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Classic Conditioning and Dysfunctional Cognitions in Patients With Panic Disorder and Agoraphobia Treated With an Implantable Cardioverter/Defibrillator

From the Departments of Psychiatry (F.G., B.A., R.B., C.G., M.L.) and Cardiology (S.B., F.L.), Free University of Berlin, Berlin, Germany.

Address reprint request to: Dr. Frank Godemann, Hindenburgdamm 30, 12200 Berlin, Germany. Email: godemann{at}zedat fu-berlin.de

	ABSTRACT

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OBJECTIVE: A model for the development of anxiety disorders (panic disorder with or without agoraphobia) is needed. Patients with an implantable cardioverter/defibrillator (ICD) are exposed to repeated electric shocks. If the theory of anxiety development by aversive classic conditioning processes is valid, these repeated shocks should lead to an increased risk of anxiety disorders. To study this hypothesis, we retrospectively studied 72 patients after implantation of an automatic ICD.

METHODS: Patients were assessed with the semistructured Diagnostic Interview of Psychiatric Disease 1 to 6 years after implantation of an automatic ICD. Panic disorder and/or agoraphobia was diagnosed in patients who fulfilled all DSM-III-R criteria for those conditions.

RESULTS: Anxiety disorder developed in 15.9% of patients after ICD implantation. This was significantly related to the frequency of repeated defibrillation (shocks) to stop malignant ventricular arrhythmias. Dysfunctional cognitions are an additional vulnerability factor.

CONCLUSIONS: The data support both the conditioning hypothesis and the cognitive model of anxiety development. These findings suggest that ICD patients are an appropriate risk population for a prospective study of the development of anxiety disorders.

Key Words: implantable cardioverter/defibrillator • panic disorder • agoraphobia.

Abbreviations: DIPS = Diagnostic Interview of Psychiatric Disease; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, third edition revised; ICD = implantable cardioverter/defibrillator; PTSD = posttraumatic stress disorder; SAD = subthreshold anxiety disorder; SCL-90-R = revised Symptom Checklist 90.

	INTRODUCTION

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Panic disorders and/or agoraphobia have a lifetime prevalence of 2.5% to 3% (1, 2) and are thus epidemiologically prominent among psychiatric disorders. Convincing findings and plausible theories on the development and maintenance of anxiety disturbances exist. Apart from biological (3, 4) and genetic findings (5), many results point to classic conditioning processes and dysfunctional cognitions as vulnerability factors for panic disorders and/or agoraphobia (6–9).

A comprehensive uniform theoretical model is not yet available for the development of panic disorders and phobias. Reinicker (10) points out that the conditions under which phobias develop cannot be determined either generally or individually because no observers are present when they develop. Research thus far has led to a theoretical pluralism in which learning theory–based conditioning models and cognitive theories play an important role.

Mowrer (11) explained in the two-factor theory that situations that definitely trigger an anxiety reaction (eg, innate ones) become linked to neutral stimuli within the context of spatial and temporal association and can then evoke an anxiety reaction by themselves. This process is known as classic conditioning. These learned anxiety reactions are subject to habituation unless there is subsequent avoidance behavior. Avoidance would maintain the anxiety reaction by acting as a negative reinforcement under an operant conditioning paradigm.

Retrospective interviews point to conditioning experiences as triggering factors in nearly 90% of agoraphobia cases (12). In addition, there have been positive findings from aversion therapy. Here aversive avoidance reactions to the target stimulus (eg, drugs) result from the respective conditioning processes (13, 14).

During panic attacks, patients interpret their bodily sensations as a catastrophic event (7, 10, 15). Moreover, Lazarus (16) points out that people are always appraising their coping options for overcoming dangers. Ehlers et al. (9) emphasize selective focusing on normal interoceptive stimuli (eg, heart beat). This altered perception does not correspond to any real improvement in the ability to appraise bodily changes (17).

Beck et al. (6) indicate that the physical experience of anxiety becomes a personal threat. In conjunction with readiness reactions, these fears lead to psychophysiological changes (eg, hyperventilation and tachycardia), which in turn confirm the anxieties and reinforce the fears. According to behavioral theories, an attempt is then made to interrupt this vicious circle by avoiding outer and inner stimuli.

These theories are based on individual case observations, observations of subjects with chemically induced panic attacks (9, 17), and control group examinations (patients with panic disorders vs. healthy, depressive, and somatically ill patients) (18–20). However, it has not yet been possible to test or develop these theories in a prospective manner. The estimated incidence of these disorders is too low (approximately 0.1%) (21) for a prospective investigation. Therefore, it would be of great scientific value to identify a high-risk population with an incidence high enough to warrant a prospective study.

