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Panic Disorder: Diagnosis and Treatment in Emergency Medicine
CONCEPTS
Panic Disorder: Diagnosis and Treatment in Emergency Medicine
Receivedfor publicationJuly 17, 1995, Revisions receivedNovember 18, 1995; September 3, 1996; and January 31, 1997. Acceptedfor publication February 3, 1997.
Panic disorder is a newly recognized psychiatric illness involving unexpected, unprovoked attacks of anxiety. Patients with panic disorder commonly seek treatment in the ED, It is important for the emergency physician to properly recognize and categorize this disorder to initiate appropriate treatment, Illness description and treatment guidelines of this disorder are discussed in this article.
Copyright © by the American College of Emergency Physicians.
[Zun LS: Panic disorder: Diagnosis and treatment in emergency medicine. Ann EmergMed July 1997;30:92-96.]
From the Department of Emergency Medicine, Mount Sinai Hospital Medical Center, Chicago, IL.
Leslie S Zun, MD, MBA
INTRODUCTION Panic disorder is a syndrome characterized by unexpected and unprovoked attacks of anxiety that produce both cognitive and physical symptoms. 1 It is the most common anxiety disorder. 2 In the past, many individuals with panic disorder were considered to have generalized anxiety disorder. Patients with panic disorder are commonly seen m the ED. However, the diagnosis is rarely made there. When panic disorder is misdiagnosed, unnecessary tests, inappropriate treatment, and incorrect referrals may result. Emergency physicians should become familiar with the diagnosis and treatment of this newly defined disorder. In this article the clinical presentation, causes, natural history, associations, and treatment of panic disorder are discussed.
EPIDEMIOLOGY The lifetime prevalence of panic disorder in the general population is 1.6%. 3 The disorder has a unimodal distribution, peaking in the third decade of life. Panic disorder affects more females than males. 3,4 It is rarely found in older patients. 4 In the single study of the prevalence of panic disorder treated in the ED, Ross et al 5 found that 4% of all patients presented with psychiatric illness. Of these, 27% had panic disorder. In another study, patients with known, panic disorder were found to be frequent users of EDs. Their rate of
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ED use was higher than that of patients with major depression and other psychiatric illnesses. 6 The incidence of panic disorder is similar among whites, blacks, and other racial groups. 4,r However, blacks with this disorder have been reported to have a higher rate of ED visits than whites with panic disorder/It is not known whether the incidence is different in the Hispanic population. However, the disorder termed ataque de nervious (attack of the nerves) has a significant overlap with panic disorder in the Latin American population. 8 PRESENTATION
Panic disorder is common in the general population; therefore patients with this disorder frequently present to the ED. Early recognition facilitates appropriate workup and proper treatment. The major distinguishing feature of panic disorder is the combination of cognitive and physical symptoms. Onset is rapid, peaking within 10 minutes, and the attack lasts about 60 minutes (Figure). The typical patient has two to four attacks per week, often accompanied by anticipatory anxiety.
Figure.
Table.
Differential diagnosis of panic disorder. Panic DisorderSymptom
A patient who sustains four panic attacks in 4 weeks or one or more attacks followed by 4 weeks of continuous anticipatory anxiety may be said to have panic disorder. 1 Panic disorder has several symptoms that are referable to various body systems: chest pain, shortness of breath, palpitations, dizziness, abdominal pain, and nervousness. Patients may have the same symptom complex during each panic attack, or they may display a changing symptom complex. The symptom complex provides a long list of differential diagnoses, including adrenergic excess (Table). Panic disorder was diagnosed in 33% to 59% of patients who presented with chest pain, in 25% to 50% of those who presented with vestibular symptoms, and in 33% who presented with gastrointestinal complaints. 9 Any of the following types of patients may seek treatment in the ED: (1) those with undiagnosed panic disorder who present with a symptom combination consistent with a panic attack, (2) those with known panic disorder who present with their usual symptom combination, and (3) those with known panic disorder who present with an unusual symptom combination. The approach to each of these types of patients varies.
Possible Medical Cause
Chest pain
Angina Myocardial infarction Costochondritis Pleuritis/pneumonia Shortness of breath Hyperventilation Pulmonary embolism Congestive heart failure Chronic obstructive pulmonary disease Palpitations Paroxysmal atrial tachycardia Supraventricular tachycardia Mitral valve prolapse Ventticular paroxysmal contractions Atrial paroxysmal contractions Hyperthyroidism Hypoglycemia Pheochromocytoma Dizziness Orthostatic hypertension Acute anemia Benign positional vertigo Meniere's disease Acute labyrinthitis Numbness Hyperventilation Nervousness Hyperthyroidism Hypoglycemia Modifiedwith permissionfrom McGlynnTJ, Metcalf IlL (eds):Diagnosisand Treatmentof Anxiety Disorders.'A Physician'sHandbook. Copyright© by the AmericanPsychiatric Association,1990.
