5kato_cp.indd

T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. A 30-year-old woman, recently divorced, presents with daily episodes of chest pain,
shortness of breath, sweating, and palpitations. She feels very anxious when these
episodes occur and worries that she may be having a heart attack. She reports increas-
ing avoidance of social activities, moodiness, poor sleep, and a low level of energy.
She takes no medications and reports no drug or alcohol use. Her physical examina-
tion is normal. How should this case be managed?
From the Department of Psychiatry and Panic disorder occurred in approximately 1 to 3 percent of respondents to a commu-Behavioral Sciences, University of Wash- nity survey1 and in 3 to 8 percent of patients seen by primary care physicians.2-4 The ington, Seattle. Address reprint requests to Dr. Katon at the Department of Psychia- disorder is twice as common among women as among men, and there appears to try and Behavioral Sciences, Box 356560, be a bimodal distribution in the age at onset, with one peak in late adolescence and University of Washington School of Med- a second peak in the mid-30s.5,6 Patients who have panic disorder in adolescence icine, 1959 N.E. Pacific St., Seattle, WA 98195-6560, or at [email protected]. frequently have depressive episodes or coexisting depression and anxiety in their edu.
Diagnosis
Copyright 2006 Massachusetts Medical Society. Table 1 lists the criteria for a diagnosis of panic disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition.6 These criteria require recurrent attacks of anxiety that build to a peak within seconds or minutes and a change in behavior such as avoidance of social activities, worry about having subsequent attacks, or concern about losing one’s mind.6 The worry in patients with panic dis-order about recurrence of attacks or about the implication of attacks should be differentiated from the six months or more of worry about many other life issues required for the diagnosis of generalized anxiety disorder.
Risk Factors and Precipitants
There are both biologic and environmental causes of panic disorder. Monozygotic twins have a significantly higher concordance rate for the disorder than do dizygotic twins.8 The risk of panic disorder is increased by a factor of eight in first-degree relatives of patients with the disorder.9 Panic disorder may result from an abnormally sensitive fear network, which includes the prefrontal cortex, insula, thalamus, amygdala and projections from the amygdala to the locus ceruleus, hypothalamus, periaqueductal gray substance, and parabrachial nucleus.10 Approximately 80 percent of patients with panic disorder report major life stressors during the previous 12 months.11,12 Patients with a history of sexual or physical abuse in childhood have a higher risk of panic disorder as adults than those without this history,13 as do teenagers who smoke, as compared with those who do not smoke.14 Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. As many as 90 percent of patients with panic Table 1. Criteria for a Diagnosis of Panic Disorder.*
disorder will have at least one other psychiatric disorder during their lifetime.1,5 Conditions report- Recurrent unexpected panic attack, defined as a discrete period of intense ed more commonly among community-based– fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: survey respondents with panic disorder than in the general population include major depression, generalized anxiety disorder, agoraphobia, post- Trembling or shakingShortness of breath or choking traumatic stress disorder, bipolar disorder, and alcohol abuse.1,5,15 In many patients, fears and avoidance of social situations develop after the Nausea or abdominal distressFeeling dizzy, light-headed, or faint development of panic disorder, along with a high associated risk of agoraphobia. Some,16,17 but not all,18 studies have shown an increased risk of suicidal ideation and suicide attempts in patients with panic disorder, even after adjustment for de- At least one of the attacks followed by one month (or more) of one (or more) pression. The risk of suicidal behavior is likely to be increased among patients with panic disorder Persistent concern about having additional attacks Worry about the implications of the attack or its consequences A clinically significant change in behavior related to the attacks The frightening physical symptoms of panic Panic attacks not due to the direct physiological effects of an illicit substance disorder often lead to extensive use of medical (or a prescribed medication) or a general medical condition (e.g., hy- services.19 Patients with medically unexplained syndromes such as irritable bowel syndrome,20 Panic attacks not better accounted for by another mental disorder, such as chest pain with negative results on cardiac test- social phobia (on exposure to a feared social situation), a specific phobia ing,21 palpitations,22 interstitial cystitis,23 and (during exposure to a specific situation that prompts a phobic response), post-traumatic stress disorder (in response to stimuli associated with chronic fatigue syndrome24 have been shown to a severe stressor), or separation anxiety disorder (in response to being have higher rates of coexisting panic disorder than do control subjects with documented med-ical syndromes. The frequency of panic disorder * The criteria are from the Diagnostic and Statistical Manual of Mental Disorders, is also higher among patients with asthma and other chronic respiratory disorders,25 mitral-valve prolapse,26 labile hypertension with negative re- tions are as follows: In the past six months, did sults on testing for pheochromocytoma,27 and you ever have a spell or attack when all of a sud-migraine headache28 than among those without den you felt frightened, anxious, or very uneasy? these conditions.
