exclusively on females. Patients with past simple panic had not had an acute panic attack for a median of 9 months (range of 3 months to 11 years) and patients with past panic disorder had not had a panic attack for a median of 9 months (range of 3 months to 10 years). Thirty-one percent of the patients with past simple panic had talked to a physician about their anxiety and 64% of patients with past panic disorder had discussed their nervousness and anxiety with a physician. Only a minority of patients with past panic attacks had been treated with psychoactive medications: 6% of the past simple panic patients had been treated with benzodiazepines and 21% had been treated with antidepressant med;iations; 9% of the past panic disorder patients had been treated with benzodiazepines and 9% had been treated with antidepressant medications. As can be seen in Table 2, the patients with past panic disorder scored significantly higher than the no disorder controls on the SCL-90 Depression, Anxiety. and Phobic-Anxiety Scales and had significantly more phobias than the controls. The patients with past simple panic scored significantly higher than the no disorder controls on the SCL-90 Depression and Anxiety Scale as well as having significantly more phobias than controls. Patients with past simple panic and past panic disorder also had significantly higher lifetime rates of major depression than Table 1. Proportion of Primary Care Sample With Panic Disorder and Simple Panic Diagnosis Present Simple Panic Total sample Females Males
16 16 I1 00.0%) 0 (0.0%)
Past Simple Panic 19 13 (68.4%) 6 (31.6%)
Present Panic Disorder
Past Panic Disorder
26 22 (84.6%) 4 (15.4%)
14 12 (85.7%) 2 (14.3%)
No Disorder 119 78 165.5%) 41 (34.5%)
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Table 2. Means, Standard Deviations, and t Tests of the Psychological and Phobias Across Female Samples
Depression Phobic anxiety Anxiety Total phobias
Simple Panic v No Disorder
Past Panic Disorder vNo Disorder
tt
tS
Simple Panic Past (N = 13)
Past Panic Disorder (N = 12)
No Disorder (N = 78)
M SD M SD
3.2 3.4 40.4 8.0
3.2 4.2 42.3 8.3
2.4 2.5 38.2 6.9
.90 .83
1.68
M SD M SD M SD M SD M SD
59.4 8.5 61.8 8.9 49.2 10.7 60.2 10.1 2.5 1.7
58.4 6.7 62.7 11.0 56.0 11.1 61.3 13.8 3.3 2.5
54.2 9.0 53.7 10.0 45.6 9.0 47.8 9.9 1.4 1.6
1.90
1.48
2.71#
2.75#
1.30
3.47**
4.15”
3.98**
2.031
2.48117
Scale Beck Depression Inventory+ Zung Anxiety Scale SCL-90 Somatization
Tests
.65!$
*Short form. tdf = 86. $df = 85. §df = 12.3 (Welch’s t). 1;; ‘il,(Welch’s t). #P <‘.Ol. l*P < .005.
controls: 1. Twelve of the 13 patients (92.3%) with past simple panic had a lifetime episode of depression v a lifetime risk of 28% in controls (x*(l) = 12.00, P < .OOl) and 2. Eleven of 12 (91.7%) of patients with past panic disorder had a lifetime episode of depression v 28% in controls (x2( 1) = 10.99, P =c .OOl). DISCUSSION
Patients with past panic disorder and past simple panic often had significant symptoms even though they no longer met current criteria for these disorders. Patients with past panic disorder had significantly higher anxiety, phobic anxiety, and depression scores on the XL-90. Patients with past simple panic also had significantly higher SCL-90 anxiety and depression scores than the no disorder controls. Moreover, patients with past panic disorder and past simple panic had significantly more phobias and resultant avoidance behavior as well as a significantly higher lifetime risk of major depression than the no disorder patients. These results are not explained by the presence of major depression because only one patient in each of the past panic subgroups had a current major depressive episode. Hence, despite the fact that their episodes of spontaneous anxiety attacks had ceased, some patients who suffered from panic attacks at one point in their lifetime were still significantly impaired by multiple phobias, avoidance behavior and higher psychological distress especially anxiety and depression. Our findings can be interpreted in two (not necessarily contradictory) ways:
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1. Patients with a past history of panic disorder gradually have decreased acute anxiety attacks over time, but are left with higher levels of psychological distress, multiple phobias, and avoidance behavior. 2. Patients who have suffered from anxiety attacks often have, preceding the attacks, high levels of psychological distress, multiple phobias, avoidance behavior. and are prone to episodes of either panic disorder, major depression, or both when they are faced with stressful life events. Thus, the first interpretation holds that the symptoms we observed in the study were residual symptoms secondary to panic disorder; the second is that patients with panic disorder have an underlying vulnerability (either biological or acquired or both) and are more susceptible to the development of panic disorder and/or major depression when stressed. Because of their lack of panic attacks and the presence of polyphobic/avoidant behavior and high scores on psychological tests of anxiety, the patients with past panic disorder could be categorized by DSM-II I as meeting criteria for agoraphobia without panic disorder, social phobia, or generalized anxiety disorder. If future studies support the hypothesis that panic disorder occurs first and, if left untreated. the panic attacks gradually subside, but phobic behavior and/or generalized anxiety are maintained, then a more accurate description would be panic disorder-residual phase. This term allows that the patient may have an exacerbation of symptoms in the future and that the symptoms have resulted from panic disorder. It is possible that patients with past anxiety attacks may not be currently symptomatic because they have severely constricted their lifestyle in response to the overwhelming anxiety caused by panic disorder. Indeed, if pushed to expand their social interaction, these patients might not only experience anxiety attacks when facing phobic stimuli, but also spontaneous panic A recent study by Uhde et al.