Panic Disorder

American Family Physician

Panic Disorder RAYMOND S. WEEvFSTEIN, M.D., Potomac Hospital, Woodbridge, Virginia Panic disorder is a chronic iliness that affects at least 3 percent of the population. Panic disorder is associated with significant morbidity and an increased risi< of suicide. Patients generally present with multiple somatic and psychologic complaints, including heart palpitations, chest pain, tremor, shortness of breath, choking, nausea or abdominal distress, dizziness, derealization, fear of losing control or going crazy, fear of dying, paresthesias, chills or hot flushes, headache, diarrhea, insomnia, chronic fatigue, anxiety and depression. To make the correct diagnosis, these symptoms must be evaluated carefully since they also occur with serious cardiovascular, pulmonary, endocrinologic and neurologic disorders. Many effective treatments are available, including tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, benzodiazepines such as alprazolam and donazepam, and psychotherapy.

Panic disorder is a specific illness characterized by episodic panic attacks associated with anticipatory anxiety and phobic avoidance between episodes. Conditions similar to what is now known as panic disorder have been described in the medical literature for over 200 years. In 1895, Sigmund Freud suggested that anxiety disorder should be considered a separate entity, and he referenced the term "anxiety neurosis" in the medical literature.^ Other earlier labels for this syndrome are "cardiac neurosis," "effort syndrome," "vasomotor neurosis," "nervous exhaustion," "irritable heart," "soldier's heart" and "neurasthenia."^ Panic disorder is now recognized as a See editorial on page 1999. November 15,1995

potentially serious condition that can negatively affect a person's lifestyle, ability to work and interpersonal relationships, and it is associated with a significantly increased risk of suicide.^* The age of onset is usually 18 to 45 years, with a median age of about 28 years; however, the disorder can also develop during adolescence.'' The attacks consist of discrete episodes of intense generalized discomfort, fear or anxiety, accompanied by a cluster of predictable somatic symptoms, all of which are related to adrenergic excess. Panic attacks typically last less than one hour, but in rare cases they may persist for several hours. According to criteria presented in the Diagnostic and Statistical Manual of Mental

Disorders (DSM-III-R and DSM-IV),**-^ the diagnosis of a panic attack requires the abrupt development of at least four of the symptoms listed in Table 1, with peaking ofthese symptoms within 10 minutes of onset. Other common symptoms not included in the DSM-DI-R or DSM-IV criteria are listed in Table 2. Organic disease must be ruled out before a definitive diagnosis of panic disorder is made. The differential diagnosis of panic disorder is given in Table 3. Classification of Panic Attacks Over the years, many attempts have been made to classify panic attacks on the basis of severity, perceived cause, time of occurrence and association with other mental illnesses. The classifications most commonly used today are spontaneous attacks, situational attacks, panic attacks occurring during sleep,ând panic attacks with and without agoraphobia.^"^" 2055

