Problems in Family Practice

Panic Disorder

Brian Grant, MD, Wayne Katon, MD, and Bernard Beitman, MD Seattle, Washington

Panic disorder is a subtype of manifested by discrete periods of apprehension or and at least four of the follow­ ing somatic symptoms: dyspnea, , chest , , , or experi­ ence, , hot and cold flashes, sweating, faintness, trembling, and fear of dying, going crazy, or doing something uncontrolled during an attack. Because the patient with panic disorder often selectively focuses on one of these somatic symptoms and may minimize or deny psychosocial distress, panic disorder is frequently misdiagnosed. As a result of the frightening nature of the symptoms, a pattern of overutilization of medical care systems frequently ensues. Panic disorder is usually precipitated by stressful life events, most commonly separation or loss, in a patient with a genetic or acquired vul­ nerability. As with other psychophysiologic illness (, duodenal ulcer) resolution of the acute stressful life event may not lead to resolutions of the physiologic changes. Two spe­ cific tricyclic , and desipramine, have been shown to be effective therapeutic agents in treating panic disorder.

Primary care physicians currently treat an esti­ 526.196 patient visits to 118 family physicians.3 mated 60 percent of the patients with mental ill­ Anxiety alone was the fifth most common diag­ ness in the United States.1 Patients with psychi­ nosis in this study. Antianxiety in atric illness obtain two to four times as much general and in particular have nonpsychiatric medical care as patients without consistently been the most frequently prescribed such diagnoses.2 Anxiety and depression consti­ medications in the United States over the last 10 tuted 86.8 percent of the psychiatric problems years, and primary care physicians wrote the ma­ seen in a large computer-based study in Virginia of jority of these prescriptions.4 In 1971, a National Institute of study determined that 15 percent of the United States population had taken at least a single dose of an antianxiety medi­ From the Division of Consultation-Liaison , De­ partment of Psychiatry and Behavioral Sciences, School of cation in the last year.'’ Medicine, University of Washington, Seattle, Washington. This paper will focus on a particular Requests for reprints should be addressed to Dr. Wayne Katon, Division of Consultation-Liaison Psychiatry, Depart­ subtype of anxiety, panic disorder, which is ment of Psychiatry and Behavioral Sciences, RP-10, School uniquely treatable by a combination of of Medicine, University of Washington, Seattle, WA 9819b.

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attack. During this second phase, events and cir­ tients visit multiple medical specialists. Jn one cumstances associated with the attacks may be large study of panic disorder patients, 70 percent selectively avoided, leading to specific phobic be­ had visited more than 10 physicians.13 haviors. For example, a person who developed an An association between mitral valve prolapse attack during public speaking may avoid such an (MVP) and panic attacks has been observed. Sev­ activity. The third stage of panic disorder is the eral studies have confirmed an incidence of mitral most disabling, the development of . valve prolapse in 32 to 47 percent of patients diag­ In agoraphobia the patient develops a fear of going nosed as having panic disorder.25'27 It is unclear outside his home and becomes incapacitated as a whether mitral valve prolapse predisposes a pa­ result of the association of panic attacks with tient to panic disorder or whether panic disorder many different stimuli. Also, agoraphobic patients causes MVP. The recent finding that patients with often avoid being alone and desperately cling to have an increased rate of MVP others for comfort. that does not disappear with treatment and return to the euthyroid state is suggestive evidence that a hyperdynamic /3-adrenergic state may have an etiologic role in MVP.28 However, patients with mitral valve prolapse and panic disorder respond to treatment with imipramine as well as patients Diagnostic Problems with panic attacks alone.29 Patients with panic disorder often choose to seek help in a setting