Psychosomatics 44:222-236, June 2003
© 2003 The Academy of Psychosomatic Medicine
Predicting Panic Disorder Among Patients With Chest Pain: An Analysis of the Literature
Jeff C. Huffman, M.D., and
Mark H. Pollack, M.D.
Received May 14, 2002; revision received Sept. 18, 2002; accepted Oct. 4, 2002. From the Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School; and McLean Hospital, Belmont, Mass. Address correspondence and reprint requests to Dr. Huffman, Massachusetts General Hospital, Warren 605, Boston, MA 02114; JHuffman{at}partners.org (e-mail).
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ABSTRACT
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As many as 25% of patients with chest pain who come to hospital emergency departments have panic disorder. Rates of panic disorder are even higher among those who present for outpatient evaluation of their chest pain. Unfortunately, panic disorder remains largely undiagnosed and untreated in these settings. The authors reviewed studies published between 1970 and 2001 that addressed the prevalence of panic disorder among persons who seek treatment for chest pain in an emergency department or outpatient cardiology clinic. A meta-analysis of the findings revealed five variables that appear to correlate with higher rates of panic disorder among persons who present with chest pain: 1) absence of coronary artery disease, 2) atypical quality of chest pain, 3) female sex, 4) younger age, and 5) a high level of self-reported anxiety. Further studies of these and other variables associated with panic disorder should aid in the detection of this disabling but treatable cause of chest pain.
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INTRODUCTION
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Panic disorder affects one to four of every 100 people in the United States.1–3 Individuals with this condition experience recurrent panic attacks and persistent worry or behavior change as a result of such attacks.4 Panic disorder has pervasive effects on quality of life and at times can be profoundly disabling. Persons with panic disorder have high rates of depression and other psychiatric disorders,5–8 as well as a propensity toward medical illness.9–12 Further, persons with panic disorder have substantial functional, occupational, and financial disability as a result of their symptoms.13–18 Panic attacks are associated with multiple somatic symptoms that resemble those of common medical conditions, including palpitations, tachycardia, diaphoresis, dyspnea, a sensation of choking, chest pain or pressure, dizziness, flushing and chills, paresthesias, nausea, abdominal distress, and tremulousness.4 Because panic symptoms resemble those of medical conditions, patients with panic disorder use medical services at a much higher rate than those without panic disorder.19–21
Chest pain is one such somatic symptom that occurs commonly (22%–70%) during a panic attack;9,22 moreover, the Epidemiologic Catchment Area Study23 found that persons with chest pain were four times more likely to have panic disorder than were those without chest pain.24 Typically, individuals with panic disorder and chest pain do not initially seek treatment from a psychiatric caregiver but present for evaluation of chest pain at an emergency department or cardiology clinic. Such patients often undergo expensive cardiac workups but receive neither a diagnosis of panic disorder nor treatment for the disorder.25,26 This lack of identification and treatment of panic disorder is unfortunate, given the functional incapacity created by the disorder and the array of effective treatments available for this condition.
Several studies have examined the prevalence of panic disorder among patients with chest pain who seek treatment in a general medical setting. These studies have found high rates of panic disorder among patients with chest pain who present to emergency departments; even higher rates are seen among outpatients in cardiology clinics who undergo a diagnostic workup of their chest pain. However, few studies have sought to identify specific patient characteristics that are significantly associated with panic disorder in this population. Kushner and colleagues,27 in 1989, interviewed patients with panic disorder, chest pain, and normal coronary arteries; they determined that self-reported anxiety, female gender, and younger age were each predictive of panic disorder in this population. Similarly, two other groups of researchers have used a combination of factors (gender, age, agoraphobia and somatization rating scale scores, and a measure of pain quality) to create equations that attempt to predict panic disorder in patients who present with chest pain in emergency and cardiology departments.28,29
In this article, we review the literature identifying the prevalence of panic disorder among patients with chest pain who seek treatment in general medical settings. Further, we examine how differences between studies in methods, setting, and patient characteristics appear to affect the rates of panic disorder that are reported. Using this review, we identify five specific variables that appear to be associated with panic disorder among patients who present with chest pain in emergency departments and outpatient services. This profile may potentially facilitate the identification of panic disorder among patients with chest pain in general medical settings.