‘* supports the first hypothesis, i.e., that pathological anxiety, multiple phobias, and avoidance behavior are secondary to panic disorders and may become residual symptoms after the acute spontaneous panic attacks disappear. Uhde et al. found that 30 of 32 (94%‘) panic disorder patients who developed pathological degrees of generalized anxiety did so after the onset of their first panic attack. Similarly, 31 of 32 patients with agoraphobia developed phobic avoidance behavior after the onset of panic attacks. On the other hand, the Cloninger et al.19 data on the development of panic disorder suggested that generalized anxiety develops early and is followed some years later by panic attacks that occur in the context of generalized anxiety. Klein and colleagues have also shown that patients with panic disorder were more likely to have had problems with severe separation anxiety as children as well as school phobias suggesting longterm vulnerability in some patients with panic disorder.” Two other recent studies supported the notion of long-term vulnerability of panic disorder patients; both of these studies found a significantly higher prevalence rate of traumatic life events (death of a parent or long period of separation from one or both parents) in childhood and adolescence in panic disorder patients than matched controls.“.” In a recent study of the frequency of panic attacks in patients with DSM-III anxiety disorders (agoraphobia with panic, social phobia, simple phobia, panic disorder, generalized anxiety disorder, and obsessive compulsive disorder). Barlow et al.,‘3 found that 83% of individuals in each diagnostic category admitted to having had a panic attack. Moreover, predictable and unpredictable attacks occurred in all
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groups although only patients with panic disorder and agoraphobia with panic had three attacks within a 3-week period. Barlow et al.23 emphasized that patients with social phobias and simple phobias may report a lower frequency of panic because they successfully avoid specific cues or triggers for panic such as bridges or planes. Their notion that avoidance behavior enables patients to decrease the frequency of their panic attacks is similar to the psychoanalytic notion that phobias represent coping mechanisms that bind anxiety attacks into more predictable patterns enabling the patients to have a greater sense of control over their condition. This study did not include longitudinal histories. Therefore, it is unclear whether panic attacks predated the development of anxiety disorders or vice versa. This study does, however, question the notion that panic disorder can be reliably separated from other anxiety disorders. Barlow et alz4 have also reported that the majority of patients with other anxiety disorders (agoraphobia with panic, social phobia, panic disorder, obsessive compulsive disorder) also met criteria for generalized anxiety disorder, again emphasizing the overlap between anxiety disorders. A recent study by Norton et al.25 also supported the findings of the current study. They gave two questionnaires to 186 young college students. Information was obtained on current levels of anxiety and frequency of panic attacks. Their results showed that 34.4% of college students had had a panic attack in the last year, but only 2.2% had three or more panic attacks in the last 3 weeks. Subjects with past panic attacks scored significantly higher on six of the ten SCL-90 subscales, including all those measuring depression and anxiety. Weaknesses of the current study include the relatively small sample of patients and the relatively short median (9 months) time since the last panic attack occurred. Clearly larger samples of patients need to be studied to determine the longitudinal course of psychiatric illness in patients with panic disorder. The above findings, however, do call into question whether the splitting of diagnostic categories into subsets of generalized anxiety, agoraphobia, panic disorder is helpful. Two recent double blind placebo controlled studies of tricyclic antidepressants u benzodiazepines, in patients with generalized anxiety, found the tricyclic antidepressant biologic superior to placebo in efficacy.26*27 These data suggest an underlying similarity between panic disorder and generalized anxiety rather than a difference. Biological tests like the sodium lactate infusion test may help researchers further dissect out similarities and differences between the anxiety disorders. An interesting finding in this study was the striking similarity between patients with past infrequent panic attacks and patients who met DSM-III creiteria for past panic disorder. Both had significantly higher XL-90 anxiety and depression scores than controls as well as a significantly higher total number of phobias and a similar high risk (92%) of lifetime major depressive episodes. Past studies by Von Korff et between al.,28 Norton et al.,25 and Katon et al.” have all supported similarities infrequent panickers and controls on demograph variables (age and sex), psychological profiles on the SCL-90, and Iifetime risk of affective illness. In addition, recent that both patients studies by Dager et al.,29 and Cowley et al.,30 have determined with infrequent panic attacks and patients with panic disorder have significantly higher rates of mitral valve prolapse (MVP) and positive lactate infusion tests than normals. However, they found no difference in prevalence of MVP and positive lactate infusion tests between the patients with infrequent panic attacks and those with panic disorder. The data suggests that rather than a clear demarcation between
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