consistent with their own explanatory model of what is happening to them. Those who perceive the symptoms as a threat pri­ marily to their mental health might focus on the affective and cognitive symptoms of fear and . These individuals may consequently con­ The patient, because of the possibility of a co­ sult many of the large variety of psychotherapists, existing physical disorder, warrants a complete including psychiatrists, psychologists, or social history and physical examination. In a patient with workers operating within the recognized mental a known medical ailment, that illness (including health system. Many other patients focus selec­ the symptoms, complications, and pharmacologic tively on their physical symptoms because they treatment) should always be suspected.30 For in­ are unable to justify within their personal or cul­ stance an asthmatic patient with a toxic amino- tural belief systems seeking help for “mental phylline serum level, a diabetic patient with illness.” These individuals are more likely to con­ hypoglycemic episodes, and a patient with the sult the primary care physician when faced with cardiac illness paroxysmal atrial may the symptoms of panic disorder. There are many all suffer from symptoms that are very similar reasons for this phenomenon: the health care pro­ to the patient. Panic attacks have fession as a whole is biologically oriented, paying also been associated with endocrinologic changes more heed to disorders felt to be physiologically including oophorectomy, hysterectomy, the post­ based.23 This reflects a similar cultural partum period, and initiation of thyroid replace­ bias whereby people learn early in life that they ment for hypothyroidism. Other physical dis­ are more likely to be taken seriously and consid­ orders that may cause symptoms resembling a ered legitimately ill if they are physically . panic attack include hypoglycemia, pheochromo- Also, the most frightening aspects of the syn­ cytoma, hyperthyroidism, cardiovascular , drome, such as chest tightness, tachycardia, caffeinism, and drug intoxication and withdrawal. dyspnea, diaphoresis, tremulousness, and dizzi­ Initial panic attacks are also often precipitated by ness, are somatic manifestations probably caused recreational use of marijuana, amphetamines, or by a burst of catecholamines into the blood cocaine. stream. In fact, isoproterenol infusion has been One of the most difficult differential diagnoses found to induce panic attacks that can be reversed occurs when panic attacks develop concomitantly with propranolol infusion.24 Typically such pa- with a known physical illness such as asthma or

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Table 3. DSM III Criteria for Generalized acute panic attacks or specific . Simple involves a persistent irrational fear of and compelling to avoid an object or specific Generalized, persistent anxiety is manifested situation other than being alone. Simple phobias by symptoms from three of the following are sometimes referred to as “ specific” phobias, categories: the most common ones in the general population 1. Motor tension: Shakiness, jitteriness, jump­ iness, trembling, tension, muscle aches, involving animals, particularly dogs, snakes, and fatigability, inability to relax, eyelid twitch, mice. Other simple phobias are furrowed brow, strained face, fidgeting, (fear of closed spaces) and acrophobia (fear of restlessness, easy startle heights). Psychosocial trauma can almost always 2. Autonomic hyperactivity: Sweating, heart be identified as the original precipitant (eg, being pounding or racing, cold, clammy hands, bitten by a dog as a child may cause a phobia to all dry mouth, dizziness, light-headedness, dogs). When exposed to a phobic stimulus, the paresthesias (tingling in hands and feet), patient may experience symptoms identical to upset stomach, hot or cold spells, frequent those of a panic attack, but patients with simple urination, diarrhea, discomfort in the pit of phobia do not have panic attacks when not ex­ the stomach, lump in the throat, flushing, posed to their specific phobic stimulus. pallor, high resting pulse and respiratory Major depression may be diagnosed by the pro­ rate longed presence of depressed