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Diagnostic criteria for panic disorder. At some time during the disturbance, one or more panic attacks occurred that were unexpected and were ROttriggered by situations in which the person was the focus of attention. Four attacks have occurred during a 4-week period, or one or more attacks have been followed by a period of at least 1 month of persistent fear of having another attack. At least four of the following symptoms occurred during at least one of the attacks: Shortness of breath (dyspnea) or a smothering sensation Dizziness, unsteady feeling, or fainting Palpitations or accelerated heart rate (tachycardia) Trembling or shaking Sweating Choking Nausea or abdominal distress Depersonalization (the feeling that one's body is unreal) or derealization (the feeling that reality is altered) Numbness or tingling sensations (paresthesia) Flushes (hot flashes) or chills Chest pain or discomfort Fear of dying Fear of going crazy or of doing something uncontrolled In one of the attacks, at least four of the symptoms developed suddenly and increased in intensity within 10 minutes of the beginning of the first symptom noticed in the attack. No organic factor (eg, amphetamine or caffeine intoxication, hyperthyroidism} started or maintained the disturbance. Modifiedwith permissionfrom PanicDisorder" Diagnosis, Treatmentand Managemen~ 1990:35-36.Copyright© by the AmericanPsychiatricAssociation.
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PANIC DISORDER ,Zu~.
For patients with undiagnosed panic disorder who present with a symptom combination consistent with a panic attack (diagnostic category 1), the clues to the diagnosis of panic disorder include the patient's age, typical physical and psychologic symptoms, the time it takes the attack to complete its course, and lack of other identifiable causes. These patients need an appropriate evaluation to determine whether an underlying cause for their panic attacks exists. The differential diagnosis is extensive (Table) and includes adrenergic excess. Frequently the diagnosis is made on the basis of exclusion of other possible causes. A patient known to have panic disorder who presents to the ED with the same symptom combination he or she has experienced previously or with a similar one (diagnostic category 2) is most likely having another panic attack. In this instance, it is rare for the patient to require an extensive workup. It is imperative for the emergency physician to recognize that the disorder is psychologic and not to reinforce the patient's belief that something is physically wrong. For patients with known panic disorder who present with a symptom combination that meets the criteria for panic disorder but is different from one exhibited during their usual panic attack (diagnostic category 3), an adequate history and physical examination may be useful in determining that this presentation is another form of a panic attack. Such a diagnosis is easier to make if the presenting attack fits the time course and symptom complex found with panic attacks. If not, a more extensive workup may be necessary if the emergency physician is concerned about possible life- or limb-threatening causes. CAUSES OF PANIC DISORDER
The cause of panic disorder is uncertain. It is believed to be the product of psychologic, behavioral, and biologic forces and is aggravated by stress and conflict. The disease is genetically influenced and has strong biologic correlates. 1< t 1 These correlates originate in the locus caeruleus, [3-aminobutyric acid (GABA) system/benzodiazepine receptor complex, septohippocampal region, and ventromedullary center. The locus caeruleus contains 50% of all noradrenergic receptors in the central nervous system. Stimulation of this area produces sympathetic arousal and an outpouring of catecholamine, possibly leading to panic symptoms.11,12 GABA is a neurotransmitter that decreases neuron excitability. By opening up ion channels in neurons, GABAcauses neuronal hyperpolarization and a decrease in anxiety. Benzodiazepines enhance the action of GABA, producing a calming effect. GABAantagonist can produce the opposite effect. 13
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The septohippocampal region is believed to moderate input from external and internal environments. An input mismatch causes inhibiting behavior. 14 a patient with panic disorder may have a hypersensitivity in this region. Positron emission tomography studies of panic disorder patients revealed a mismatch between the right and left parahippocampal regions not found in patients without this disorder. ~5 The ventromedullary center lacks a significant bloodbrain barrier. It responds to Pco2, pH, and acetate levels in the blood, causing central nervous system arousal. Panic disorder patients have greater sensitivity to carbon dioxide and lactate levels than persons without the disorder. 16 NATURAL HISTORY
The course of panic disorder varies. Patients may progress through six stages. Chronicity is commonly found in this disorder, 17 although 15% of patients may have complete remission. 18 Some patients may stay in one stage, whereas others may progress rapidly through all six stages. Half of the patients present m stage 1, limited-symptom attack. These patients display fewer than the four symptoms necessary for diagnosis of panic disorder. The other 50% of patients present in stage 2, panic attacks. Patients in stage 2 meet the definition of panic disorders with the appropriate frequency, duration, and four or more of the symptoms (Figure). It is believed that if the diagnosis is made in stage 1 or 2 and the patient is properly treated, the disorder is less likely to progress, is Stage 3 is hypochondnasis. A patient m this stage becomes preoccupied with concerns about medical illness, despite medical assurances. The panic attacks may become associated with environmental stimuli. This is known as phobic avoidance behavior. Driving and going to stores or shopping malls are the most frequent fears. 19 Phobic avoidance progresses to stage 4, agoraphobia 0iterally, "fear of the marketplace," or fear of where people assemble). Lelliott et al 2° found that m 23% of cases, agoraphobia was preceded by phobic avoidance. In 32% of cases, agoraphobia developed a few days after the first panic attack. In 41% of cases, agoraphobia developed after more than one panic attack and was present 1 week to 1i years tater. 2° As the disease progresses to stage 5, extensive phobic avoidance, these types of phobic behaviors develop. Stage 5 patients may become housebound. Stage 6, secondary depression, is believed to result from progressive disability and demoralization. Other authors have classified panic disorder differently. Weinstock 2 t classifies panic disorder into spontaneous