Somatic conditions cause sufficient stress to trigger frequent panic attacks, which may lead to the development of an anxiety disorder. Such an increased prevalence of panic attacks and anxiety disorders has been reported in conjunction with various somatic conditions. Particularly high risk seems to be associated with conditions whose clinical symptoms coincide to some extent with those of the panic attack (eg, palpitations, vertigo, and dyspnea). Thus, an increased incidence of anxiety disorders is found in patients with lung diseases (8, 22–25), heart diseases (angina pectoris) (26), and vestibular disorders (27, 28).

Implantation of an ICD for treatment of malignant ventricular arrhythmias is also known to be associated with an increased risk of anxiety (29–31) and anxiety disorders (32). The short-term release of high energy by an ICD is an effective technique for stopping life-threatening arrhythmias (33, 34). Mortality can be markedly reduced by this therapy compared with pharmacological antiarrhythmic treatment (35, 36). On the other hand, this therapy involves the application of a repeated, uncontrolled, irregular, and very aversive stimulus. Theoretically it should, in terms of an unconditioned stimulus, lead to an unconditioned reaction with the development of a conditioned stimulus and conditioned reaction. The development of phobia mediated by anticipatory cognitions would then cause preventive avoidance behavior. Progressive avoidance behavior could then result in agoraphobia.

However, the literature does not provide adequate information on the incidence of anxiety disorders after implantation of an ICD. Chevalier et al. (37) reported a 20% prevalence in 30 patients, but they did not provide data indicating when the anxiety disorders developed. Moreover, generalized anxiety disorder was diagnosed in four of the six patients. Morris et al. (38) found one case of panic disorder among 20 patients with an ICD. About 50% had some type of psychiatric disorder. Bourke et al. (39) reported three cases of agoraphobia and panic disorder among 35 ICD patients. All other authors have reported only individual cases (40, 41) or have assessed anxiety by using self-ratings (29, 42, 43).

We examined the prevalence and particularly the incidence of panic disorders and/or agoraphobia in 72 patients after ICD implantation to determine whether these somatically affected patients represent a high-risk population for the development of anxiety disorders.

	METHODS

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ICD implantation has been performed in the Department of Cardiology at the University Hospital Benjamin Franklin since 1989. About 250 patients are currently involved in the outpatient follow-up program to monitor ICD function and to make readjustments. A semistructured interview (DIPS) (44) was used to assess all available patients (local residents) who provided informed consent and who were considered to be intellectually and physically fit for participation. The interview, which focuses on the diagnosis of anxiety disorders, registers both the presence of a mental disorder and the time at which it developed. Three patients whose anxiety disorders had developed before ICD implantation were excluded from the statistical analysis. In addition, avoidance behavior and anxiety level were measured with the SCL-90-R (45).

Sixty-one of the 250 patients were excluded (not assessed) because they lived outside Berlin, as were 11 others who had speech, intellectual, or physical restrictions. Nineteen patients agreed to participate but then could not be reached by phone. Five patients were excluded at the request of the Department of Cardiology. Another 46 patients were excluded because their ICD had been implanted for <1 year.

Of the remaining 108 patients, 36 refused to be interviewed. Two of these patients reported that their great fear of leaving the house since implantation of the ICD would prevent them from appearing for an additional examination. Thus, a total of 72 patients were assessed.

Apart from the psychiatric diagnosis, a 10-item self-assessment scale was used to record the mode of cognitive coping with shocks experienced to identify variables that are more frequent in patients with anxiety disorders after ICD implantation. Patients specified the extent of their agreement with various statements using a five-point Likert scale ("do not agree" to "agree fully"). The items were selected with reference to the most important cognitive theories of panic disorder (including increased self-observation and catastrophic thoughts). Forty-eight patients with at least one ICD discharge filled out this questionnaire. We developed this questionnaire specifically for this study and preferred it to others, such as the Agoraphobic Cognitions Questionnaire (46), which we think lack specificity in relation to experienced shocks. We also recorded the severity of cardiac insufficiency as indicated by the New York Heart Association classification, which ranges from I (no discomfort with normal stress) to IV (dyspnea at rest); left ventricular ejection fraction; and the number of shocks delivered by the ICD.