In the past six months, did you ever have a spell Panic disorder is usually a relapsing–remitting or attack when for no reason your heart suddenly disorder, although approximately 20 percent of began to race, you felt faint, or you couldn’t catch patients have a chronic course.29 Coexisting ma- your breath? Another screening tool, the Patient jor depression, agoraphobia, and personality dis- Health Questionnaire, also includes screening order, however, are predictive of more persistent questions for panic disorder (provided in the Sup-panic attacks and symptoms of anxiety.30 plementary Appendix, available with the full text of this article at www.nejm.org).32 This instru- S t r a t e g i e s a n d E v i d e n c e ment is reported to have a high sensitivity (81 per-cent; 95 percent confidence interval, 69 to 93 Screening
percent) and specificity (99 percent; 95 percent Screening for panic disorder is not routinely rec- confidence interval, 98 to 100 percent) for a diag-
ommended but may be helpful in groups at high nosis of panic disorder (as confirmed on an inter-
risk, such as heavy users of medical services and view by a mental health professional).33
those with unexplained symptoms.19-24,31 A two-
item screening questionnaire has been shown to Evaluation
have a high sensitivity (range, 94 to 100 percent) A careful history taking and physical examination
but low specificity (range, 25 to 59 percent) in are warranted for all patients to rule out medical
three primary care populations.32 The two ques- causes of symptoms. Conditions and agents that
Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e can mimic or cause panic attacks include hyper- pines in treating depression was marginally less thyroidism and hypothyroidism, temporal-lobe that that of either tricyclic antidepressants or epilepsy, asthma, cardiac arrhythmias, pheochro- SSRIs.34 Large studies have shown a clinically mocytoma, excessive intake of caffeine or other significant response (defined by a 50 percent de-stimulants, withdrawal from alcohol, and treat- crease in the frequency of panic attacks or global ment with high doses of corticosteroids.33 Chem- anxiety) in 50 to 80 percent of patients treated istry panels, measurement of thyrotropin levels, with SSRIs, tricyclic antidepressants, or benzodi-and electrocardiography are often ordered to iden- azepines.34tify underlying medical causes, but these tests usu- An earlier meta-analysis compared the effects ally have negative results in the absence of other of SSRIs or placebo in 12 randomized, controlled evidence suggesting medical causes. Screening for trials.36 SSRIs were significantly more effective depression33 is important, given the increased than placebo in reducing global anxiety and the prevalence of depression among patients with frequency of panic attacks; more than 50 percent panic disorder and the associated risk of suicidal of patients treated with SSRIs became panic-free behavior.
in seven of nine studies reporting this outcome. Another earlier meta-analysis found that tricyclic Education of Patients
antidepressants were more effective than placebo An essential step after the clinical diagnosis is in nine studies in reducing global anxiety and made is to review with the patient her or his fears the mean frequency of panic attacks and that of medical illness and expectations of medical benzodiazepines were more effective than place-testing and treatment. More than 80 percent of bo in treating global anxiety (in 13 studies) and patients with panic disorder present with a med- the frequency of panic attacks (in 7 studies).37 In ical symptom, and most are fearful of having a the seven studies that reported whether patients serious condition, such as a heart attack.31 Clini- were panic-free at study completion, the rate of cal experience suggests that patients benefit from freedom from panic attacks was 61 percent for education about panic disorder as the cause of benzodiazepines and 58 percent for tricyclic their symptoms and the mechanism by which a agents.37brain disorder may provoke physical symptoms. In a recent large, placebo-controlled trial in Educational materials for patients may be ob- patients with panic disorder, the SNRI venlafax-tained from the Anxiety Disorders Association ine (Effexor, Wyeth-Ayerst), at a dose of 75 to of America (www.adaa.org) and the National 225 mg per day, reduced the global severity of Institute of Mental Health (www.nimh.nih.gov/ panic, anticipatory anxiety, and fear and avoidance healthinformation/anxietymenu.cfm).