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i
attacks, situational attacks, panic attacks during sleep, and panic attacks with and without agoraphobia. ASSOCIATIONS
Panic disorder is associated with several other disorders, including sleep and eating disturbances, hyperventilation, alcoholism and substance abuse, suicide, mitral valve prolapse, and cardiovascular disease. It is also closely associated with depression, obsessive-compulsive disorder, and generalized anxiety disorder. Patients tend to fear the activities they are engaged in when a panic attack occurs. In other words, sleeping or eatmg disturbances may evolve in patients who have panic attacks while eating or sleeping. Acute and chronic hyperventilation is related to panic disorder. Although the exact relationship is obscure, hyperventilation causes panic attacks in some patients. 19 When a hyperventilating patient with panic disorder breathes into a paper bag, the CO 2 level is increased. This increase can precipitate a panic attack. Instead, the patient should be coached to reduce breathing to l0 breaths per minute.19 Panic disorder patients tend to self-medicate with alcohol and other substances to reduce the number of panic attacks. 22 These patients have a higher rate of alcohol and substance abuse than patients with other psychiatric illnesses. 6 Cocaine intoxication and withdrawal, marijuana use, and alcohol and opiate withdrawal may worsen panic disorder. 19 Suicidal ideation and suicide attempts are frequent in panic disorder patients. Cox et a123 found that 37% of patients with panic disorder had had suicidal ideation in the preceding year and that 18% had a lifetime incidence of suicide attempts. Suicidal ideation is associated commonly with secondary depression. TREATMENT
Treatment of panic disorder includes patient education, behavioral therapy, and pharmacologic therapy. Psychotherapy has not proven effective in the treatment of this disorder. 24 With the proper treatment, more than 85% of patients can become symptom free. 9 The patient must understand the illness to be reassured that the symptom pattern is characteristic of the disorder. The patient also nmst understand that with proper treatment, the panic attacks can be controlled. The National Institute of Mental Health has a hotline (800-64-PANIC) for panic disorder patients and their families. Pharmacologic treatment includes benzodiazepines, tricyclic antidepressants, and monoamine oxidase inhibitors.
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Alprazolam, a benzodiazepine, is commonly used.l,19,25-29 This drug is usually started at low doses (.25 rag, three times a day), but doses of 4 rag/day or more may be required. 26 Tricyclic antidepressants imipramine and desipramine are effective in the treatment of panic disorder. Newer antidepressants such as fluoxetine, clominparamine, and paroxetine have also been found to be effective, x7,3° Buspirone hydrochloride and [~-blockers have not been found to be effective. Behavioral therapy is useful for patients in the phobic avoidance stages. Once the patient is symptom-free for several weeks after pharmacologic treatment, the physician should encourage the patient to face the phobic stimuli. W'hen the phobias are long-standing and severe, more formal behavior therapy is necessa U. In the only study of panic disorder treated in the KD, Swinson et aP 1 enrolled patients from the ED in one of two treatment arms. Patients received reassurance or exposure instructions about confronting the situation in which the attack occurred. Although medications were not used in this study, the authors found that early intervention and exposure instructions reduced long-term consequences of panic attacks. Reassurance was not found to be as effective. Treatment of panic disorder depends on the patient's diagnostic category Patients in diagnostic category i should be reterred to a primary care physician or psychiatrist familiar with panic disorder. A short course of a benzodiazepine may be prescribed. For patients in diagnostic category 2, it is imperative for the emergency physician to recognize the disorder and to not reinforce the patient's belief that something is physically wrong. The emergency physician should explain to the patient that the panic disorder is causing the symptoms. These patients should be referred back to their treating psychiatrist or primary care physician. After a proper workup to verify panic attacks as the cause of the patients' complaints in category 3, the emergency physician should consult the primary care physician or psychiatrist to determine whether a dosage increase of the patient's psychoactive medication is warranted. COMPLICATIONS
Panic disorder is frequently misdiagnosed in general practice. Kahn 9 commented on a large study in which 70% of the patients with panic disorders had seen more than 10 consultants before the correct diagnosis was made. In another study, the most frequent consultations were from cardiology, neurology, and gastroenterology. 3x Misdiagnosis of panic disorder in the ED is costly. This issue is of particular importance in diagnostic categories 2
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I
and 3. The ED diagnosis of category 2 is frequently made without difficulty. Therefore limited testing or no testing is warranted. However, the patients in categories 1 and 3 present more of a diagnostic challenge. For patients m category 1, an initial workup must be performed to rule out organic causes. For patients in category 3, testing may be indicated, depending on clinical judgment. Inappropriate tests are often ordered for patients with panic disorder. Of patients seeking treatment in an immediate care center, laboratory testing was performed in 43% of cases. 5 Electrocardiography, CBC, and assays of blood urea nitrogen, electrolyte, and glucose level concentrations are the most commonly performed laboratory tests. 5 It should be noted that Swinson et al 3~ did not differentiate the patients into diagnostic categories. Patients with panic disorder are frequently referred to medical clinics instead of psychiatric clinics. A study of patients referred to a cardiology clinic revealed that 28% had panic disorder. 33 In another study of patients undergoing angiography for anginalike chest pain, the authors found that in 33%, the pain was a result of panic disorderY Not only is panic disorder misdiagnosed in the ED, the correct treatment is rarely prescribed in the ED. In the study by Ross etal, 5 14% of patients with panic disorder received anxiolytics, and none was referred to a psychiatrist.