American Family Physician Panic Disorder

these forms of panic is the irrational fear of losing control or going crazy. Panic attacks during sleep cause persons Sjonptoms in Diagnostic Criteria to awaken suddenly with the same disfor Panic Attacks* tressing symptoms that occur with attacks during waking hours.^° These individuals Palpitations, pounding heart or accelerated heart may also start having anticipatory bedtime rate anxiety or panic attacks. Sweating Agoraphobia is the fear of being in "unTrembling or shaking safe" public surroundings while losing Sensations of shortness of breath or smothering Feeling of choking control or of being humiliated because of Chest pain or discomfort an inability to "escape" from a panic-proNausea or abdominal distress voking situation." Anticipatory anxiety is Feeling dizzy, unsteady, lightheaded or faint a hallmark of agoraphobia. In such cases, Derealization (feelings of unreality) or the mere anticipation of leaving the safety depersonalization (being detached from oneself) Fear of losing control or going crazy of home is enough to provoke a panic Fear of dying attack, so that even the thought of going Paresthesias (numbness or tingling sensations) out is avoided. Some persons with agoraChills or hot flushes phobia have no actual panic attacks, but the anticipatory rise in anxiety is enough *—Four of the symptoms listed are required for the to provoke the avoidance behavior. The diagnosis of panic attacks. intrusive thoughts, uncontrollable fears Adapted from American Psychiatric Association. and recurrent ruminations of persons with Diagnostic and statistical manual of mental disorders. panic disorder are similar to some of the 3d ed. rev. Washington, D.C: American Psychiatric abnormal thought patterns seen in obsesAssociation, 1987-237-8, and American Psychiatric Association. Diagnostic and statistical manual of men- sive-compulsive disorderly tal disorders, 4th ed. Washington, D.C: American Limited symptom attacks are of lower Psychiatric Association, 1994:395. severity and duration than the other forms of panic attacks and, by definition, are assoSpontaneous panic attacks arise without ciated with fewer than four of the listed warning or an identifiable trigger, and they usually are not preceded by heightened levels of anxiety. In contrast, situaTABLE 2 tional attacks arise from specific triggers or cues, and their occurrence is usually Additional Sjmiptoms Frequently predictable. Social phobias, fear of flying, Associated with Panic Attacks stage fright and fear of animals, insects or snakes fit into the category of situational Headache panic attacks. Some triggers may be more Diarrhea subtle and difficult to elucidate, such as Insomnia the fear of having an uncontrollable urge Chronic fatigue to urinate or defecate and not having an Coldness of hands Chronic feelings of fear or doom available restroom. This may lead to a Thoughts of suicide phobic avoidance of driving in heavy trafIntrusive thoughts and ruminations fic or riding public transportation, and it Alcohol or drug abuse may even result in agoraphobia. Situational attacks can occur as a result of NOTE: While common, these symptoms are not exposure to a specific trigger or in anticiincluded in the diagnostic criteria given in the pation of encountering it (anticipatory Diagnostic and Statistical Manual of Mental Disorders (DSM-IJI-R and DSM-IV). ).^'"'" A common thread in all TABLE 1

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volume 52, number 7


TABLE 3

Differential Diagnosis of Panic Disorder Coronary artery disease Cardiac arrhythmia Hypertension or hypotension Recurrent pulmonary emboli Asthma Transient ischemic attacks or cerebrovascular accidents Diabetes mellitus Hypoglycemia* Addison's disease Cushing's syndrome Carcinoid syndrome Hyperthyroidism Pheochromocytonia Severe anemia Labyrinthitis Meniere's disease Atypical migraine headaches Partial complex seizures Chronic fatigue syndrome* Drug use and abuse (especially amphetamines, diet pills, hydroxyzine, cocaine, caffeine, decongestants, levodopa, nicotine, lysergic acid diethylamide [LSD], theophylline, marijuana) Drug withdrawal (especially antihypertensive agents such as alpha blockers and beta blockers, alcohol, barbiturates, nicotine, benzodiazepines, tricyclic antidepressants) *—Common misdiagnosis.

symptoms.*"i° Patients who do not meet the criteria for panic disorder but have no other etiology for their symptoms may be having limited symptom attacks and should receive a trial of appropriate treatment. Epidemiology Panic disorder is a common problem encountered in primary care. It is as common as asthma and nearly three times more common than epilepsy. While the disorder has been reported to affect 1 to 3 percent of the general population,^-^^"*^ the actual prevalence may be even higher, because the diagnosis is easily missed by health care professionals and the condition is underreNovember 15,1995

ported by self-conscious patients.i*-^'' A recent study^" found that 119 (9 percent) of 1,266 subjects randomly selected from the general population met the criteria for panic attacks. Panic disorder tends to be familial. The first-degree relatives of patients with this disorder are 2.3 times more likely to be similarly affected than are persons in the general population.^ Whether the tendency of panic disorder to run in families is due to a learned response, an inherited predisposition or a combination of both factors remains a matter of debate. Panic disorder has a close association with depression, obsessive-compulsive disorder and generalized anxiety disorder. Secondary depression develops in as many as 70 percent of patients with panic disorder, while 20 percent of patients with a primary major depression report panic attacks.* Most patients with panic disorder that is not associated with any other major psychiatric illness also exhibit some symptoms of obsessive-compulsive disorder, such as unwanted intrusive thoughts, fearful imaginings and obsessional avoidance. In addition, patients with obsessive-compulsive disorder often experience varied levels of anxiety or panic if they attempt to resist their compulsions.*' Generalized anxiety disorder is a broad classification for patients with chronic anxiety. Their anxiety is often associated with symptoms of phobic avoidance and/or panic attacks. About 15 percent of patients with panic disorder abuse drugs or alcohol. Substance abuse may represent attempts at self-treatment of panic or anxiety symptoms.^ Presentation Patients with paruc disorder are typically passive-dependent, suspicious and distrustful of physicians and medications. Most, however, tend to seek medical help frequently and present with a myriad of seemingly unrelated somatic complaints. They also demonstrate diminished selfesteem and self-corifidence, show an exag2057