mood and at least 3. Apprehensive expectation: Anxiety, worry, four of the following vegetative and cognitive fear, rumination, and of misfor­ symptoms: appetite disturbance, sleep disturb­ tune to self or others 4. Vigilance and scanning: Hyperattentiveness ance, or retardation, anhe- resulting in distractibility; difficulty in con­ donia, decreased libido, loss of energy, thoughts centrating, , "on edge," ir­ of worthlessness or , decreased ability to ritability, impatience think or concentrate, or suicidal thoughts (Table The anxious mood has been continuous for at 4). Many patients have major depression and panic least one month disorder concurrently, and the panic attacks will Not due to another , such as resolve with successful treatment with a tricyclic depressive disorder or that acts on the noradrenergic At least 18 years of age system. Patients with panic attacks often self-medicate Source: Diagnostic and Statistical Manual of with alcohol and hypnotics, resulting at Mental Disorders18 times in abuse of these general central nervous system depressants.31 Several studies have dem­ onstrated a very high incidence of panic disorder in the alcoholic population, and thus this popula­ angina pectoris. Both of these illnesses normally tion should be carefully screened for the presence cause anxiety in the patient, which is a signal of of panic attacks.32 Symptoms of generalized anx­ physical distress, but they also are occasionally iety as well as acute panic often are integral symp­ toms of or alcohol withdrawal exacerbated by the development of pathological syndromes, and the patient must always be ques­ anxiety, ie, panic attacks. Psychiatrically, care should be exercised to dif­ tioned about past drug use. ferentiate among the symptoms of panic disorder and those of generalized anxiety, simple phobia, and depression. The symptoms of generalized anx­ iety disorder are persistent anxiety with three of the four following symptoms: motor tension, au­ tonomic hyperactivity, apprehensive expectation, Treatment vigilance, and scanning (Table 3).1X These symp­ Upon concluding that the patient does meet the toms must be present for at least one month, and criteria for panic disorder, as well as excluding co- the patient with generalized anxiety does not have

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Table 4. Diagnostic Criteria for Major medication may be useful. However, when the Depressive Disorder symptoms have progressed to include anticipatory anxiety or agoraphobia, supportive or behavioral A. Dysphoric mood or loss of or pleas­ directed toward these symptoms ure in all or almost all usual activities and may be needed. pastimes. The dysphoric mood is charac­ As is common in patients presenting with an terized by terms such as depressed, sad, illness, there is a feeling of fear with apprehension blue, hopeless, down in the dumps, irritable of bad, or even terminal, outcome and a sense of B. At least four of the following symptoms have loss of control. By its very name, panic disorder each been present nearly every day for a period of at least 2 weeks: signifies an overwhelming sense of helplessness in 1. Poor appetite or significant weight loss the face of frightening and foreboding symptoms. (when not dieting) or increased appetite The physician, who is satisfied that a life-threaten­ or significant weight gain ing emergency is not present, should reassure the 2. Insomnia or patient that his illness is extremely uncomfortable 3. Psychomotor agitation or retardation but one that is treatable with proper medication. (but not merely subjective of This effort, combined with a statement that the restlessness or being slowed down) symptoms will subside and that treatment is avail­ 4. Loss of interest or in usual ac­ able and effective, will provide great comfort and tivities, or decrease in sexual drive not to many patients. A subgroup of patients limited to a period when delusional or who are extremely somatically oriented will reject hallucinating 5. Loss of energy; fatigue the physician diagnosis of panic disorder because 6. Feelings of worthlessness, self-reproach, of the cultural stigma to mental illness and the or excessive or inappropriate guilt profound physiologic changes the panic syndrome (either may be delusional) causes. 