8. Liebowitz MR, Slaman E, Jasine CM, et al: Ataque de nervieas and panic disorder. Am J Psychiatry 1994;151:871-875. 9. Khan B: Panic disorder. West J Marl 1991;155:517-518, 10. Torgersen S: Genetic factors in anxiety disorders. Arch Gen Psychiatry1983;40:1085-1089. 11. Redmond DE Jr, HuangYH, Snyder DR, et ah Behavioral effect of stimulation ef the nucteus locus coeruleus in the stump tailed monkey Macaca arctoidas. Brain Res 1976;116:502-51O. 12. CharneyDS, Woods SW, Nagy LM, at. al: Noradrenergic function in panic disorder. J Clin Psychiatry 1996;51(aupplA):5-11. 13. Insal TR, Ninan, PT, Aloy J, et al: A benzodiazepinereceptor mediated medal of anxiety: Studies in non-human primates and clinical implications. Arch Gen Psychiatry1984;41:741-750. 14. Gray JA: The Neuropsychologyof Anxiaty: An Inquiry Into the Functionsof the Septohippocampal System. Oxford: Oxford University Press, 1982. 15. Raiman EM. Raichle ME, Butler FK, et aL: A focal brain abnormality in panic disorder. Nature 1984;310:683-885, 16. Carr OB, Sheehan DV: Panic anxiety: A new biological disorder. J Clin Psychiatry 1984;45:323-330. 17. Pollack MH, Otto MW, RosenhaarnJF, etal: Longitudinal coarse of panic disorder: Findings from the Massachusetts General Hospital Naturalistic Study. J Clin Psychiatry1990;51:(suppl A):12-16. 18. Noyes R Jr, Ciancy J, Hoenk PR, et al: The prognosis of anxiety neurosis. Arch Gen Psychiatry 1988;37:173-178. 19. Uhde TW, Nemiah JO: Anxiety disorders, in Kaplan HI, Sadech DJ (eds): Comprehensive Textbookof Psychiatry, ed 5. Baltimore: Williams & Wilkins, 1989. 28. Lelliott P, Marks I, McNamee G, et al: Onset of panic disorder with agoraphobia: Toward an integrated mode. Arch Gen Psychiatry1989;46:1000-1084. 21. Weinsteck RS: Panic disorder. Am FaroPhysician1995;52:2055-2063. 22. Bibb JL, ChambersDL: Alcohol use and abuse among diagnosed agoraphobics. BehavRes Thor 1986;24:49-68. 23. Cox BJ, Oirenfeld DM, Swinson RP, et al: Suicidal ideation and suicide attempts in panic disorder and social phobia. Am J Psychiatry1994;151:882-887.
SUMMARY
Panic disorder is common in the general population. Patients with this disorder often present to the ED. The emergency physician must be able to identify this disorder to initiate proper treatment. The role of the emergency physician and the ED in treatment depends on the patient's ability to overcome this disease. It is important that the emergency physician educate and counsel the patient that this disease process is psychologic and not physical. REFERENCES 1. McGlynn TJ, Metcalf HL {eds); Diagnosisand Treatment of Anxiety Disorder: A Physician's Handbook.Washington DC: American Psychiatric Press, 1991.
2. Panic Disorder."Diagnosis, Treatmentand Management. Washington DC: American Psychiatric Association, 1990. 3. $heehan Dr, Sbeehan KE, Hinichiello WE: Age of onset of phobic disorders: A reevaluation. ComprPsychiatry1981;22:544-553. 4. Robins LN, Relzer JE, Weissrnan MM et al: Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry1984;41:949-958. 5. Ross CA, Waiker JR. Neufeld K, et al: Management of anxiety and panic attacks in immediate care facilities. Gen HeapPsychiatry1988;10:129-131. 6. Markowitz JS, Weissrnan MM, Ovellette R, et ah Quality of life in panic disorder. Arch Gen Psychiatry1989;46:984-992.
24. BarskyAJ, Clary PO, CoeytauxRR, et ah Psychiatric disorders in medical outpatients complaining of palpitations. J Gen Intern Med1994;9:306-313. 25. Sheehan OV: Current concepts in psychiatry: Panic attacks and phobias. N Engl J Mad 1982;307:156-158. 26. OavidsonJR: Continuation treatment of panic disorder with high potency benzodiazepinas.J Clin Psychiatry1990;51(sapplA):31-37. 27. Kirn SW: Panic disorder, in Tintinalli JE, Krorne RL, Ruiz E (ads): EmergencyMedicine: A ComprehensiveStudy Guide. New York: McGraw-Hill, 1989. 28. Garvey M: Benzodiazepinesfor panic disorder: Are they safe? PostgradMad 1991;90:245250. 29. Nagy LM, Krystal JH, Woods SW, et al: Clinical and medication outcome after short-terrn alprazolam and behavioral group treatment in panic disorder. Arch Gen Psychiatry1989;46:993999. 30. OehrbergS, Christiansen PE, RehnkeK, et ah Paroxetine in the treatment of panic disorder. A randomized, double-blind, placebe-contrelled study. BrJPsychiatry1995;167:374-379. 31. Swinson RP, Soulis C, Cox BJ, et al: Brief treatment of emergencyroom patients with panic attacks. Am J Psychiatry1992;149:944-946. 32. ClancyJ, Noyes R Jr: Anxiety neurosis: A disease for the medical model. Psychosomatics 1976;17:90-93. 33. Crowe RR, Neyes R Jr, Wilson AF, eta[: A linkage study of panic disorder. Arch Gen Psychiatry 1987;44:933-937. 34. Katon W: Panic disorder and somatization: Review of 55 cases, Am J Med 1984;77:101-108.
Reprint no. 47/1/81534 Reprints not available from the author.
7. FriedmanS, Paradis CM, Hatch M: Characteristics of African-American and white patients with panic disorder and agoraphobia. Heap CommunityPsychiatry1994;45:798-803.