	RESULTS

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The patient sample comprised 62 men and 10 women with a mean age of 69.1 (SD = 10.4) years. Mean ejection fraction was 43% (SD = 16.2%). The severity of cardiac insufficiency (New York Heart Association classification) was as follows: no signs of cardiac insufficiency, 2 patients; class II, 14 patients; class III, 45 patients; and class IV, 11 patients. The 28 patients who declined to participate in the interview did not differ significantly from participants in age, ejection fraction, or number of shocks.

Prevalence and Incidence of Panic Disorders and Agoraphobia
Fourteen patients (19.4%) fulfilled the criteria for agoraphobia and/or panic disorder. In 3 of these 14 patients, the anxiety disorder had developed before ICD implantation. There were clear indications that the anxiety disorder had started to develop during the first year after implantation in the remaining 11 of 69 patients (15.9%). These patients showed a significantly higher phobic avoidance (p < .001) but did not have a significantly higher anxiety level on the SCL-90-R (43). Patients with anxiety disorders were significantly younger (p < .05). In addition, a newly developed subdiagnostic anxiety disorder was observed in 10 patients. This subthreshold group included patients who had dysfunctional avoidance but lacked one of the DSM-III-R criteria for panic disorder or agoraphobia (47). This could mean, for example, that the patients no longer made phone calls because they had experienced a shock during a telephone conversation. Avoidance of flights or sexual intercourse, for example, was not counted because physicians’ recommendations for flights differ and because sexual activity can considerably increase the pulse rate, which can trigger the defibrillator in some patients. Of the 11 patients with anxiety disorder, 1 fulfilled the criteria of a depressive disorder; 2, of a social phobia; and 3, of a specific phobia. Among the 58 patients without anxiety disorder, these criteria were fulfilled by 4, 0, and 3 patients, respectively. All the specific phobias developed before ICD implantation.

Physiological and Psychological Features in Patients With Agoraphobia and Panic Disorder After ICD Implantation
ICD shocks occurred in 48 of 69 patients during follow-up. A comparison of ICD patients with and without panic disorders and/or agoraphobia according to DSM-III-R criteria ( Table 1) showed that patients with anxiety disorder had a significantly higher rate of ICD shocks, defibrillation episodes, and shock clusters. A defibrillation episode was defined as a tachyarrhythmic episode in which one or more ICD shocks were delivered and lasted until the patient was free from additional ICD shocks for at least 1 hour (48). A shock cluster is defined as more than five discharges within 24 hours. On the other hand, there were no significant differences with respect to the severity of cardiac insufficiency. Resuscitated patients had significantly fewer anxiety disorders than patients who received an ICD for other reasons. Resuscitated patients did not regard ICD discharge as a sign of security (resuscitated patients: mean = 3.3, SD = 1.5; patients with syncope or ventricular tachycardia: mean = 3.2, SD = 1.6; t = 1.25, p = .217).

The logistic regression analysis ( Table 3) of variables found to be significant on univariate testing revealed a considerably increased risk for the development of anxiety disorders in patients who have a high concern with their own body (odds ratio = 3.3) and experience a great number of discharge clusters (odds ratio = 3.7). Patients were correctly assigned to the groups with and without anxiety disorders in 89.1% of the cases. Sex, resuscitation experience, and severity of cardiac insufficiency were not significant in this model. The bivariate correlation of subjective concern with the body and the number of clusters was likewise not significant (r = 0.24, Spearman).

	DISCUSSION

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In the 69 ICD patients examined, the significant relation between anxiety and the frequency of shocks and shock clusters supports the role of classic conditioning in the development of panic disorders and agoraphobia. Shocks are a sudden aversive stimulus for ICD patients. A perceived increase of the pulse or irregularities are recognized by patients as premonitory signs. The shock is painful and thus jeopardizes the patients’ feelings of security. Thus, accessory anxiety symptoms frequently develop after the shock. Malignant tachycardias interrupted by the shock are sometimes accompanied by a brief loss of consciousness. This can be experienced by the patient as a loss of control. As in classic conditioning, the psychovegetative anxiety reaction may become connected with formerly neutral stimuli, which can then evoke anxiety symptoms even in the absence of the original stressor. These stimuli are then avoided (operant conditioning), and agoraphobic symptoms can thus develop (eg, a patient refuses to use a telephone after a shock was delivered during a phone call). Also, the ICD discharges can trigger dysfunctional catastrophic cognitions about the meaning of threatening life events and situations or the consequences of experienced symptoms.