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METHOD
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Study Selection
We used a multistep search process to identify published research reports that examined the association between panic disorder and chest pain. We initially searched the PubMed (National Library of Medicine) computer database for relevant studies. This database contains MEDLINE citations along with selected other citations. We conducted a search of the PubMed database from 1970 to 2001 using the following search terms: "panic disorder and chest pain," "panic and chest pain," "panic attack and chest pain," "panic disorder and angina," and "panic and angina." We then manually reviewed articles obtained through the PubMed search to identify additional articles pertinent to the topic of this review. From these studies, we selected all original research studies that investigated the prevalence of panic disorder among patients with chest pain in outpatient settings or emergency departments.
Statistical Analysis
Throughout this article, statistical analysis of data to compare two groups (e.g., the rate of panic disorder in subjects with coronary artery disease compared to the rate of panic disorder in subjects without coronary artery disease) was completed in two ways. Both methods used chi-square analysis to determine whether statistically significant differences between the groups were present; in all cases, differences between two groups were considered statistically significant only if the analysis resulted in a p value of less than 0.05.
The first method of analysis summed the total number of patients in all studies (e.g., the total number of women in all studies versus the total number of men) and used chi-square analysis to compare panic disorder prevalence between the two summed groups. This method of analysis essentially weighted studies on the basis of the number of patients enrolled in each study.
To account for the possibility that the larger studies may have had methodological or setting-related differences that could have skewed the analysis, we performed a second analysis of the data by averaging the proportions of patients with panic disorder in each study. This second method gave equal weight to each study regardless of the number of patients in the study. Between-group differences were considered statistically significant only if both methods resulted in a p value less than 0.05.
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HISTORICAL PERSPECTIVE AND PREVALENCE IN THE EMERGENCY DEPARTMENT
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The relationship between chest pain and anxiety has long been recognized. In 1871, Da Costa30 described "irritable heart," a condition in which chest discomfort was caused by emotional upset. In 1882, Osler31 discussed the difficulty of differentiating cardiac and noncardiac etiologies of chest pain and described a subset of patients with atypical chest pain and nervousness. Since then, numerous authors have linked anxiety and chest pain and have described such symptoms by using terms such as Da Costa's syndrome, neurocirculatory asthenia, and effort syndrome.9
One of the first studies to determine that an anxiety disorder can cause chest pain was completed by Waxler and associates32 in 1971. The researchers interviewed 86 female patients with chest pain but without significant coronary obstruction as assessed with angiography. Of these, fully 40% met the criteria for "anxiety neurosis," a DSM-II33 precursor of panic disorder. Bass and Wade,34 in 1984, examined rates of anxiety neurosis in 99 male and female outpatients with chest pain who were referred for angiography. They identified anxiety neurosis in 19% of the patients, including 37% of the patients without significant obstruction as assessed with angiography. Unfortunately, these two early investigations had diagnostic and methodological shortcomings; outdated diagnostic nomenclature was used in both studies, and the method used by Waxler et al. for the diagnosis of psychiatric disorders was unclear. Still, the results suggested a significant association between chest pain and anxiety, especially in patients with normal coronary angiograms, that has led to further investigation into the association between panic disorder and chest pain.
Since these seminal studies, at least 20 published reports have examined the prevalence of panic disorder in patients with chest pain.25–29,35–51 Three major studies in emergency departments found high rates of panic disorder among patients seeking evaluation of chest pain25,26,35 (Table 1). Yingling and associates26 found that 18% of 229 patients who presented to an emergency department with chest pain met the criteria for panic disorder; the group who met the panic disorder criteria included 19% of the patients with an acute coronary syndrome. A larger study of more than 1,000 patients by Worthington and co-workers35 found that 20% of emergency department patients with chest pain met the criteria for panic disorder. A third study, by Fleet and colleagues,25 found that 25% of 441 patients who presented to an ambulatory emergency department in a cardiac hospital met the criteria for panic disorder. The higher prevalence of panic disorder in this final study may be explained by the ambulatory nature of the emergency department. Patients with severe chest pain or a history of cardiac disease may have been more likely to call 911 and arrive for care by ambulance rather than by self-presenting to an ambulatory emergency department. In addition, this study occurred in a specific setting—a cardiac emergency room in a cardiac hospital—that differed from the general hospital settings of other two studies. These studies are notable for having few exclusion criteria; essentially all consenting, communicative patients were enrolled without regard to prior cardiac disease. In short, it appears that roughly one in five patients presenting to an emergency department with chest pain has panic disorder.