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Panic Disorder: Diagnosis and Treatment in Emergency Medicine
Receivedfor publicationJuly 17, 1995, Revisions receivedNovember 18, 1995; September 3, 1996; and January 31, 1997. Acceptedfor publication February 3, 1997.
Panic disorder is a newly recognized psychiatric illness involving unexpected, unprovoked attacks of anxiety. Patients with panic disorder commonly seek treatment in the ED, It is important for the emergency physician to properly recognize and categorize this disorder to initiate appropriate treatment, Illness description and treatment guidelines of this disorder are discussed in this article.
Copyright © by the American College of Emergency Physicians.
[Zun LS: Panic disorder: Diagnosis and treatment in emergency medicine. Ann EmergMed July 1997;30:92-96.]
From the Department of Emergency Medicine, Mount Sinai Hospital Medical Center, Chicago, IL.
Leslie S Zun, MD, MBA
INTRODUCTION Panic disorder is a syndrome characterized by unexpected and unprovoked attacks of anxiety that produce both cognitive and physical symptoms. 1 It is the most common anxiety disorder. 2 In the past, many individuals with panic disorder were considered to have generalized anxiety disorder. Patients with panic disorder are commonly seen m the ED. However, the diagnosis is rarely made there. When panic disorder is misdiagnosed, unnecessary tests, inappropriate treatment, and incorrect referrals may result. Emergency physicians should become familiar with the diagnosis and treatment of this newly defined disorder. In this article the clinical presentation, causes, natural history, associations, and treatment of panic disorder are discussed.
EPIDEMIOLOGY The lifetime prevalence of panic disorder in the general population is 1.6%. 3 The disorder has a unimodal distribution, peaking in the third decade of life. Panic disorder affects more females than males. 3,4 It is rarely found in older patients. 4 In the single study of the prevalence of panic disorder treated in the ED, Ross et al 5 found that 4% of all patients presented with psychiatric illness. Of these, 27% had panic disorder. In another study, patients with known, panic disorder were found to be frequent users of EDs. Their rate of
92
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ED use was higher than that of patients with major depression and other psychiatric illnesses. 6 The incidence of panic disorder is similar among whites, blacks, and other racial groups. 4,r However, blacks with this disorder have been reported to have a higher rate of ED visits than whites with panic disorder/It is not known whether the incidence is different in the Hispanic population. However, the disorder termed ataque de nervious (attack of the nerves) has a significant overlap with panic disorder in the Latin American population. 8 PRESENTATION
Panic disorder is common in the general population; therefore patients with this disorder frequently present to the ED. Early recognition facilitates appropriate workup and proper treatment. The major distinguishing feature of panic disorder is the combination of cognitive and physical symptoms. Onset is rapid, peaking within 10 minutes, and the attack lasts about 60 minutes (Figure). The typical patient has two to four attacks per week, often accompanied by anticipatory anxiety.
Figure.
Table.
Differential diagnosis of panic disorder. Panic DisorderSymptom
A patient who sustains four panic attacks in 4 weeks or one or more attacks followed by 4 weeks of continuous anticipatory anxiety may be said to have panic disorder. 1 Panic disorder has several symptoms that are referable to various body systems: chest pain, shortness of breath, palpitations, dizziness, abdominal pain, and nervousness. Patients may have the same symptom complex during each panic attack, or they may display a changing symptom complex. The symptom complex provides a long list of differential diagnoses, including adrenergic excess (Table). Panic disorder was diagnosed in 33% to 59% of patients who presented with chest pain, in 25% to 50% of those who presented with vestibular symptoms, and in 33% who presented with gastrointestinal complaints. 9 Any of the following types of patients may seek treatment in the ED: (1) those with undiagnosed panic disorder who present with a symptom combination consistent with a panic attack, (2) those with known panic disorder who present with their usual symptom combination, and (3) those with known panic disorder who present with an unusual symptom combination. The approach to each of these types of patients varies.
Possible Medical Cause
Chest pain
Angina Myocardial infarction Costochondritis Pleuritis/pneumonia Shortness of breath Hyperventilation Pulmonary embolism Congestive heart failure Chronic obstructive pulmonary disease Palpitations Paroxysmal atrial tachycardia Supraventricular tachycardia Mitral valve prolapse Ventticular paroxysmal contractions Atrial paroxysmal contractions Hyperthyroidism Hypoglycemia Pheochromocytoma Dizziness Orthostatic hypertension Acute anemia Benign positional vertigo Meniere's disease Acute labyrinthitis Numbness Hyperventilation Nervousness Hyperthyroidism Hypoglycemia Modifiedwith permissionfrom McGlynnTJ, Metcalf IlL (eds):Diagnosisand Treatmentof Anxiety Disorders.'A Physician'sHandbook. Copyright© by the AmericanPsychiatric Association,1990.
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Diagnostic criteria for panic disorder. At some time during the disturbance, one or more panic attacks occurred that were unexpected and were ROttriggered by situations in which the person was the focus of attention. Four attacks have occurred during a 4-week period, or one or more attacks have been followed by a period of at least 1 month of persistent fear of having another attack. At least four of the following symptoms occurred during at least one of the attacks: Shortness of breath (dyspnea) or a smothering sensation Dizziness, unsteady feeling, or fainting Palpitations or accelerated heart rate (tachycardia) Trembling or shaking Sweating Choking Nausea or abdominal distress Depersonalization (the feeling that one's body is unreal) or derealization (the feeling that reality is altered) Numbness or tingling sensations (paresthesia) Flushes (hot flashes) or chills Chest pain or discomfort Fear of dying Fear of going crazy or of doing something uncontrolled In one of the attacks, at least four of the symptoms developed suddenly and increased in intensity within 10 minutes of the beginning of the first symptom noticed in the attack. No organic factor (eg, amphetamine or caffeine intoxication, hyperthyroidism} started or maintained the disturbance. Modifiedwith permissionfrom PanicDisorder" Diagnosis, Treatmentand Managemen~ 1990:35-36.Copyright© by the AmericanPsychiatricAssociation.