Reports in the literature about the effect of discharges on anxiety are contradictory. Schöhl et al. (50) and Herrmann et al. (29) found an association between anxiety after ICD implantation and the experience of shocks. In contrast, Chevalier et al. (37) reported no difference in anxiety levels between shocked and nonshocked ICD patients. Pauli et al. (42) likewise found no relation between the number of shocks per year and the level of anxiety, but they did find a clear relation to the catastrophic fear of dying (p = .001). They concluded that classic conditioning plays a subordinate role in anxiogenesis. Differences between our own findings and those published in the literature can be partially explained by the fact that an average of only 2.5 shocks were recorded in the 61 patients studied by Pauli et al. (42), compared with 8.2 in our 69 patients. The interpretation of these findings is limited because the number of shocks per year is lower in our sample. In contrast, Dunbar et al. (51) reported that anxious patients more often have arrhythmia events. Thus, there seems to be a complex interaction between shocks and anxiety symptoms. It must be stressed, however, that this finding cannot explain the development of complex diseases like anxiety disorders. Being anxious may possibly be a risk factor for both arrhythmic events and anxiety disorders.

Shock clusters put patients under high psychological stress. Thus, shock clusters occurred five times more frequently in patients with anxiety disorders than in those without them. Hamner et al. (52) presented three case reports on ICD patients with PTSD. Because clusters of shocks are an extreme experience for patients, it is remarkable that in our group, only one ICD patient reported marked hypervigilance and nocturnal wakening as occurs with PTSD. It is also interesting that a significantly lower number of resuscitated patients developed anxiety disorders, which may be due to the fact that resuscitation occurs when the patient is unconscious. In summary, the data indicate that the development of anxiety disorders depends on the strength of the stressor as well as on personal vulnerability factors.

The 11 ICD patients with anxiety disorders observed their own body more intensively to check for irregularities. They were convinced that they could reliably detect threatening signs. This finding is in line with those of Hegel et al.(53), who also reported clinically relevant anxiety in one-third of 38 ICD patients and found that the belief of ICD patients in their ability to predict ICD shocks is closely connected with anxiety. Moreover, Pauli et al. (42) demonstrated that the degree of fear of a renewed shock is closely related to the intensity of the avoidance behavior and panic-related cognitions. It is conceivable that some patients may react with anxiety after erroneously interpreting pulse changes as a danger and premonitory sign indicating a renewed shock. The connection between (usually) harmless somatic manifestations and the fearful memory of the shock in terms of a catastrophic association may be a further step in the development of an anxiety disorder in that the misinterpretation evokes anxiety, which in turn leads to a psychovegetative reaction. This can give rise to thoughts of losing control ("I’ll be lying helpless somewhere, and nobody will come to rescue me") or being vitally threatened ("I’m going to die"). This in turn enhances the anxiety and the psychovegetative reaction. Thus, the vicious circle of anxiety is set into motion as is typical for panic disorders and agoraphobia. Reiss (54) concluded that to predict panic, it is more important to know what an individual expects to happen as a result of becoming anxious than to know how frequently they experience anxiety states.

The first occurrence of panic attacks can be explained by a vulnerability-stress model (55). The vulnerability-stress model assumes that any individual can develop panic attacks under sufficient stress and that the amount of stress needed is determined by the individual’s vulnerability. Information can be gained on individual vulnerability differences by observing ICD patients because shock can be understood as a semiexperimentally defined stress likely to evoke panic attacks, which can then give rise to anxiety disorders. It would thus be possible to determine the influence of psychological, physiological, and biological traits.

There are some limitations to the present study. Multiple comparisons were made without correcting the error, and the validity and reliability of our ICD questionnaire are unknown. A Bonferroni adjustment for multiple testing in bivariate analysis of data would only have indicated a tendency toward higher shock frequency in anxiety disorders. Dysfunctional cognitions continue to differ significantly. Furthermore, the retrospective design does not disclose the time at which individuals increased their self-observation, developed a fear of renewed ICD shocks, and started living in a state of shock expectancy. A prospective study is needed to answer questions such as the following: Are fearful individuals more likely to develop anxiety disorders? Are catastrophe-linked thoughts already established before the onset of the anxiety disorder, or do they only arise during the course of the illness? Do patients who develop anxiety disorders observe their own bodies more intensively from the start?

Modern medicine can be intensive and can place patients under enormous psychological stress. Therefore, the psychological consequences of medical interventions must be seriously considered as potentially adverse reactions. It is important to develop additional psychological treatments to prevent these serious side effects.

Received for publication October 26, 1999.

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