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TABLE 1. Studies of the Prevalence of Panic Disorder Among Patients Presenting to Emergency Departments With Chest Pain
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Other studies of panic disorder in patients with chest pain have examined more selected patient populations, usually outpatients undergoing diagnostic evaluation for chest pain. These studies, and their results, allow for an examination of the factors that may increase the likelihood of panic disorder in a given patient with chest pain.
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FACTORS INCREASING THE LIKELIHOOD OF PANIC DISORDER
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Absence of Coronary Artery Disease
Seven studies of panic disorder have examined inpatients and outpatients referred for diagnostic evaluation of chest pain (Table 2 and Table 2 (continued)).29,36–39,43,51 The studies generally found that 20%–38% of the patients had panic disorder.29,36,37,43,51 However, the results of two studies significantly deviated from the others. A study by Carney and associates38 of 100 outpatients undergoing coronary angiography found that only 5% had panic disorder but 28% had major depression. This rate of depression is substantially higher than that observed in most studies of psychiatric comorbidity with chest pain. In contrast, Carter and colleagues39 found a 56% rate of panic disorder among 50 outpatients referred for myocardial scintigraphy. The reasons for the deviations in these two studies are not clear, as their patient populations, exclusion criteria, and methods appear similar to those of the other studies. What is clear is that the rate of panic disorder among patients referred for outpatient diagnostic evaluation of chest pain appears to be at least as high as the rate in patients presenting to an emergency department with chest pain.
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TABLE 2. Studies of the Prevalence of Panic Disorder Among Chest Pain Patients With and Without Coronary Artery Disease
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Furthermore, the absence of coronary artery disease appears to predict a greater likelihood of panic disorder in patients presenting with chest pain. In all seven studies, the rate of panic disorder in patients with normal or near-normal diagnostic studies was significantly greater than the rate in patients who received a diagnosis of coronary artery disease. When the results of these seven studies were summed, the rate of current panic disorder in patients without coronary artery disease was 42% (169 of 400), compared to 8% (21 of 251) in patients with a positive diagnostic test for coronary artery disease ( 2=60.2, df=1, p<0.0001). We performed a second analysis of the data by summing the proportions of patients with panic disorder (see Method section for more detail). This second method of analysis also revealed a significantly higher rate of panic disorder in patients without coronary artery disease (44% for patients without coronary artery disease, compared with 10% for patients with coronary artery disease) (2=58.8, df=1, p<0.0001).
While the seven studies just discussed evaluated both patients with and patients without coronary artery disease, three other studies focused on patients with chest pain and normal coronary angiography (i.e., outpatients without coronary artery disease) (Table 3).40–42 These studies found that approximately one-third of such patients had panic disorder, a similar but slightly lower rate of panic disorder than was found among the patients without coronary artery disease in the seven previously discussed studies. The slightly lower rate of panic disorder in these three studies may be related to the use of more stringent criteria for panic disorder. In these studies, panic disorder was diagnosed only if the patient had at least one panic attack weekly in the 3 weeks before evaluation, in addition to meeting the usual DSM-IV criteria for panic disorder.
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TABLE 3. Studies of the Prevalence of Panic Disorder Among Cardiology Outpatients Without Coronary Artery Disease
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Therefore, a negative diagnostic finding for cardiac disease in a patient with chest pain is associated with a higher likelihood of panic disorder. Still, it is notable that patients with chest pain whose diagnostic tests indicated the presence of cardiac disease had a rate of panic disorder that was roughly four times the rate for the general population, suggesting substantial co-occurrence of panic disorder and coronary artery disease.