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PANIC DISORDER ,Zu~.
For patients with undiagnosed panic disorder who present with a symptom combination consistent with a panic attack (diagnostic category 1), the clues to the diagnosis of panic disorder include the patient's age, typical physical and psychologic symptoms, the time it takes the attack to complete its course, and lack of other identifiable causes. These patients need an appropriate evaluation to determine whether an underlying cause for their panic attacks exists. The differential diagnosis is extensive (Table) and includes adrenergic excess. Frequently the diagnosis is made on the basis of exclusion of other possible causes. A patient known to have panic disorder who presents to the ED with the same symptom combination he or she has experienced previously or with a similar one (diagnostic category 2) is most likely having another panic attack. In this instance, it is rare for the patient to require an extensive workup. It is imperative for the emergency physician to recognize that the disorder is psychologic and not to reinforce the patient's belief that something is physically wrong. For patients with known panic disorder who present with a symptom combination that meets the criteria for panic disorder but is different from one exhibited during their usual panic attack (diagnostic category 3), an adequate history and physical examination may be useful in determining that this presentation is another form of a panic attack. Such a diagnosis is easier to make if the presenting attack fits the time course and symptom complex found with panic attacks. If not, a more extensive workup may be necessary if the emergency physician is concerned about possible life- or limb-threatening causes. CAUSES OF PANIC DISORDER
The cause of panic disorder is uncertain. It is believed to be the product of psychologic, behavioral, and biologic forces and is aggravated by stress and conflict. The disease is genetically influenced and has strong biologic correlates. 1< t 1 These correlates originate in the locus caeruleus, [3-aminobutyric acid (GABA) system/benzodiazepine receptor complex, septohippocampal region, and ventromedullary center. The locus caeruleus contains 50% of all noradrenergic receptors in the central nervous system. Stimulation of this area produces sympathetic arousal and an outpouring of catecholamine, possibly leading to panic symptoms.11,12 GABA is a neurotransmitter that decreases neuron excitability. By opening up ion channels in neurons, GABAcauses neuronal hyperpolarization and a decrease in anxiety. Benzodiazepines enhance the action of GABA, producing a calming effect. GABAantagonist can produce the opposite effect. 13
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The septohippocampal region is believed to moderate input from external and internal environments. An input mismatch causes inhibiting behavior. 14 a patient with panic disorder may have a hypersensitivity in this region. Positron emission tomography studies of panic disorder patients revealed a mismatch between the right and left parahippocampal regions not found in patients without this disorder. ~5 The ventromedullary center lacks a significant bloodbrain barrier. It responds to Pco2, pH, and acetate levels in the blood, causing central nervous system arousal. Panic disorder patients have greater sensitivity to carbon dioxide and lactate levels than persons without the disorder. 16 NATURAL HISTORY
The course of panic disorder varies. Patients may progress through six stages. Chronicity is commonly found in this disorder, 17 although 15% of patients may have complete remission. 18 Some patients may stay in one stage, whereas others may progress rapidly through all six stages. Half of the patients present m stage 1, limited-symptom attack. These patients display fewer than the four symptoms necessary for diagnosis of panic disorder. The other 50% of patients present in stage 2, panic attacks. Patients in stage 2 meet the definition of panic disorders with the appropriate frequency, duration, and four or more of the symptoms (Figure). It is believed that if the diagnosis is made in stage 1 or 2 and the patient is properly treated, the disorder is less likely to progress, is Stage 3 is hypochondnasis. A patient m this stage becomes preoccupied with concerns about medical illness, despite medical assurances. The panic attacks may become associated with environmental stimuli. This is known as phobic avoidance behavior. Driving and going to stores or shopping malls are the most frequent fears. 19 Phobic avoidance progresses to stage 4, agoraphobia 0iterally, "fear of the marketplace," or fear of where people assemble). Lelliott et al 2° found that m 23% of cases, agoraphobia was preceded by phobic avoidance. In 32% of cases, agoraphobia developed a few days after the first panic attack. In 41% of cases, agoraphobia developed after more than one panic attack and was present 1 week to 1i years tater. 2° As the disease progresses to stage 5, extensive phobic avoidance, these types of phobic behaviors develop. Stage 5 patients may become housebound. Stage 6, secondary depression, is believed to result from progressive disability and demoralization. Other authors have classified panic disorder differently. Weinstock 2 t classifies panic disorder into spontaneous
ANNALS OF EMEF{6ENCY MEDICINE
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attacks, situational attacks, panic attacks during sleep, and panic attacks with and without agoraphobia. ASSOCIATIONS