of social activities on the basis of validated anxi-ety scales. However, the drug did not increase the Pharmacologic Management
Five classes of medication have been shown in Because of their safety profile, as compared randomized trials to be more effective than pla- with the safety profiles of tricyclic agents and cebo in patients with panic disorder: selective monoamine oxidase inhibitors, SSRIs are recom-serotonin-reuptake inhibitors (SSRIs), serotonin- mended as the first drug option in the treatment norepinephrine reuptake inhibitors (SNRIs), high- of panic disorder.36,38 The side effects of SSRIs potency benzodiazepines, tricyclic antidepressants, (Table 2) tend to occur early in treatment, before and monoamine oxidase inhibitors.34-40 A recent the therapeutic effects. Because clinical experi-meta-analysis compared the efficacy of three ence suggests that many patients with panic dis-pharmacologic classes of medications with place- order are hypervigilant regarding side effects, bo in patients with panic disorder as measured by SSRIs should be started at low doses, with dose levels of global anxiety (frequency of panic at- titration every five to seven days, as tolerated. tacks, and agoraphobia) and depression: SSRIs The goal of treatment should be to eliminate (in 17 trials), tricyclic antidepressants (in 23 tri- panic attacks, if possible, because a partial re-als), and benzodiazepines (in 25 trials).34 The sponse often results in continued avoidance of three classes of medication were equally effective frightening situations and impairment in social in treating anxiety, but the effect of benzodiaze- functioning. After the patient is free of panic, Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. Table 2. Pharmacologic Treatment for Panic Disorder.*
Medication
Starting Dose
Therapeutic Dose
Half-Life
Side Effects
Selective SSRIs
Class effects include nausea, anorexia, tremors, anxiety, sexual dysfunction, jitteriness, insomnia Class effects and drowsiness, fatigue, weight gain Tricyclic antidepressants‡
Class effects include sedation, weight gain, dry mouth, urinary hesitancy, constipation, orthostatic hypoten-sion, and slow conduction time through the His bundle Benzodiazepines§
Class effects include sedation, cognitive slowing, physical Class effects include nausea, sweating, dry mouth, dizziness, insomnia, somnolence, sexual dysfunction, and hyper- * Clonazepam and all SSRIs, except paroxetine, are in Food and Drug Administration (FDA) pregnancy category C. Paroxetine is in category D, as are all tricyclic antidepressants, lorazepam, and alprazolam. Category C drugs include those for which “either studies in animals re-vealed adverse effects on the fetus and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.” Category D drugs include those for which “there is posi-tive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is need-ed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).” † This drug was approved by the FDA for the treatment of panic disorder.
‡ Baseline electrocardiography is recommended (tricyclic antidepressants are contraindicated for patients with conduction abnormalities).
§ These agents could be used as needed to help patients confront feared situations. A 0.5-mg dose of oral clonazepam, alprazolam, or loraze- pam or a 0.5-mg dose of sublingual lorazepam is recommended.
Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e the clinician should encourage her or him to re- four to eight weeks is recommended. Switching encounter feared situations to increase confidence to a benzodiazepine with a longer half-life may in abilities and participation in social activities.