Younger Age
The relationship between age and prevalence of panic disorder has been examined in multiple studies and in a variety of settings. Eleven studies examined age as an independent variable in the diagnosis of panic disorder in patients with chest pain.25,27,29,39,40,42,43,45,47,48,51 Of these 11 studies, six25,27,40,42,43,51 found a statistically significant association between younger age and the diagnosis of panic disorder. The lack of a significant association in the other five studies may be partly explained by the small number of patients in those studies; four of the five studies with more than 100 patients found a significant association between younger age and panic disorder.
Eight of the 11 studies examining the association between age and panic disorder reported mean ages for patients with and without panic disorder.25,27,39,40,42,43,45,51 When the results of these eight studies were combined, a significant association between younger age and the presence of panic disorder was revealed (Table 4). When the results of these studies were summed by using an average that was weighted by the number of patients in the studies, patients with panic disorder had a mean age of 45.0 years, compared with a mean age of 54.7 years for those without panic disorder (2=535, df=1, p<0.0001). Although it is difficult to combine the results of different studies with divergent methods and settings, patients with panic disorder were an average of more than 4 years younger than those without panic disorder in each of the eight studies, suggesting a consistent trend regardless of setting or methods. Furthermore, we reanalyzed the data to weight equally each study regardless of the number of patients; this reanalysis also found a statistically significant correlation between younger age and panic disorder (mean=45.9 years for patients with panic disorder; mean=54.9 years for those without panic disorder) (2=373, df=1, p<0.0001).
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TABLE 4. Studies Examining Effects of Gender and Age on the Prevalence of Panic Disorder Among Chest Pain Patients
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Female Sex
In the general population, panic disorder occurs two to three times more frequently in women than in men.4 It would therefore seem likely that a greater proportion of women would have panic disorder in the specific population of chest pain patients, as well. Eleven studies25,29,36,39,40,42,43,45,47,48,51 described rates of panic disorder in patients with chest pain and examined the potential association between female gender and elevated panic disorder prevalence. Only two of these studies40,51 found statistically significant associations between female gender and panic disorder. Although it is possible that gender is not significantly related to the prevalence of panic disorder in patients with chest pain, the studies simply may not have had enough subjects to reveal such a difference. Of the eight studies that reported panic disorder rates quantitatively by gender, seven found that panic disorder was more common in women,25,27,39,40,43,45,51 with the eighth42 finding nearly the same rate in men and women (among 94 patients with chest pain, 35.1% of men and 33.3% of women had panic disorder) (Table 4). These findings suggest a substantial trend toward association between female sex and panic disorder among patients with chest pain.
Furthermore, the combined results of the same eight studies that reported gender differences quantitatively suggested a significant association between female gender and panic disorder among chest pain patients (Table 4). In these studies, 44% (261 of 593) of women met the criteria for panic disorder, compared to 30.5% (200 of 655) of men, a statistically significant difference (2=15.35, df=1, p<0.0001). This statistical association again held when the data were reanalyzed to provide equal weight to each study (a 46.4% rate of panic disorder in women versus 37.4% in men) (2=6.05, df=1, p<0.02).
Atypical Chest Pain
Atypical chest pain appears to be a predictive indicator of panic disorder among patients who present with chest pain. In most studies, typical chest pain was defined as pain that is substernal in location, initiated by exertion, and relieved by rest or nitroglycerin.27,44,45 In most studies of chest pain and panic disorder, atypical chest pain has been defined as chest pain that met only one or two of the three criteria for typical chest pain.
Five papers27,45–48 have examined the prevalence of panic disorder among patients with atypical chest pain (Table 5). The prevalence of panic disorder in these studies ranged from 16% to 57%. When the results of the five studies were summed, 46% (223 of 486) of patients with atypical chest pain had panic disorder, a substantially higher rate than that found in studies that included patients with typical chest pain. Even the study by Wulsin and associates,47 which reported the lowest panic disorder prevalence (16%), found that another 43% of patients had panic attacks without meeting the full panic disorder criteria; thus 59% of patients with atypical chest pain in this study had panic attacks.
The variability in panic disorder prevalence among studies of patients with atypical chest pain may be explained partly by differences in methods. The two studies of atypical chest pain by Wulsin and colleagues46,47 found lower rates of panic disorder (16%–31%) than were found in other studies of atypical chest pain. These two studies used a different, and less precise, definition of atypical chest pain, "all pains which did not meet typical description of angina." Further, these studies evaluated patients whose chest pain had a high likelihood of being atypical, rather than applying strict criteria to determine the nature of chest pain. Hence, these studies potentially included patients with typical chest pain. The use of less stringent guidelines for exclusion of patients and a less precise definition of atypical chest pain may have contributed to the lower reported prevalence of panic disorder.