Panic disorder is associated with several other disorders, including sleep and eating disturbances, hyperventilation, alcoholism and substance abuse, suicide, mitral valve prolapse, and cardiovascular disease. It is also closely associated with depression, obsessive-compulsive disorder, and generalized anxiety disorder. Patients tend to fear the activities they are engaged in when a panic attack occurs. In other words, sleeping or eatmg disturbances may evolve in patients who have panic attacks while eating or sleeping. Acute and chronic hyperventilation is related to panic disorder. Although the exact relationship is obscure, hyperventilation causes panic attacks in some patients. 19 When a hyperventilating patient with panic disorder breathes into a paper bag, the CO 2 level is increased. This increase can precipitate a panic attack. Instead, the patient should be coached to reduce breathing to l0 breaths per minute.19 Panic disorder patients tend to self-medicate with alcohol and other substances to reduce the number of panic attacks. 22 These patients have a higher rate of alcohol and substance abuse than patients with other psychiatric illnesses. 6 Cocaine intoxication and withdrawal, marijuana use, and alcohol and opiate withdrawal may worsen panic disorder. 19 Suicidal ideation and suicide attempts are frequent in panic disorder patients. Cox et a123 found that 37% of patients with panic disorder had had suicidal ideation in the preceding year and that 18% had a lifetime incidence of suicide attempts. Suicidal ideation is associated commonly with secondary depression. TREATMENT
Treatment of panic disorder includes patient education, behavioral therapy, and pharmacologic therapy. Psychotherapy has not proven effective in the treatment of this disorder. 24 With the proper treatment, more than 85% of patients can become symptom free. 9 The patient must understand the illness to be reassured that the symptom pattern is characteristic of the disorder. The patient also nmst understand that with proper treatment, the panic attacks can be controlled. The National Institute of Mental Health has a hotline (800-64-PANIC) for panic disorder patients and their families. Pharmacologic treatment includes benzodiazepines, tricyclic antidepressants, and monoamine oxidase inhibitors.
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Alprazolam, a benzodiazepine, is commonly used.l,19,25-29 This drug is usually started at low doses (.25 rag, three times a day), but doses of 4 rag/day or more may be required. 26 Tricyclic antidepressants imipramine and desipramine are effective in the treatment of panic disorder. Newer antidepressants such as fluoxetine, clominparamine, and paroxetine have also been found to be effective, x7,3° Buspirone hydrochloride and [~-blockers have not been found to be effective. Behavioral therapy is useful for patients in the phobic avoidance stages. Once the patient is symptom-free for several weeks after pharmacologic treatment, the physician should encourage the patient to face the phobic stimuli. W'hen the phobias are long-standing and severe, more formal behavior therapy is necessa U. In the only study of panic disorder treated in the KD, Swinson et aP 1 enrolled patients from the ED in one of two treatment arms. Patients received reassurance or exposure instructions about confronting the situation in which the attack occurred. Although medications were not used in this study, the authors found that early intervention and exposure instructions reduced long-term consequences of panic attacks. Reassurance was not found to be as effective. Treatment of panic disorder depends on the patient's diagnostic category Patients in diagnostic category i should be reterred to a primary care physician or psychiatrist familiar with panic disorder. A short course of a benzodiazepine may be prescribed. For patients in diagnostic category 2, it is imperative for the emergency physician to recognize the disorder and to not reinforce the patient's belief that something is physically wrong. The emergency physician should explain to the patient that the panic disorder is causing the symptoms. These patients should be referred back to their treating psychiatrist or primary care physician. After a proper workup to verify panic attacks as the cause of the patients' complaints in category 3, the emergency physician should consult the primary care physician or psychiatrist to determine whether a dosage increase of the patient's psychoactive medication is warranted. COMPLICATIONS
Panic disorder is frequently misdiagnosed in general practice. Kahn 9 commented on a large study in which 70% of the patients with panic disorders had seen more than 10 consultants before the correct diagnosis was made. In another study, the most frequent consultations were from cardiology, neurology, and gastroenterology. 3x Misdiagnosis of panic disorder in the ED is costly. This issue is of particular importance in diagnostic categories 2
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and 3. The ED diagnosis of category 2 is frequently made without difficulty. Therefore limited testing or no testing is warranted. However, the patients in categories 1 and 3 present more of a diagnostic challenge. For patients m category 1, an initial workup must be performed to rule out organic causes. For patients in category 3, testing may be indicated, depending on clinical judgment. Inappropriate tests are often ordered for patients with panic disorder. Of patients seeking treatment in an immediate care center, laboratory testing was performed in 43% of cases. 5 Electrocardiography, CBC, and assays of blood urea nitrogen, electrolyte, and glucose level concentrations are the most commonly performed laboratory tests. 5 It should be noted that Swinson et al 3~ did not differentiate the patients into diagnostic categories. Patients with panic disorder are frequently referred to medical clinics instead of psychiatric clinics. A study of patients referred to a cardiology clinic revealed that 28% had panic disorder. 33 In another study of patients undergoing angiography for anginalike chest pain, the authors found that in 33%, the pain was a result of panic disorderY Not only is panic disorder misdiagnosed in the ED, the correct treatment is rarely prescribed in the ED. In the study by Ross etal, 5 14% of patients with panic disorder received anxiolytics, and none was referred to a psychiatrist.