gerated sensitivity to criticism and tend to feel socially aUenated.^^-^^ Panic disorder patients require patience and understanding from their families and their physicians. TTiese patients commonly express fear of doctors and medications and often report previous bad experiences with medical treatment. Patients with panic disorder usually present with the complaint of episodes of mild to extreme generalized discomfort, and they describe sjmiptoms suggestive of cardiovascular, endocrinologic, pulmonary or neurologic disease {Tables 1 and 2). The frequent occurrence of these episodes while the patient is driving may be a clue that the symptoms may represent panic attacks. In all cases, panic attacks may occur occasionally to several times per day. During the patient's initial visit, it is of paramount importance for the physician to obtain a complete medical and family history and perform a thorough physical examination. Panic disorder is often a diagnosis of exclusion, and the differential diagnosis is extensive {Table 3). Many disorders can be ruled out based on the history, the physical examination and some conunon screening tests, such as a complete blood count, a fasting glucose or glucose tolerance test, thyroid function tests, serum electrolyte levels, an electrocardiogram, serum cortisol levels and pulmonary function tests (or even just a peak flow measurement). Treatment

In recent years, a number of useful treatment options for panic disorder have been developed. Apart from the lack of an accurate diagnosis, the most significant roadblocks to appropriate treatment for patients with panic disorder are their own fears and their resistance to the initiation of drug therapy. Almost universally, patients with this illness have a deep-seated, unrealistic fear that any medication will make them lose control. A large number of these patients also have an exaggerated sensitivity to many medications and previously have had unpleasant or frightening drug side 2058

effects. Thus, they can be excessively fearful of trying a new medication. Because of their fears and possible drug sensitivity, patients with panic disorder should be started on the lowest available dose of a medication, with the dosage increased as needed and tolerated. These patients also need frequent reassurance that the medication they are taking is safe and that it will not make them lose control. Once the drug regimen has been established, patients should be warned against stopping medications abruptly, since doing so may cause dangerous withdrawal symptoms and rebound anxiety. It may require several weeks or, rarely, months before especially fearful patients are vviUing to try a new medication. Pressuring such patients can be counterproductive because it can create a higher level of anxiety. Reassurance and patience seem to be the best course. Table 4 summarizes information on the drugs that are commonly used in the treatment of panic disorder. BENZODIAZEPINES

Benzodiazepines are the most effective drugs for the short-term treatment of panic disorder and panic attacks. The benzodiazepine alprazolam (Xanax) is presently the only drug with an indication for panic disorder with or without agoraphobia.^" The benzodiazepines can be classified as either high-potency or low-potency agents. The low-potency benzodiazepines were originally thought to be ineffective in panic disorder,^^ but several of these agents have been shown to be effective when used in equipotent doses (i.e., 50 mg of diazepam [Valium] = 5 mg of lorazepam [Ativan]). However, of the low-potency benzodiazepines, only diazepam has been studied extensively in the treatment of panic disorder.i-î"^3 Alprazolam is the high-potency benzodiazepine that has been most studied and most widely used in the treatment of panic disorder.i'î"^" The studies on alprazolam used a mean dosage of 5.6 mg per day,* but volume 52, number 7


TABLE 4

Drugs Commonly Used in the Treatment of Panic Disorder

Drug Low-potency benzodiazepines Diazepam (VaUum) Chlordiazepoxide (Librax) Clorazepate (Tranxene) Prazepam (Centrax) Oxazepam (Serax) High-potency benzodiazepines Alprazolam (Xanax) Clonazepam (BQonopin) Lorazepam (Ativan) Tricyclic antidepressants Clomipramine (Anafranil) Imipramine (Tofranil) Desipramine (Norpramin) Amitriptyline (Elavil, Endep) Nortriptyline (Pamelor) Selective serotonin reuptake inhibitors Eluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox) Beta blockers Propranolol (Inderal)l

Elimination half-life

Relative effectiveness in panic disorder

Rate of onset*

Therapeutic dosage range (mg/day)-\

20 to 50 hours 5 to 30 hours 36 to 200 hours 48 to 78 hours 5 to 10 hours

Good at high doses Fair to poort Fairt Fairi: Fairi:

Fast Slow Intermediate Slow Slow

2 to 40 10 to 40 7.5 to 60 20 to 60 40 to 120

12 to 15 hours 18 to 50 hours 12 hours

Excellent Good to excellent Good

Fast Fast Fast

0.75 to 8.0 Ito8 ltolO

19 to 37 hours§ 10 to 16 hours§ 13 to 23 hours§ 10 to 20 hours§ 18 to 43 hours

Excellent Good to excellent Good to excellent Good to excellent Good to excellent

1 to 3 weeks 1 to 3 weeks 1 to 3 weeks 1 to 3 weeks 1 to 3 weeks

25 to 250 25 to 250 10 to 250 10 to 250 10 to 150

2 to 3 daysll 26 hours 21 hours 16 hours

Excellent Possibly goodi: Excellent^ Excellent

Days to weeks Days to weeks Days to weeks Days to weeks

10 to 60 50 to 200 20 to 50 25 to 300

3 to 5 hours

Good

Fast

20 to 240

*—"Fast" indicates onset of action within 40 minutes, "intermediate" indicates onset of action within 40 minutes to two hours, and "slow" indicates onset of action within two to six hours. t—For each drug, the usual recommended dosage range is given; however, some patients require a higher or lower dosage. t—The effectiveness of this agent in panic disorder has not been well studied. §—The half-life of tricyclic antidepressants depends on the dose and is significantly longer at higher plasma levels. In addition, the half-life varies considerably from patient to patient. II—Norfluoxetine, the active metabolite offluoxetine, has a half-life of seven to nine days. 11—Other beta blockers may also be effective, but they have not been studied in the treatment of panic disorder.

the currently recommended dosages range from 2.0 to 8.0 mg per day in four to six divided doses. The drug can be initiated in a dosage as low as 0.25 mg three times daily, with the dosage increased as needed. Because of alprazolam's rapid onset (usually within 20 minutes), wide safety margin and low incidence of side effects, it is ideal for rapid abortion of a developing panic November 15,1995

attack, as well as for maintenance therapy. However, the drug's relatively short halflife (12 to 15 hours) makes frequent dosing necessary in most patients. Patients can become physically dependent on benzodiazepines after as little as two weeks of continuous use. Therefore, it is very important to taper any benzodiazepine slowly, because of the risk of 2059


Panic Disorder

rebound anxiety and withdrawal seizures. The dosage of alprazolam, for example, should be reduced by no more than 0.5 mg every four days; in some patients, the drug may need to be withdrawn at a rate as low as 0.25 mg every three or four days.^"-^^-^*^ If symptoms of panic or anxiety occur during tapering, the dosage should be held at that level or increased back to the previous level until the symptoms disappear. The last 1 to 2 mg are usually the most difficult to withdraw, and a tapering rate as low as 0.125 to 0.250 mg per week may be required. Clonazepam (Klonopin) is also effective in the treatment of panic disorder.* Like alprazolam, clonazepam should be given in a dosage ranging from 2 to 8 mg per day, although its longer half-life (18 to 50 hours) allows for less frequent dosing (three or four times per day) and makes withdrawal easier. One disadvantage of clonazepam is that its onset of action is not as rapid as alprazolam's. It should be recognized that clonazepam has no official indication for the treatment of panic disorder, although it is widely used in patients with this illness. Compared with alprazolam, lorazepam is slightly less effective in the treatment of panic disorder, and it may be associated with a greater tendency toward exacerbation of depression.^'' Lorazepam also has a longer onset of action and a shorter halflife (12 hours) than the other benzodiazepines used to treat panic disorder. It

The Author RAYMOND S. WEINSTEIN, M.D. practices family medicine in Dale City, Va., and he is affiliated with Potomac Hospital, Woodbridge, Va. He is also a clinical assistant professor of medicine at Georgetown University School of Medicine, Washington, D.C. Dr. Weinstein received his medical degree from the University of Washington School of Medicine, Seattle, and completed a residency in family medicine at Northridge (Calif.) Hospital. Address correspondence to Raymond S. Weinstein, M.D., Potomac Family Health of Dale City, 5800 Mapledale Plaza, Dale City, VA 22193.