7. Complaints or evidence of diminished A useful tool in both confirming diagnosis and ability to think or concentrate, such as negotiating treatment is to have the patient hyper­ slowed thinking, or indecisiveness not ventilate for two to five minutes, which will usual­ associated with marked loosening of ly precipitate all of the symptoms of a panic anxi­ association or incoherence ety attack, and then have the patient breathe into 8. Recurrent thoughts of , suicidal a paper bag with a calming suggestion by the phy­ ideation, wishes to be dead, or suicide attempt sician that the symptoms will quickly abate. C. Neither of the following dominates the clin­ is a core part of panic disorder, ical picture when an affective syndrome is and this clinical trial not only confirms diagnosis absent (ie, symptoms in criteria A and B but is a powerful, convincing tool demonstrating above): to the patient and his family that the overwhelming 1. Preoccupation with a mood-incongruent frightening symptoms are not dangerous and can or be controlled and treated.33 2. Bizarre behavior Reassurance and demonstration of the onset of D. Not superimposed on schizophrenia, symptoms with hyperventilation, while important, schizophreniform disorder, or a paranoid may have minimal effect without a demonstrated disorder ability to pharmacologically treat the patient. By E. Not due to any organic mental disorder or uncomplicated bereavement the time the patient has sought counsel, he or she is aware that something is quite wrong and that previously normal activities such as taking a test, going for a walk, or attempting to sleep invoke new-found terror. Specific medications have been found to support the clinician's reassurances. Ef­ existing medical or psychiatric disorders, treat­ fective medications include specific tricyclic anti­ ment may be undertaken. Choice of treatment de­ depressants (imipramine and desipramine) and the pends upon the stage in which the disorder is monamine oxidase inhibitors (MAOIs) encountered. In all three stages, support and and tranylcypromine. There is also recent re-

THE JOURNAL OF FAMILY PRACTICE, VOL. 17, NO. 5, 1983 PANIC DISORDER search that suggests that , a new benzo­ diazepine, is an effective medication in the treat­ the adverse consequences of panic and gradually expand a life that has been constricted by the ment of panic disorders.34 panic attacks. Imipramine has a recognized effectiveness in Most patients will respond within weeks to the treatment of panic attacks. While commonly treatment of simple panic disorder but not neces- used as an antidepressant in standard maintenance saiily to reduction of their anticipatory anxiety doses of 100 to 300 mg, the dosage effective in and agoraphobic pattern. The clinician may wish treatment of panic disorder is much lower, 25 to to consider psychiatric consultation in refractory 200 mg. An appropriate initial dose of imipramine patients and in patients whose diagnosis remains or desipramine in this disorder is 25 mg daily. less clear. In addition, the clinician must be pre­ Some patients are exquisitely sensitive to this pared for family repercussions in the treatment of medication and may develop jitteriness, irritabil­ any behavioral disturbance, as the symptoms may ity, or inability to fall asleep. For these individuals have begun to fulfdl a role in the family environ­ the dosage should be dropped to as low as 5 mg. ment, and their resolution will other mem­ Patients who do not respond to 25 mg should have bers. Many patients who have been chronically ill weekly increases in their dosage of 25 mg. In some with panic attacks may unconsciously sabotage cases patients respond only at a higher antidepres­ treatment because of secondary gains that have sant level of 150 to 300 mg. developed in the family such as increased nurtur- For patients with major depression and panic ance by a formerly distant spouse, avoidance of attacks, the noradrenergic antidepressants (imip­ conflict secondary to the patient symptoms, and ramine, desipramine) are the medications of increased fulfillment of dependency needs. Pa­ choice but should be prescribed in antidepressant tients who