8. Liebowitz MR, Slaman E, Jasine CM, et al: Ataque de nervieas and panic disorder. Am J Psychiatry 1994;151:871-875. 9. Khan B: Panic disorder. West J Marl 1991;155:517-518, 10. Torgersen S: Genetic factors in anxiety disorders. Arch Gen Psychiatry1983;40:1085-1089. 11. Redmond DE Jr, HuangYH, Snyder DR, et ah Behavioral effect of stimulation ef the nucteus locus coeruleus in the stump tailed monkey Macaca arctoidas. Brain Res 1976;116:502-51O. 12. CharneyDS, Woods SW, Nagy LM, at. al: Noradrenergic function in panic disorder. J Clin Psychiatry 1996;51(aupplA):5-11. 13. Insal TR, Ninan, PT, Aloy J, et al: A benzodiazepinereceptor mediated medal of anxiety: Studies in non-human primates and clinical implications. Arch Gen Psychiatry1984;41:741-750. 14. Gray JA: The Neuropsychologyof Anxiaty: An Inquiry Into the Functionsof the Septohippocampal System. Oxford: Oxford University Press, 1982. 15. Raiman EM. Raichle ME, Butler FK, et aL: A focal brain abnormality in panic disorder. Nature 1984;310:683-885, 16. Carr OB, Sheehan DV: Panic anxiety: A new biological disorder. J Clin Psychiatry 1984;45:323-330. 17. Pollack MH, Otto MW, RosenhaarnJF, etal: Longitudinal coarse of panic disorder: Findings from the Massachusetts General Hospital Naturalistic Study. J Clin Psychiatry1990;51:(suppl A):12-16. 18. Noyes R Jr, Ciancy J, Hoenk PR, et al: The prognosis of anxiety neurosis. Arch Gen Psychiatry 1988;37:173-178. 19. Uhde TW, Nemiah JO: Anxiety disorders, in Kaplan HI, Sadech DJ (eds): Comprehensive Textbookof Psychiatry, ed 5. Baltimore: Williams & Wilkins, 1989. 28. Lelliott P, Marks I, McNamee G, et al: Onset of panic disorder with agoraphobia: Toward an integrated mode. Arch Gen Psychiatry1989;46:1000-1084. 21. Weinsteck RS: Panic disorder. Am FaroPhysician1995;52:2055-2063. 22. Bibb JL, ChambersDL: Alcohol use and abuse among diagnosed agoraphobics. BehavRes Thor 1986;24:49-68. 23. Cox BJ, Oirenfeld DM, Swinson RP, et al: Suicidal ideation and suicide attempts in panic disorder and social phobia. Am J Psychiatry1994;151:882-887.
SUMMARY
Panic disorder is common in the general population. Patients with this disorder often present to the ED. The emergency physician must be able to identify this disorder to initiate proper treatment. The role of the emergency physician and the ED in treatment depends on the patient's ability to overcome this disease. It is important that the emergency physician educate and counsel the patient that this disease process is psychologic and not physical. REFERENCES 1. McGlynn TJ, Metcalf HL {eds); Diagnosisand Treatment of Anxiety Disorder: A Physician's Handbook.Washington DC: American Psychiatric Press, 1991.
2. Panic Disorder."Diagnosis, Treatmentand Management. Washington DC: American Psychiatric Association, 1990. 3. $heehan Dr, Sbeehan KE, Hinichiello WE: Age of onset of phobic disorders: A reevaluation. ComprPsychiatry1981;22:544-553. 4. Robins LN, Relzer JE, Weissrnan MM et al: Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry1984;41:949-958. 5. Ross CA, Waiker JR. Neufeld K, et al: Management of anxiety and panic attacks in immediate care facilities. Gen HeapPsychiatry1988;10:129-131. 6. Markowitz JS, Weissrnan MM, Ovellette R, et ah Quality of life in panic disorder. Arch Gen Psychiatry1989;46:984-992.
24. BarskyAJ, Clary PO, CoeytauxRR, et ah Psychiatric disorders in medical outpatients complaining of palpitations. J Gen Intern Med1994;9:306-313. 25. Sheehan OV: Current concepts in psychiatry: Panic attacks and phobias. N Engl J Mad 1982;307:156-158. 26. OavidsonJR: Continuation treatment of panic disorder with high potency benzodiazepinas.J Clin Psychiatry1990;51(sapplA):31-37. 27. Kirn SW: Panic disorder, in Tintinalli JE, Krorne RL, Ruiz E (ads): EmergencyMedicine: A ComprehensiveStudy Guide. New York: McGraw-Hill, 1989. 28. Garvey M: Benzodiazepinesfor panic disorder: Are they safe? PostgradMad 1991;90:245250. 29. Nagy LM, Krystal JH, Woods SW, et al: Clinical and medication outcome after short-terrn alprazolam and behavioral group treatment in panic disorder. Arch Gen Psychiatry1989;46:993999. 30. OehrbergS, Christiansen PE, RehnkeK, et ah Paroxetine in the treatment of panic disorder. A randomized, double-blind, placebe-contrelled study. BrJPsychiatry1995;167:374-379. 31. Swinson RP, Soulis C, Cox BJ, et al: Brief treatment of emergencyroom patients with panic attacks. Am J Psychiatry1992;149:944-946. 32. ClancyJ, Noyes R Jr: Anxiety neurosis: A disease for the medical model. Psychosomatics 1976;17:90-93. 33. Crowe RR, Neyes R Jr, Wilson AF, eta[: A linkage study of panic disorder. Arch Gen Psychiatry 1987;44:933-937. 34. Katon W: Panic disorder and somatization: Review of 55 cases, Am J Med 1984;77:101-108.
Reprint no. 47/1/81534 Reprints not available from the author.
7. FriedmanS, Paradis CM, Hatch M: Characteristics of African-American and white patients with panic disorder and agoraphobia. Heap CommunityPsychiatry1994;45:798-803.
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