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may also be more habituating and, thus, more difficult to withdraw. Recently, the potential for benzodiazepine dependence and abuse has become a concern. Although the potential for abuse of these drugs exists in a certain segment of the population, evidence suggests that patients with panic disorder do not develop an abusive-type pattern during long-term benzodiazepine therapy^'^-^^ and that they seem to have a better tolerance for higher dosages of these agents when doses are increased gradually^* Patients with debilitating symptoms of panic disorder should be given an adequate dose of the therapeutic agent, and the physidan must not be afraid to use whatever dosage is required to quell the symptoms. Once the dosage is stabilized, any required escalation may be suggestive of addiction and abuse, since tolerance to the anxiolytic effects of benzodiazepines is uncommon.^^-^' Experimental treatments of panic disorder include sublingual triazolam (Halcion) and intranasal midazolam (Versed). At present, however, the safety and effectiveness of these therapies are not established well enough to justify their use in patients with panic disorder. Buspirone (Buspar) has demonstrated little efficacy in patients with panic disorder.*^ TRICYCLIC ANTIDEPRESSANTS

Of the tricyclic antidepressants, imipramine (Tofrarul) has been the most widely studied, and it has been found to be highly effective in the treatment of both generalized anxiety disorder and panic disor(jgj. 1,4,30 Desipramine (Norpramin), nortriptyline (Pamelor) and amitriptyline (Elavil, Endep) have also been used with great success.* Nortriptyline maybe the preferred agent because of its lower incidence of anticholinergic side effects. Clomipramine (Anafranil), a newer tdcycUc antidepressant, is the only one with an indication for obsessive-compulsive disorder, and it may be the most effective drug in this class for the treatment of panic disorder.*-^*"** All tricyclic antidepressants should be started at their lowest dosage (10 to 25 mg volume 52, number 7


per day), and they may be given in divided doses or as a single dose at bedtime. The dosage can be increased by 10 to 25 mg every three or four days until a therapeutic response is achieved or unacceptable side effects occur. Ultimate daily dosages of 100 to 200 mg per day are not uncommon. The advantage of tricyclic antidepressants is their safety and the lack of habituation in long-term use. The main disadvantages are the slow onset of action of these drugs (one to three weeks) and the potential for side effects, even at low dosages. At the termination of treatment, all tricyclic antidepressants must be tapered over a period of two to six weeks, depending on the dosage. This class of drugs should be used with caution in patients with cardiovascular disease or a history of seizures. Tricyclic antidepressants may exacerbate bipolar (manic-depressive) illness. MONOAMINE OXIDASE INHIBITORS

Monoamine oxidase inhibitors (MAOIs) have been shown to be effective in the treatment of panic disorder.^^-^* However, their potential for dangerous interactions with many drugs and with foods containing tyramine, as well as the lifestyle changes their use requires, make MAOIs less desirable asfirst-linedrugs for patients with panic disorder. Once the restrictions and risks associated with MAOIs are explained, most pafients with panic disorder, who are already fearful and anxious at the prospect of trying medications, usually balk at taking a member of this drug class. New reversible inhibitors of monoamine oxidase are expected to become available in the near future. If these agents prove to be as beneficial as current MAOIs, they may become widely used in the treatment of panic disorder since their use does not require burdensome dietary restricfions. SELECTIVE SEROTONIN REUPTAKE INHIBITORS

Some selective serotonin reuptake inhibitors (SSRIs) have a parficularly beneficial effect in obsessive-compulsive disorder and panic disorder.^-'^-^^ Clomipramine, a November 15,1995

tricyclic anfidepressant, has strong serotonergic effects. Two SSRIs, fluoxefine (Prozac) and fiuvoxamine (Luvox), have proven to be highly effective in the treatment of panic disorder.^'^^'^^ Sertraline (Zoloft) may also have Umited benefits in obsessive-compulsive disorder and panic disorder.^^-^^ One recent study^ on paroxetine (Paxil) suggests that it is also effective in both obsessivecompulsive disorder and panic disorder. Of all the SSRIs available in the United States, fluoxetine has gained the greatest acceptance in panic disorder. It should be remembered that fluoxetine and its acfive metabolite norfluoxetine have extremely long half-lives (two to three days and seven to nine days, respectively); if side effects occur, these long half-Uves may be a disadvantage. Fluoxetine and norfluoxetine can also delay the metabolism of other drugs given concurrently or within weeks after the discontlnuafion of fiuoxetine, and they may cause up to a twofold increase in the plasma concentration of tricyclic anfidepressants. Even so, it is safe to caufiously augment fluoxetine with a tricyclic anfidepressant. In fact, patients who do not respond to either fluoxetine or clomipramine alone may respond well when both drugs are used concurrently Fluoxetine occasionally causes an increase in the already high anxiety levels of pafients with panic disorder. In such cases, the drug should be discontinued. A mild elevafion in anxiety may occur for the first several days of fluoxetine therapy; should this occur, no intervenfion beyond reassurance is required. BETA BLOCKERS