Finally, atypical chest pain is also associated with increased rates of panic disorder in patients with established coronary artery disease. Basha and associates44 studied 49 patients with coronary artery disease and chest pain and found that 41% of the patients with atypical chest pain met the criteria for panic disorder, compared to none of the patients with typical chest pain (p<0.001). This finding suggests that, although patients with coronary artery disease may have lower rates of panic disorder than those without coronary artery disease, atypical chest pain in either population is associated with high rates of panic disorder.
High Level of Self-Reported Anxiety
Not surprisingly, patients with chest pain who had a high level of self-reported anxiety appeared to have elevated rates of panic disorder. Two studies evaluated patients with high anxiety scores on the Hospital Anxiety and Depression Scale, a self-report questionnaire (Table 6).49,50 Chignon and colleagues49 evaluated 50 patients referred for ambulatory ECG monitoring who had elevated Hospital Anxiety and Depression Scale anxiety scores and found that 62% met the criteria for panic disorder. Kuijpers and co-workers50 studied 59 patients who presented to an emergency department with chest pain or palpitations, who had elevated anxiety scores on the Hospital Anxiety and Depression Scale, and who were discharged home; fully 75% of these patients met the criteria for panic disorder.
It should be noted that both studies evaluated patients who were likely to have low rates of coronary artery disease and high rates of atypical chest pain. The first study evaluated patients generally considered to be at low risk for coronary artery disease, as patients referred for outpatient ECG monitoring generally are considered to have lower risk of coronary artery disease than those who undergo coronary angiography. The second study evaluated patients in an emergency department who were found to have no cardiac origin for their chest pain or palpitations and who were then discharged (suggesting low rates of coronary artery disease and possibly high rates of atypical chest pain, since the patients were not admitted). Hence, these factors may have contributed to the elevated rates of panic disorder found in the two studies. However, the substantial rates of panic disorder in both studies—higher than in any other study of chest pain and panic disorder—suggest that self-reported anxiety may be an independent predictor of panic disorder in patients with chest pain. Future studies comparing rates of panic disorder in patients with normal and elevated levels of self-reported anxiety will help to delineate the extent to which elevated anxiety scores may predict panic disorder.
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DETECTION MODELS FOR PANIC DISORDER
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Three groups have attempted to prospectively predict the presence or absence of panic disorder among patients with chest pain. Kushner and colleagues27 used discriminant function analysis to create a detection model predicting panic disorder in a group of patients with atypical chest pain. This model, which included self-reported anxiety, age, and gender, accurately predicted the presence or absence of panic disorder in 76% of the patients in the study. Thus these three variables in combination appear to aid in the prediction of panic disorder, at least for patients with atypical chest pain.
Fleet and associates28 created a similar equation by logistic regression analysis; they used gender, agoraphobia symptoms, and the quality/location of chest pain as predictive variables in a study of patients presenting with chest pain to an emergency department. Using this equation, they were able to predict accurately the presence or absence of panic disorder in 84% of the patients. The greater success of this model may have been related to the inclusion of the agoraphobia scale score in the equation. Agoraphobia, an anxiety disorder in which one is apprehensive about being in situations from which escape may not be possible or in which help may not be available, is typically comorbid with panic disorder. Hence, it may be difficult to claim that agoraphobia is an independent predictor of panic disorder. However, given the substantial co-occurrence of agoraphobia and panic disorder, a rapidly administered agoraphobia scale would be useful in the diagnosis of panic disorder.
Dammen and co-workers51 also used logistic regression analysis to create a panic disorder detection model in a study of cardiology outpatients. This model included age, a measure of the quality and location of the chest pain, score on an agoraphobia scale, and scores on somatization scales to predict panic disorder. Using this model, the authors accurately predicted the presence or absence of panic disorder in 78% of the subjects. The authors also used a three-item screening survey to predict panic disorder. The survey consisted of questions asking patients whether they felt they were going to pass out, whether they experienced the chest pain as exhausting or tiring, and the extent to which they had been bothered by the pain in the last 7 days. The authors found that this brief survey accurately predicted panic disorder in 74% of the subjects. Finally, in two studies,27,38 the results of a self-administered anxiety scale, the Zung Anxiety Scale, were used to correctly classify 70%–73% of chest pain patients with or without panic disorder.