wish to examine more closely the pre­ dosages. cipitating factors and possible meanings of their Monamine oxidase inhibitors may be consid­ symptoms may want to embark upon a longer ered a second-line drug in the treatment of panic term insight-oriented psychotherapy. disorder. Though effective, the necessity of avoid­ ing foods high in tyramine, because of the poten­ tial of inducing a hypertensive crisis, makes them less likely to be chosen for use by many patients. On the other hand, M AOIs are at least as effective Conclusions as tricyclic antidepressants in the treatment of panic disorder and generally have fewer side As a result of the severe autonomic nervous system manifestations, panic disorder has often effects. The minor tranquilizers (benzodiazepines) are been misdiagnosed as primarily a physical disor­ der. Patients who focused on cardiac symptoma­ felt to be ineffective or inferior to imipramine, des­ tology have been described in the literature as sul- ipramine, and MAOIs in the treatment of panic fering from irritable heart or effort syndrome, disorder with associated generalized anxiety state. hyperdynamic /3-adrenergic state, pseudoangina, However, these drugs, if employed, should be or most recently, mitral valve prolapse. If dyspnea used on a time-limited basis as an adjunct to or other respiratory symptoms predominate, the psychotherapy. term hyperventilation syndrome was often used. Both supportive and behavioral psychotherapy With gastrointestinal symptoms of diarrhea, con­ are useful and effective in treating the interper­ stipation, bloating, and , irritable colon or sonal problems, anticipatory anxiety, and avoid­ spastic colitis were the diagnostic terms used. Cer­ ance behaviors developed by patients with panic tainly the increased specialization of medicine has disorder. Once medication stops the panic attacks, been partially responsible for the lack of recogni­ supportive and behavioral psychotherapy aimed at tion of panic disorder as a syndrome that, like de­ re-exposure to phobic stimuli the patient has been pression, can be diagnosed from clinical history avoiding because of the association of the stimuli but is often masked by physical symptomatology . with panic attacks should be undertaken. Thus, Panic disorder is a classic psychophysiologic the patient is encouraged to re-enter feared situa­ illness with stressful life events precipitating tions so that he can then experience them without

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tional disorders in a primary care settinq Int iu ., measurable physiological changes that become au­ Health 8:30, 1979 9- lnt J Mental tonomous from the original stressful life events. 7. Sheehan DV, Sheehan KF, Minichiello WE- A™ < onset of phobic disorders: A reevaluation. ComDr An apt analogy can be made to peptic ulcer dis­ try 22:544, 1981 "Pr t'sychia- ease. As in peptic ulcer disease, there is a multi­ 8. Cohen ME, Bodal DW, Kilpatrick A, et al- The hint, familial prevalence of neurocirculatory asthenia Am m. modal etiology with both genetic susceptibility and Genet 3:126, 1951 stressful life events influencing initial incidence. 3. vvuuu r. Ud sublet s synorome or effort syndrome: Once either panic attacks or peptic ulcer develops, Br Med J 1:762, 1941 wnarome). 10. Crowe RR, Pauls DL, Slymen DJ, et al- A familu these pathological physiologic changes may not be study of anxiety . Arch Gen Psychiatry 37-77 iqin alleviated with resolution of life . In fact, 11. Cohen ME, Badal DW, Kilpatrick A, et al- The hinh familial prevalence of neurocirculatory asthenia (anxietv these illnesses, because of their frightening and neurosis, effort syndrome). Am J Hum Genet 3T26 iqk y discomforting symptomatology, cause significant 12. Raskin M, Peeke HVS, Dickman W: Panic and aen eralized anxiety disorders. Arch Gen Psychiatry 39 687 distress to the patient, often affecting key biologi­ cal systems such as sleep, appetite, and sexual 13. Sheehan DV, Ballenger J, Jacobsen G: Treatmentof endogenous anxiety with phobic, hysterical, and hyno drive, as well as adversely affecting the patient's chondriacal symptoms. Arch Gen Psychiatry 37.51, iggg social, vocational, and family functioning. Stress­ 14. Coryell W, Noyes R, Clancy J: Excess mortality in panic disorders. Arch Gen Psychiatry 39:701, 1982 ful life events, easily coped with in the past, may 15. Pitts FN Jr, McClure JN Jr: Lactate in now precipitate abdominal pain in the peptic ulcer anxiety neurosis. N Engl J Med 277:1329, 1967 16. Noyes R, Clancy J, Crowe RR, et al: The familial patient or a flurry of panic attacks in the patient prevalence of anxiety neurosis. Arch Gen Psvchiatrv T with panic disorder. 