facilitate tapering of the dose.39 Generally, patients Although rigorous data are lacking to guide who have a history of substance abuse, personal- the care of patients who do not have a response ity disorder, or chronic pain should not be treated to initial SSRI therapy, clinical experience sug- with benzodiazepines because of the high risk of gests that it is reasonable to try an alternative overuse of these medications. Those with moder-SSRI. If there is still no response, switching to ate-to-severe major depression and panic should another class of drug — tricyclic antidepressant, initially be treated with antidepressants (either benzodiazepine, or SNRI — is recommended.38 alone or in combination with other medica- Although the benzodiazepines continue to tions).38 have an important role in the treatment of panic
disorder, concern with respect to dependence, Nonpharmacologic Management
medication abuse, side effects, and the rapid re- Cognitive behavioral treatment is provided in 12
emergence of symptoms after discontinuation to 16 sessions over a period of three to four
have led to the recommendation that these agents months and is focused on recreating the feared
should not be the first choice for treatment.39 symptoms and then modifying the patient’s usual
When benzodiazepines are used in combination responses to the symptoms.42 If a feared symp-
with antidepressants, there is a more rapid treat- tom is rapid heart rate, for example, the mental
ment response than with antidepressants alone.40 health professional or physician may have the pa-
In a trial comparing sertraline (Zoloft, Pfizer) and tient jog in place until the symptoms are pro-
placebo with sertraline and clonazepam (Klono- voked. The mental health professional or physi-
pin, Roche) (at a dose of 0.5 mg three times a day), cian helps the patient correct cognitive distortions
the clonazepam group had a significantly higher such as exaggerating the threat to health (e.g.,
rate of response (defined by a decrease in symp- having thoughts such as “I am going to die”) that
toms of 50 percent or more) than the group re- precipitate more anxiety. Finally, the mental health
ceiving sertraline and placebo at week 1 (41 per- professional or physician helps the patient mod-
cent vs. 4 percent) and week 3 (63 percent vs. 32 ify the associated behaviors, such as seeking es-
percent), but not at later points of assessment.40 cape and avoidance.
Benzodiazepines can also be added to antidepres-
A recent meta-analysis of 11 randomized clini- sants to counteract patients’ early jitteriness and cal trials comparing the use of cognitive behav-agitation or to augment antidepressants in those ioral treatment and antidepressants (SSRIs or tricy-who have a partial response to treatment.39 Benzo- clic antidepressants) showed that these treatments diazepines with longer half-lives (such as extended- had similar effects on global anxiety, clinical re-release alprazolam [Xanax XR, Pharmacia and sponse (defined by a decrease in symptoms of 50 Upjohn] and clonazepam) are often preferred in percent or more), and depression.34 The largest of order to reduce breakthrough anxiety. Benzodi- these trials compared cognitive behavioral treat-azepines are frequently used “as needed,” to per- ment (initially weekly) alone, an antidepressant mit confrontation with feared stimuli (e.g., air (imipramine [Tofranil, Mallinckrodt]) alone, cog-travel). Infrequent as-needed use, such as three nitive behavioral treatment plus imipramine, and times a month, is not a matter of concern, but cognitive behavioral treatment plus placebo with more frequent use may lead to fluctuating serum placebo alone in a study of 312 patients with levels and withdrawal symptoms.39 panic disorder uncomplicated by depression or A disadvantage of the benzodiazepines is that agoraphobia.43 After three months, response rates as many as 40 to 80 percent of patients treated (defined by a decrease in symptoms of 40 percent with them for longer than four months may have or more, according to a global panic measure) a discontinuation syndrome, characterized by anx- were significantly greater for all active treatments iety, irritability, headache, muscle tension, percep- than for placebo: 49 percent with cognitive be-tual abnormalities, insomnia, decreased concen- havioral treatment alone, 46 percent with imipra-tration, and cardiorespiratory symptoms upon mine alone, 60 percent with cognitive behavioral stopping the medication.41 A slow tapering over treatment and imipramine, and 57 percent with Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. cognitive behavioral treatment and placebo (vs. ment that was previously successful. For patients 22 percent with placebo). There were no signifi- who have two or more relapses, long-term use of cant differences between the group receiving medication may be necessary.38imipramine alone and the group receiving cog-nitive behavioral treatment alone.
Patients with a response at three months en- tered a six-month maintenance phase of monthly The clinical practice guidelines for the treatment appointments; at nine months, response rates for of panic disorder of both the American Psychiat-all groups receiving active treatment remained ric Association38 and the Royal Australian College better than for placebo: 40 percent in the group of Psychiatrists46 recommend that the severity of receiving cognitive behavioral treatment alone, symptoms, patients’ preferences, the response to 38 percent in the group receiving imipramine treatment during prior episodes, and the avail-alone, 57 percent in the group receiving cogni- ability of a clinician with experience with cogni-tive behavioral treatment and imipramine, and tive behavioral treatment should influence the 47 percent in the group receiving cognitive behav- treatment recommendations, since medications ioral treatment and placebo, as compared with and cognitive behavioral treatment are equally ef-13 percent in the placebo group. Response rates fective. When medications are used, both of the for cognitive behavioral treatment at nine months guidelines recommend initiating SSRIs as the first were similar to that (54 percent) reported in a line of treatment on the basis of their better side-meta-analysis of 14 studies.44 The combination effect profile and safety than tricyclic antidepres-of cognitive behavioral treatment and imipramine sants and benzodiazepines and given the more was more effective than cognitive behavioral treat- limited data on the efficacy of SNRIs.
