AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks, the frequency of which can vary from several attacks a day to only a few attacks a year.

To meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for panic disorder, panic attacks must be associated with more than 1 month of subsequent persistent worry about (1) having another attack, (2) consequences of the attack, or (3) significant behavioral changes related to the attack.

Panic attacks are a period of intense fear in which 4 of 13 defined symptoms develop abruptly and peak rapidly less than 10 minutes from symptom onset. To make the diagnosis of panic disorder, panic attacks cannot directly or physiologically result from substance use, medical conditions, or another psychiatric disorder.

The DSM-IV-TR delineates the following potential symptom manifestations of a panic attack:

• Palpitations, pounding heart, or accelerated heart rate
• Sweating
• Trembling or shaking
• Sense of shortness of breath or smothering
• Feeling of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Feeling dizzy, unsteady, lightheaded, or faint
• Derealization or depersonalization (feeling detached from oneself)
• Fear of losing control or going crazy
• Fear of dying
• Numbness or tingling sensations
• Chills or hot flashes

Panic disorder is usually qualified with the presence or absence of agoraphobia. Agoraphobia is defined as anxiety toward places or situations in which escape may be difficult or embarrassing. These anxiety-provoking situations are avoided or are endured with anxiety. (Note: Agoraphobia is not a stand-alone disorder; it is a descriptive term [eg, panic disorder with agoraphobia.])

Pathophysiology

Several non–mutually exclusive theories have been proposed to explain panic disorder, particularly from a biologic perspective, in response to the observed efficacy of certain pharmacologic agents for controlling the symptoms.

• The serotonergic model suggests an exaggerated postsynaptic receptor response to synaptic serotonin. Recent studies report subsensitivity of 5HT1A receptors. The 5HT system or one of its subsystems may play a role in the pathophysiology of panic disorder, the precise nature of which must be delineated by further investigation.
• The catecholamine model postulates increased sensitivity to adrenergic CNS discharges, with hypersensitivity of presynaptic alpha-2 receptors.
• Similarly, the locus ceruleus model explains that panic symptoms are due to increased local discharge resulting in adrenergic neuron stimulation, similar to the more general catecholamine theory. Locus ceruleus activity also affects the hypothalamic-pituitary-adrenal axis, which can respond abnormally to clonidine in patients with panic disorder.
• The lactate model focuses on symptom production by postulated aberrant metabolic activity induced by lactate.
• The false suffocation carbon dioxide hypothesis explains panic phenomena by hypersensitive brainstem receptors.
• The GABA model postulates decreased inhibitory receptor sensitivity, with a resultant excitatory effect.
• The neuroanatomic model suggests that panic attacks are mediated by a "fear network" in the brain that involves the amygdala, the hypothalamus, and the brainstem centers.
• The genetic hypothesis has attempted to refer panic disorder to definable genetic loci, without success to date.

Frequency

United States

Lifetime prevalence estimates range from 1.5-5% for panic disorder and 3-5.6% for panic attacks.

Mortality/Morbidity

Significant comorbidities are associated with panic disorder.

• Panic disorder often coexists with mood disorders, with mood symptoms potentially following the onset of panic attacks. Lifetime prevalence rates of major depression may be as much as 50-60%. These patients may be at higher risk of suicide attempts. Alcohol and other substance use disorders are also frequent sequelae of panic disorder.
• Medical conditions apparently share significant comorbidity with panic disorder. These conditions include cardiovascular disorders (eg, mitral valve prolapse, hypertension, cardiomyopathy) and other disorders (eg, chronic obstructive pulmonary disorder, irritable bowel syndrome, migraine headache).
• Aside from the significant psychological anguish of panic attacks, agoraphobia can result in numerous medical, social, and occupational consequences. These include increased health care use, social withdrawal and restricted role functioning, and decreased work productivity.

Race

Data on prevalence in different racial groups are inconsistent. Symptom manifestations may differ, with African Americans more often presenting with somatic symptoms and more likely seeking help in medical rather than psychiatric settings.