In summary, five variables appear to be associated with a greater likelihood of panic disorder among patients presenting with chest pain. Three of those variables—absence of coronary artery disease, female gender, and younger age—have been associated significantly with greater rates of panic disorder among chest pain patients in several studies. The two remaining variables—atypical chest pain and self-reported anxiety—also appear to be associated with higher rates of panic disorder, although not enough studies have been completed to determine the statistical significance of these associations. Using subsets of these five variables, researchers have been able to predict panic disorder among chest pain patients with relative accuracy. Yet-to-be-developed predictive models that use all five of these variables may well predict panic disorder even more accurately.
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CLINICAL IMPLICATIONS
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As noted throughout this article, high rates of panic disorder are present among patients who present to general medical settings with chest pain. In addition, panic disorder is associated with substantial functional morbidity13–18 and elevated use of medical services.19–21 Given these findings, clinicians in the general medical setting must have an effective plan for evaluation and treatment of panic disorder.
Evaluation of chest pain patients for panic disorder in general medical settings should be both rapid and effective. Wulsin and associates52 recently completed a study in an emergency department that used simple screening instruments to identify patients with panic disorder. They evaluated a group of 156 chest pain patients who had been transferred to an area of the emergency department that treats stable, low-risk patients with normal or nondiagnostic ECGs. To identify patients with panic disorder, they used the Panic Syndrome Checklist,53 a self-report questionnaire consisting of five yes-or-no questions. Patients with a positive screen on the Panic Syndrome Checklist were then interviewed by clinicians using the panic disorder module of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID).54 Research psychiatrists and emergency room clinicians both used the SCID to interview patients; the researchers and the clinicians agreed on the presence or absence of panic disorder in 79% of the cases. The results suggest that a short self-report questionnaire can be used in a general medical setting to identify patients who are likely to have panic disorder and that a structured interview by a general medical physician can be used to verify the presence of panic disorder with reasonably good accuracy.
On the basis of the data from our meta-analysis, we recommend that patients with any two of the following characteristics be screened for panic disorder: 1) atypical chest pain, 2) absence of coronary artery disease (as demonstrated by a normal coronary angiogram or exercise stress test), 3) female gender, or 4) age below 50 years. Patients with these characteristics could be given a self-report questionnaire based on the Panic Syndrome Checklist (Appendix 1). Patients who screen positive for panic disorder on the Panic Syndrome Checklist could then be referred for psychiatric consultation (if readily available) or be screened for panic disorder by the general medical physician using the DSM-IV criteria for panic disorder.
Once the diagnosis of panic disorder is established, treatment can be initiated. Both selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are effective in the treatment of panic disorder.55,56 Benzodiazepines act more rapidly to reduce symptoms, although SSRIs are better choices for patients who have a history of substance abuse or comorbid psychiatric illnesses such as major depression, generalized anxiety disorder, or social phobia. Patients can be released from the emergency department or outpatient medical setting with a prescription for a benzodiazepine (e.g., 0.5 mg of clonazepam at night for 3 days, increased to 0.5 mg twice a day thereafter) or an SSRI (e.g., 10 mg/day of paroxetine, citalopram, or fluoxetine for 3 days, increased to 20 mg/day thereafter). In addition, follow-up with a psychiatrist (if readily available) or the patient's primary care physician should be arranged within 1–2 weeks to monitor symptoms and to manage the medication dose and side effects.
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CONCLUSIONS
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Approximately 20% of all patients who present to emergency departments with chest pain meet the criteria for panic disorder. Rates of panic disorder are at least that high among patients who present to outpatient cardiology clinics for diagnostic evaluation of chest pain. These high rates of panic disorder among chest pain patients have been well described, yet few studies have attempted to determine the characteristics of the patients who meet the criteria for a panic disorder diagnosis.