ment alone or imipramine alone but not signifi-cantly more effective than cognitive behavioral A meta-analysis of 20 studies comparing cog- The optimal length of prophylactic pharmaco- nitive behavioral treatment and antidepressant therapy after a response to short-term treatment medication with cognitive behavioral treatment is unclear. There are limited data regarding the alone likewise suggested that the combination role of cognitive behavioral treatment in patients was more effective in reducing global anxiety and with a partial response or no response to pharma-depression than either therapy alone.34 However, cotherapy, and vice versa. There are also limited this meta-analysis found that both approaches data on the optimal choice of a next medication were similarly effective during long-term follow- if the first one proves to be ineffective. More up after treatment had ended.
studies are needed to confirm whether cognitive Some improvement is expected within 2 to behavioral treatment, as compared with pharma- 4 weeks with medication and within 4 to 8 weeks cotherapy, may be associated with a lower risk of with cognitive behavioral therapy, although a full relapse.34,43response to either therapy may take 8 to 12 weeks. Strategies are needed to enhance the provision If there is no improvement within six to eight of effective care to people in the general popula-weeks, reconsideration of the diagnosis is war- tion who have panic disorder, since only a minor-ranted. The clinician should also consider the ity of those with this disorder receive any mental need for a different treatment or for combined health treatment. In two trials, the integration cognitive behavioral treatment and medication. of mental health professionals into primary care When treatment with medication is effective, dis- to help in the provision of pharmacotherapy, cog-continuation should be considered after 12 months, nitive behavioral treatment, or both in patients although data are lacking to guide the optimal with panic disorder was associated with a reduc-duration of therapy. Close follow-up is warrant- tion in the levels of anxiety and total health care ed, because as many as one third of patients will costs, as compared with usual primary care.47,48 have a relapse within two years after treatment In the first trial, psychiatrists consulted with pa-has ended.45 If the patient has a relapse, it is tients for approximately two visits to assist the reasonable to start another course of the treat- primary care physician with pharmacologic man- Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e agement of the disorder. In the second trial, tween them should be based on the patient’s pref-mental health professionals were integrated into erence and the availability of competent cognitive the primary care to provide cognitive behavioral behavioral therapists. SSRIs should be the first treatment and aid pharmacologic management line of pharmacologic treatment for patients with on the basis of recommendations of the super- panic disorder. If side effects such as jitteriness vising psychiatrists.47,48 arise, adjunctive short-term treatment with a ben-zodiazepine may be helpful. One year of treat- S u m m a r y a n d R e c o m m e n d a t i o n s ment is generally recommended after an initial response. If bothersome side effects persist, tricy- The patient in the vignette has symptoms typical clic antidepressants, an SNRI, or benzodiazepines of panic disorder associated with increasing avoid- may be used, since all have also been proven to ance of social activities and associated depressive be effective in the treatment of panic disorder in symptoms. Either pharmacologic therapy or cog- randomized clinical trials.
nitive behavioral treatment is a reasonable initial Dr. Katon reports having received consulting fees from Eli Lilly, Wyeth, and GlaxoSmithKline and lecture fees from Forest and approach, because the two therapies are equally Eli Lilly. No other potential conflict of interest relevant to this effective in controlling symptoms. The choice be- article was reported.
Refe renc e s
1. Kessler RC, McGonagle KA, Zhao S, 11. Roy-Byrne PP, Geraci M, Uhde TW. in patients with irritable bowel syndrome
et al. Lifetime and 12-month prevalence Life events and the onset of panic disor-
of DSM-III-R psychiatric disorders in the der. Am J Psychiatry 1986;143:1424-7.