1057,1978 y 17. Appleby IL, Klein DF, Suchau EJ, et al: The biochem­ Thus it is important to treat the patient with ical indices of lactate induced anxiety. In Klein DF, Rabbin peptic ulcer and panic attacks pharmacologically JG (eds): Anxiety Revisited. New York, Raven Press, 1980 18. Diagnostic and Statistical Manual of Mental Disor­ to decrease the physiologic symptoms that are ders, ed 3. Washington, DC, American Psychiatric Associa­ themselves a cause of significant psychological tion, 1980 19. Shader Rl, Goodman M, Gever J: Panic disorders: distress. In addition, counseling by the primary Current perspectives. J Clin Psychopharmacol 2(sudd| 6I care physician may decrease symptoms as a result 25, 1982 20. Klein DF: Delineation of two drug-responsive anx­ of the provided as well as lead to iety syndromes. Psychopharmacologia 5:397, 1964 improved coping mechanisms that enable the pa­ 21. Klein DF: Anxiety reconceptualized. Compr Psychia­ try 21:411, 1980 tient to decrease his or her own stress. Adjunctive 22. Geyman J, Katon W: Anxiety. In Rakel RE (ed): treatment with relaxation exercises, self-hypnosis, Family Practice, ed 3. Philadelphia, WB Saunders, 1983 23. Katon W, Kleinman A, Rosen G: Depression and or biofeedback may also decrease anxiety and somatization: Part II. Am J Med 72:241, 1982 dampen physiological . As does peptic 24. Easton JD, Sherman DG: Somatic anxiety attacks and propranolol. Arch Neurol 33:689, 1976 ulcer disease, panic disorder tends to be a relaps­ 25. Kantor JS, Zitrin CM, Zelds SM: Mitral valve pro­ ing, remitting illness. Thus, the physician needs to lapse syndrome in agoraphobic patients. Am J Psychiatry 137:467, 1980 monitor further symptomatology, especially at 26. Parises SF, Jones BA, Pinta ER, et al: Panic attacks: times of stressful life changes. Diagnostic evaluation of 17 patients. Am J Psychiatry 136: 105, 1979 27. Crowe RR, Pauls DL: Panic disorder and mitral valve prolapse. In Klein DF, Rabbin J (eds): Anxiety: New Re­ search and Changing Concepts. New York, Raven Press, 1981, pp 103-116 28. Channick BJ, Adlin VE, Marks A, et al: Hyperthyroid­ References ism and mitral-valve prolapse. N Engl J Med 305:497,1981 1. Regier DA, Goldberg ID, Taube CA: The de facto US 29. Gorman JM, Fyer AF, Glicklich J, et al: Mitral valve mental health services system. Arch Gen Psychiatry 35-685 prolapse and panic disorders. Effects of imipramine. In 1978 Klein DF, Rabbin JG (eds): Anxiety Revisited. New York, 2. Hankin J, Oktay JS: Mental disorder and primary Raven Press, 1980 medical care: An analytic review of the literature. In Na­ 30. Rosenbaum JF: The drug treatment of anxiety. tional Institute of Mental Health (Rockville, Md): Series D, N Engl J Med 7:401, 1982 No. 7. DHEW publication No. (ADM)78-661. Government 31. Quitkin F, Rifken A, Kaplan T, et al: Phobic anxiety Printing Office, 1979 syndrome complicated by drug dependency and addiction. 3. Marsland DW, Wood M, Mayo F: A data bank for Arch Gen Psychiatry 27:159, 1972 patient care, curriculum, and research in family practice: 32. Strain JJ, Liebowitz MR, Klein DF: Anxiety and 526,196 patient problems. J Fam Pract 3:25, 1976 panic attacks in the medically ill. Psych Clin North Am 4. Hollister LE: A look at the issues: Use of minor tran­ 4:333 1981 quilizers. Psychosomatics 21 (suppl):4, 1980 33. Compernolle T, Hoogduim K, Joele L: Diagnosis 5. Parry HJ, Balter MB, Mellinger GD, et al: National and treatment of the hyperventilation syndrome. Psycho­ patterns of psychotherapeutic drug use. Arch Gen Psychia­ somatics 20:612, 1979 . try 28:769, 1973 34. Sheehan DV: Current perspectives in the treatment 6. Goldberg D: Detection and assessment of emo­ of panic and phobic disorders. Drug Therapy 9:49, 19°3

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