Propranolol (Inderal) is the only beta blocker that has been studied in panic disorder.^'^^ This agent has demonstrated at least some effectiveness in suppressing panic attacks, and it is very effective in diminishing many of the adrenergic-mediated symptoms of panic attacks associated with performance aruciety. Beta blockers are not appropriate firstline agents for the treatment of panic disor2061


der. If used in high doses or for periods of more than two weeks, these agents should be tapered to prevent a rebound effect. PSYCHOLOGIC THERAPIES

A number of psychologic therapies have been found to be as effective as drug therapy in patients with panic disorder. Behayior, cognitive, assertive, relaxation, mental imaging, desensitization and exposure therapies have all been extensively evaluated.^^ Cognitive therapy has proven to be the best modality for patients with panic and anxiety symptoms. Exposure therapy (exposure to phobic situations) is effective in patients with phobias but is less effective in those with panic, anxiety and depressive symptoms. A combination of cognitive, exposure and desensitization therapies has yielded the best results.^-^^ Psychologic therapy often produces beneficial effects that last long after treatment has been stopped.'-^^ Although drug therapy may also produce long-lasting benefits, this effect is not as consistent as in psychologic therapy; however, panic symptoms are relieved much more rapidly with medications. Concurrent drug therapy seems to facilitate psychologic therapy.'-^' DURATION OF TREATMENT

The duration of treatment depends on the patient, the frequency of the panic attacks and the severity of the anticipatory symptoms and avoidance behavior. Most patients require therapy for six months or longer.^' Occasionally, all attempts to discontinue treatment fail in a patient who is well controlled on medication, and symptoms reappear when medication is reduced. If such a patient has not undergone psychotherapy, this approach should be tried. Even with the best treatment, some patients require drug therapy indefinitely to lead a functional life. In most patients, continuous medication therapy is not required for more than one year. The farther away a patient is from the last panic attack, the greater the chance for 2062

a successful discontinuation of medication. A patient must be free from panic and avoidance for at least three months before withdrawal of medications is attempted. Only one drug should be discontinued at a time, starting with the benzodiazepine, which can be reserved for later occasional use as needed. In most patients, panic attacks are relieved completely during drug therapy, and 20 to 80 percent of patients do well following the discontinuation of medications.^ Some patients may have a relapse at some future time, but they usually respond to another course of therapy. With appropriate treatment, complete resolution of panic attacks is a reasonable and achievable goal. A patient information handout on panic attacks, panic disorder and agoraphobia is provided on page 2067.

REFERENCES . 1. Klerman G. Treatments for panic disorder. J Clin Psychiatry 1992;53(Suppl):14-9. 2. Rifkin A, Doddi S, Karajgi B, Hasan N, Alvarez L. Benzodiazepine use and abuse by patients at outpatient clinics. Am J Psychiatry 1989;146:1331-2. 3. Weissman MM, Klerman GL, Markowitz JS, Ouellette R. Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med 1989;321:1209-14. 4. Keller MB, Baker LA. The clinical course of panic disorder and depression. J Clin Psychiatry 1992;53(Suppl):5-8. 5. Fawcett J. Suicide risk factors in depressive disorders and in panic disorder. J Clin Psychiatry 1992;53(Suppl):9-13. 6. Fawcett J. Predictors of early suicide: identification and appropriate intervention. J Clin Psychiatry 1988;49(Suppl):7-8. 7. Dilsaver SC. Panic disorder. Am Fam Physician 1989;39(6):167-72. 8. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3d ed. rev. Washington, D.C: American Psychiatric Association, 1987:235-45. 9. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C: American Psychiatric Association, 1994:393-417. 10. Krystal JH, Woods SW, Hill CL, Charney DS. Characteristics of panic attack subtypes: assessment of spontaneous panic, situational panic, sleep panic, and limited symptom attacks. Compr Psychiatry 1991;32:474-80.