In this article, we reviewed the literature describing rates of panic disorder among patients with chest pain. Our analysis of this literature revealed a number of variables associated with a greater prevalence of panic disorder in such patients. Statistically significant associations with panic disorder have been found for absence of coronary artery disease, female gender, and younger age. Further, on the basis of prevalence studies and detection models, atypical quality of chest pain and an elevated level of self-reported anxiety also appear to be positively associated with panic disorder, although further studies of these associations are necessary. Detection models that use these and other variables have shown relative accuracy in predicting panic disorder in this population.
As with the results of any analysis using data from various studies and different patient populations, our statistical conclusions are limited by the inability to account for differences among studies in methods or selection of patients. Reporting bias may also have affected our data collection and conclusions. Specifically, studies that failed to find significant associations may be less likely to be reported, potentially skewing our findings toward a significant association between these variables and panic disorder. However, the trends in age, sex, and coronary artery disease status noted in the overall analysis were also present in virtually all of the individual articles examined, regardless of the methods or population. In addition, the statistically significant associations between age, sex, coronary artery disease status, and panic disorder were seen consistently both in our analyses using weighted averages and in those that gave all studies equal weight.
The cohort of patients with coexisting panic disorder and coronary artery disease requires further study. As noted earlier in this article, rates of panic disorder appear to be approximately four times greater in patients with coronary artery disease than in the general population. However, there has been less study of panic disorder prevalence among persons with coronary artery disease than among persons without coronary artery disease or those with atypical or nonanginal chest pain. Further study is needed to confirm the elevated rates of panic disorder among patients with coronary artery disease. In addition, the comorbidity of panic disorder and coronary artery disease can be very difficult for psychiatrists and cardiologists to treat, because chest pain in patients with this comorbidity may be due to an acute coronary syndrome, a panic attack, or both. Studies that delineate methods of distinguishing panic attacks from true coronary events in this population would be clinically useful.
It is important to note that evaluation of panic disorder should not preclude a careful evaluation for more acute general medical causes of chest pain. Many patients with coronary artery disease have atypical presentations of myocardial infarction. This is especially true among women57—the very population with higher rates of panic disorder. Clinicians who evaluate patients with chest pain should carefully consider both acute medical causes and panic disorder as potential etiologies of the symptom.
Panic disorder is not the only psychiatric illness associated with chest pain. Generalized anxiety disorder also appears to be associated both with unexplained chest pain and with presentation to medical settings for evaluation of chest pain.58–61 At least one study of patients with chest pain and normal coronary arteries found that the rate of generalized anxiety disorder in this group was equal to the rate of panic disorder.62 In addition, depression38,46,63 and somatization disorder64 also have been associated with elevated rates of chest pain.
Furthermore, patients with panic disorder have high rates of comorbid psychiatric illness;5–8 this is true for both the general population of panic disorder patients and for those with panic disorder who present to medical settings with chest pain. Fleet and colleagues65 studied 108 patients with panic disorder who presented to an emergency department with chest pain. They found that these patients had elevated rates of comorbid generalized anxiety disorder (33%), major depression (11%), and obsessive-compulsive disorder (3%). In addition, these elevated rates of comorbid psychiatric illness did not differ significantly from the rates of comorbidity seen in a population of panic disorder patients who were treated in a psychiatric clinic.
Each year, as many as 1 million patients with panic disorder present to emergency departments with chest pain, and panic disorder remains undiagnosed in more than 94% of such patients.25,26 These findings are particularly troubling given the profoundly disabling—and treatable—nature of panic disorder. In addition, as a result of their chest pain, patients with panic disorder are frequently seen in inpatient medical and outpatient cardiology settings. The identification of factors associated with panic disorder may facilitate diagnosis and treatment of such patients in these settings. In this study we have identified five such factors. Further study is necessary both to define other variables associated with higher rates of panic disorder in chest pain patients and to develop accurate screening tools to facilitate diagnosis. By understanding the prominent characteristics of patients with panic disorder who present to general medical settings with chest pain, physicians will be more readily able to make a diagnosis for such patients and initiate treatment.
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ACKNOWLEDGMENTS
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The authors thank Theodore A. Stern, M.D., for editorial assistance.
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ABSTRACT
INTRODUCTION