United States: results from the National 12. Manfro GG, Otto MW, McArdle ET, 21. Katon W, Hall ML, Russo J, et al.
Comorbidity Survey. Arch Gen Psychiatry Worthington JJ III, Rosenbaum JF, Pollack
Chest pain: relationship of psychiatric ill- MH. Relationship of antecedent stressful ness to coronary arteriographic results. 2. Spitzer RL, Kroenke K, Linzer M, et al. life events to childhood and family his-
Health-related quality of life in primary tory of anxiety and the course of panic 22. Barsky AJ, Cleary PD, Coeytaux RR,
care patients with mental disorders: re-
disorder. J Affect Disord 1996;41:135-9.
Ruskin JN. Psychiatric disorders in medi- sults from the PRIME-MD 1000 Study. 13. Kendler KS, Bulik CM, Silberg J, Hette-
ma JM, Myers J, Prescott CA. Childhood tions. J Gen Intern Med 1994;9:306-13.
3. Leon AC, Olfson M, Broadhead WE, sexual abuse and adult psychiatric and 23. Weissman MM, Gross R, Fyer A, et al.
et al. Prevalence of mental disorders in substance use disorders in women: an epi-
Interstitial cystitis and panic disorder: primary care: implications for screening. demiological and cotwin control analysis. 4. Roy-Byrne P, Katon W, Broadhead WE, 14. Breslau N, Klein DF. Smoking and 24. Katon WJ, Buchwald DS, Simon GE,
et al. Subsyndromal (“mixed”) anxiety — panic attacks: an epidemiologic investiga-
Russo JE, Mease PJ. Psychiatric illness in depression in primary care. J Gen Intern tion. Arch Gen Psychiatry 1999;56:1141-7.
15. Hettema JM, Prescott CA, Myers JM, with rheumatoid arthritis. J Gen Intern
5. Weissman MM, Bland RC, Canino GJ, Neale MC, Kendler KS. The structure of Med 1991;6:277-85.
et al. The cross-national epidemiology of genetic and environmental risk factors for
25. Katon WJ, Richardson L, Lozano P,
panic disorder. Arch Gen Psychiatry 1997; anxiety disorders in men and women. McCauley E. The relationship of asthma 6. Diagnostic and statistical manual of 16. Pilowsky DJ, Olfson M, Gameroff MJ, 2004;66:349-55.
mental disorders. 4th ed. rev.: DSM-IV-R. et al. Panic disorder and suicidal ideation 26. Margraf J, Ehlers A, Roth WT. Mitral
Washington, D.C.: American Psychiatric in primary care. Depress Anxiety 2006;23:
valve prolapse and panic disorder: a review of their relationship. Psychosom Med 1988; 7. Merikangas KR, Zhang H, Avenevoli S, 17. Sareen J, Cox BJ, Afifi TO, et al. Anxi-
Acharyya S, Neuenschwander M, Angst J. ety disorders and risk for suicidal ideation 27. Fogarty J, Engel C, Russo J, Simon G,
Longitudinal trajectories of depression and suicide attempts: a population-based Katon W. Hypertension and pheochromo-and anxiety in a prospective community longitudinal study of adults. Arch Gen cytoma testing: the association with anxi-study: the Zurich Cohort Study. Arch Gen Psychiatry 2005;62:1249-57.
ety disorders. Arch Fam Med 1994;3:55-60.
18. Vickers K, McNally RJ. Panic disorder 28. Stewart WF, Linet MS, Celentano DD.
8. Torgersen S. Genetic factors in anxi-
ety disorders. Arch Gen Psychiatry 1983; morbidity Survey. J Abnorm Psychol 2004; Psychosom Med 1989;51:559-69.
40:1085-9.
29. Keller MB, Hanks DL. Course and out-
9. Crowe RR, Noyes R, Pauls DL, Slymen 19. Simon GE. Psychiatric disorder and come in panic disorder. Prog Neuropsy-
D. A family study of panic disorder. Arch functional somatic symptoms as predic-
tors of health care use. Psychiatr Med 551-70.