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11. Green MD. Living fear free: overcoming agorapho bia-the anxiety/panic syndrome. Dubuque, Iowa: KendaU/Hunt PubUshing, 1985. 12. Noyes R Jr, Reich JH, Suelzer M, Christiansen J. Personality traits associated with panic disorder: change associated with treatment. Compr Psychiatry 1991;32:283-94. 13. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD Jr, et al. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984;41:949-58. 14. Myers JK, Weissman MM, Tischler GL, Holzer GE 3d, Leaf PJ, Orvaschel H, et al. Six-month prevalence of psychiatric disorders in three communities 1980 to 1982. Arch Gen Psychiatry 1984;41:959-67. 15. Katon WJ, Von Korff M, Lin E. Panic disorder: relationship to high medical utilization. Am J Med 1992;92(Suppl 1A):7S-11S. 16. Goldstein A, Stainback B. Overcoming agoraphobia: conquering fear of the outside world. New York: Penguin Books, 1988, 17. Jenike MA, Baer L, Summergrad P, Minichiello WE, Holland A, Seymour R. Sertraline in obsessivecompulsive disorder: a double-blind comparison with placebo. Am J Psychiatry 1990;147:923-8 [Published erratum appears in Am J Psychiatry 1990;147:1393]. 18. Katerndahl DA, Realini JP. Where do panic attack sufferers seek care? J Fam Practice 1995;40(3):237-43. 19. Rapee RM, Sanderson WG, McGauley PA, Di Nardo PA. Differences in reported symptom profile between panic disorder and other DSM-III-R anxiety disorders. Behav Res Ther 1992;30:45-52. 20. Physicians' desk reference. 47th ed. Oradell, N,J,: Medical Economics Data, 1993:2589-93. 21. Mattick RP, Andrews G, Hadzi-Pavlovic D, Ghristensen H. Treatment of panic and agoraphobia. An integrative review. J Nerv Ment Dis 1990; 178:567-76. 22. Noyes R Jr, Anderson DJ, Glancy J, Growe RR, Slymen DJ, Ghoneim MM, et al. Diazepam and propranolol in panic disorder and agoraphobia. Arch Gen Psychiatry 1984;41:287-92. 23. Wilkinson G, Balestrieri M, Ruggeri M, Bellantuono G, Meta-analysis of double-blind placebo-controlled trials of antidepressants and benzodi-

November 15,1995

24.

25. 26.

27. 28. 29.

30.

31. 32.

33.

34.

35.

azepines for patients with panic disorders. Psychol Med 1991;21:991-8. Drug treatment of panic disorder. Gomparative efficacy of alprazolam, imipramine, and placebo. Gross-National Gollaborative Panic Study, Second Phase Investigators. Br J Psychiatry 1992;160:191202 [Published erratum appears in Br J Psychiatry 1992;161:724]. Ballenger JG. Medication discontinuation in panic disorder, J Glin Psychiatry 1992;53(Suppl):26-31. Noyes R Jr, Garvey MJ, Gook B, Suelzer M. Controlled discontinuation of benzodiazepine treatment for patients with panic disorder. Am J Psychiatry 1991;148:517-23, Chamey DS, Woods SW. Benzodiazepine treatment of panic disorder: a comparison of alprazolam and lorazepam, J Glin Psychiatry 1989;50:418-23. Shader RI, Greenblatt DJ. Use of benzodiazepines in anxiety disorders, N Engl J Med 1993;328:1398-405. Schweizer E, Rickels K, Weiss S, Zavodnick S, Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine. Arch Gen Psychiatry 1993;50:51-60. Gutler JL, Siris SG, "Panic-like" symptomatology in schizophrenic and schizoaffective patients with postpsychotic depression: observations and implications. Gompr Psychiatry 1991;32:465-73. Feinberg M. Glomipramine for obsessive-compulsive disorder. Am Fam Physician 1991;43:1735-8, Ghouinard G, Goodman W, Greist J, Jenike M, Rasmussen S, White K, et al. Results of a doubleblind placebo controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of obsessive-compulsive disorder. Psychopharmacol Bull 1990;26:279-84, Ghristiansen PE, Ohrberg S, Behnke K. Paroxetine effective in treating panic disorder. Proceedings of the 146th APA Annuat Meeting, San Francisco, 1993:1-3, Ravaris GL, Friedman MJ, Hauri PJ, McHugo GJ. A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients, J Glin Psychopharmacol 1991;ll:344-50. Shehi M, Patterson WM. Treatment of panic attacks with alprazolam and propranolol. Am J Psychiatry 1984;141:900-l,

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