10. Gorman JM, Kent JM, Sullivan GM, 1992;10:49-59.
30. Bruce SE, Yonkers KA, Otto MW, et al.
Coplan JD. Neuroanatomical hypothesis of 20. Walker EA, Gelfand AN, Gelfand MD, Inf luence of psychiatric comorbidity on
panic disorder, revised. Am J Psychiatry Katon WJ. Psychiatric diagnoses, sexual recovery and recurrence in generalized 2000;157:493-505.
and physical victimization, and disability anxiety disorder, social phobia, and panic Downloaded from www.nejm.org at HLTH SCIENCE INFO CONSORTIUM O on July 3, 2006 . Copyright 2006 Massachusetts Medical Society. All rights reserved. disorder: a 12-year prospective study. Am 37. Gould RA, Otto MW, Pollack MH. 44. Westen D, Morrison K. A multidimen-
J Psychiatry 2005;162:1179-87.
A meta-analysis of treatment outcome for sional meta-analysis of treatments for de- 31. Katon W. Panic disorder in the medi-
panic disorder. Clin Psychol Rev 1995;15: pression, panic, and generalized anxiety cal setting. Washington, D.C.: National 819-44.
disorders: an empirical examination of the Institute of Mental Health, 1994. (NIH 38. Working Group on Panic Disorder. status of empirically supported therapies.
publication no. 94-3482.)
Practice guideline for the treatment of pa- J Consult Clin Psychol 2001;69:875-99.
32. Stein MB, Roy-Byrne PP, McQuaid JR, tients with panic disorder. Am J Psychia-
45. Yonkers KA, Bruce SE, Dyck IR, Keller
et al. Development of a brief diagnostic try 1998;155:Suppl:1-34.
MB. Chronicity, relapse, and illness — screen for panic disorder in primary care. 39. Susman J, Klee B. The role of high-
course of panic disorder, social phobia, potency benzodiazepines in the treatment and generalized anxiety disorder: findings 33. Spitzer RL, Kroenke K, Williams JB. of panic disorder. Prim Care Companion J in men and women from 8 years of fol-
Validation and utility of a self-report ver-
low-up. Depress Anxiety 2003;17:173-9.
sion of PRIME-MD: the PHQ primary care 40. Goddard AW, Brouette T, Almai A, 46. Royal Australian and New Zealand
study: Primary Care Evaluation of Mental Jetty P, Woods SW, Charney D. Early co-
College of Psychiatrists Clinical Practice Disorders: Patient Health Questionnaire. administration of clonazepam with sertra- line for panic disorder. Arch Gen Psychia- 34. Mitte K. A meta-analysis of the effi-
clinical practice guidelines for the treat- cacy of psycho- and pharmacotherapy in 41. Benzodiazepine dependence, toxicity ment of panic disorder and agoraphobia.
panic disorder with and without agora-
and abuse: a task force report of the Amer- Aust N Z J Psychiatry 2003;37:641-56.
phobia. J Affect Disord 2005;88:27-45.
ican Psychiatric Association. Washington, 47. Katon WJ, Roy-Byrne P, Russo J, Cow-
35. Bradwejn J, Ahokas A, Stein DJ, Sali-
D.C.: American Psychiatric Association, ley D. Cost-effectiveness and cost offset of nas E, Emilien G, Whitaker T. Venlafaxine a collaborative care intervention for pri- extended-release capsules in panic disor- 42. Landon TM, Barlow DH. Cognitive-
der: flexible-dose, double-blind, placebo- behavioral treatment for panic disorder: Arch Gen Psychiatry 2002;59:1098-104.
controlled study. Br J Psychiatry 2005;187: current status. J Psychiatr Pract 2004;10: 48. Katon W, Russo J, Sherbourne C, et al.
352-9.
Incremental cost-effectiveness of a collab- 36. Otto MW, Tuby KS, Gould RA, McLean
43. Barlow DH, Gorman JM, Shear MK, orative care intervention for panic disor-
RY, Pollack MH. An effect-size analysis of Woods SW. Cognitive-behavioral therapy, der. Psychol Med 2006;36:353-63.
the relative efficacy and tolerability of se- imipramine, or their combination for pan- Copyright 2006 Massachusetts Medical Society. rotonin selective reuptake inhibitors for ic disorder: a randomized controlled trial. panic disorder. Am J Psychiatry 2001;158: JAMA 2000;283:2529-36. [Errata, JAMA 1989-92.
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