Sex

One-month prevalence estimates for women are 0.7% versus 0.3% for men (ie, women are more likely to be affected than men by a 2- to 3-fold factor).

Age

Panic disorder has a bimodal distribution, with highest incidence in late adolescence and a second peak in the mid 30s.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

A sudden onset of a panic attack reportedly occurs with 4 (or more) of the 13 associated symptoms progressing to a peak within 10 minutes. Triggers and patterns help construct the differential diagnosis.

• Unexpected panic attacks have no known precipitating cue; these panic attacks often support the diagnosis of panic disorder without agoraphobia.
• Situationally bound (cued) panic attacks recur predictably in temporal relationship to the trigger; these panic attacks usually implicate a specific phobia-type diagnosis.
• Situationally predisposed panic attacks are more likely to occur in relation to a given trigger, but they do not always occur. This pattern more likely describes panic disorder with agoraphobia.
• Use of caffeine, alcohol, nicotine, or other substances can trigger or potentiate panic attacks.

Physical

No signs on physical or mental status examination are specific for panic disorder. The diagnosis is made primarily by history.

• If the patient presents in an acute state of panic, he or she can physically manifest any anticipated sign of an increased sympathetic state. These nonspecific signs may include hypertension, tachycardia, mild tachypnea, and mild tremors. The attack lasts 20-30 minutes from onset—rarely more than an hour. Somatic concerns of death from cardiac or respiratory problems may be a major focus of patients during an attack. Patients may end up in an emergency department.
• The Mental Status Examination may reveal an anxious-appearing person, although this is not required for diagnosis. Speech may reflect anxiety or urgency, or it may sound normal. Mood may be described as similar to "anxious," with congruent affect. Incongruent affect should raise consideration for other diagnostic possibilities. Thought processes should be logical, linear, and goal directed. Thought content is particularly important to specifically assess in order to ensure a patient has no suicidal or homicidal thoughts. Acute anxiety, as a form of acute mental anguish, can lead to unsafe behavior, usually directed against the self. Abnormalities in thought process or thought content (aside from impulsive suicidal thoughts) should prompt reconsideration of other etiologies. Insight and judgment are usually present and intact.

Causes

Panic disorder has moderate heritability, with heritability rates estimated to range from 0.3-0.6%. Segregation analyses have been inconclusive, and no distinct DNA linkages are known.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Acute stress/posttraumatic stress disorder
Adrenal dysfunction
Alcohol/sedative-hypnotic withdrawal
Drug intoxication
Generalized anxiety disorder
Pulmonary disease
Temporal lobe seizure activity
Vestibular dysfunction

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• No laboratory parameters are specific for panic disorder. Laboratory evaluation is performed to exclude any of the aforementioned differential diagnoses.

Imaging Studies

• No imaging study findings are currently specific for panic disorder, although they are performed to evaluate anatomic evidence of other diagnostic possibilities. Studies may include an EEG to exclude partial complex seizures.

Procedures

• No invasive procedures are required to diagnose panic disorder, although they may be useful in eliminating other differential diagnoses. History and physical/mental status examinations remain the diagnostic cornerstones.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

Pharmacotherapy, cognitive and behavioral psychotherapy, and other psychological treatment modalities are used to treat panic disorder.

Pharmacotherapy

Selective serotonin reuptake inhibitors (SSRIs) are generally used as first-line agents, followed by tricyclics. Benzodiazepines can achieve long-term control but should be reserved for patients with refractory panic disorder.

Fluoxetine (Prozac) can be used (especially if panic disorder occurs with depression); however, it may be poorly tolerated because it may initially increase anxiety, except at very low starting doses. Fluoxetine has a long half-life, making it a good choice in marginally compliant patients. Paroxetine (Paxil) has a more sedating effect, potentially making its potential aggravation of anxiety better tolerated initially. Both agents alter metabolism of cytochrome P-450 2D6–cleared agents; this fact should be considered. Paroxetine is also available in a controlled release preparation (Paxil CR), which may also improve tolerability.

Citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft) are likely to cause fewer hepatic enzyme interactions and may be appropriate initial choices for patients with complicated medical regimens or those who are concerned about drug interactions. Escitalopram also appears particularly well tolerated in preliminary studies.

Benzodiazepines act fast but carry the liability of dependence. Benzodiazepines can be reasonably used as an initial adjunct, while SSRIs are titrated to an effective dose. Benzodiazepines then can be tapered over 4-12 weeks while the SSRI is continued. This approach can potentially improve short-term tolerability.

Alprazolam (Xanax) has been widely used for panic disorder, but it is currently discouraged because of its higher dependence potential. Clonazepam (Klonopin) has become a favored replacement because it has a longer half-life and empirically elicits fewer withdrawal reactions upon discontinuation.

Cognitive and behavioral psychotherapy

Cognitive and behavioral psychotherapy can be used alone or in addition to pharmacotherapy. The combination approach yields superior results to either single modality.

Cognitive therapy helps patients understand false beliefs/distortions and provides information about panic attacks. Behavioral therapy involves sequentially greater exposure of the patient to anxiety-provoking stimuli; over time, the patient becomes desensitized to the experience. Relaxation techniques also help control patients' levels of anxiety. Respiratory training can help control hyperventilation during panic attacks. Other forms of psychological treatment are available but exceed the scope of this article.

• Prehospital care
• • Reassure and calm the patient.
  • Transport the patient to a medical treatment facility to exclude medical causes for the first attack or when suspected on subsequent attacks.
• Emergency department care
• • Acute panic disorder is best treated with benzodiazepines. The natural history of panic attacks is spontaneous remission of panic symptoms with anxiety about recurrence during the episode.
  • Prompt use of benzodiazepines can ease the uncomfortable anxiety associated with the attack and can provide the patient with definitive confidence that treatment can control the symptoms. This is particularly helpful for preventing subsequent visits to emergency services while longer-term therapy is helping the patient gain control.
  • Consultation with a psychiatrist is helpful to initiate longer-term therapy and to provide follow-up planning. Longer-term therapy currently consists of SSRIs, often with additional psychotherapeutic techniques.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Benzodiazepine therapy should be provided if acute symptoms are still present at the time of the interview or if significant apprehension about future attacks remains. If necessary, benzodiazepines are continued for a brief period (<2 wk).

Clonazepam has become the benzodiazepine of choice for outpatient use. Selecting patients for whom benzodiazepine therapy will be helpful rests on the clinician's sense of a patient's ability to control his or her symptoms until the next psychiatric appointment or until an SSRI might begin to control the symptoms (~2 wk). Alprazolam (Xanax) has been reviewed in the literature, although its use is currently discouraged because of its higher potential to elicit dependency.

Some patients may benefit from a standing dose of a benzodiazepine, whereas others do better with an as-needed (prn) dosing regimen. Longer-term control should be attempted with SSRIs if appropriate follow-up care is available. SSRIs are usually well tolerated, and appropriate follow-up care merely consists of meeting with the patient in 2 weeks to assess treatment efficacy and to deal with temporary symptom exacerbations right after beginning SSRIs.

Other antidepressants that have an effect on the serotonergic system have been used, especially when SSRIs have been ineffective or poorly tolerated. In the past, and sometimes even now, these have been the tricyclics and the monoamine oxidase inhibitors (MAOIs). More recently, venlafaxine (Effexor) and mirtazapine (Remeron) have been used. Beta-blockers, clonidine, calcium channel blockers, antipsychotics, buspirone, and anticonvulsants such as divalproex (Depakote) and gabapentin (Neurontin) have also been used as adjunctive agents in patients with refractory panic disorder, although these uses have not been approved by the US Food and Drug Administration.

Drug Category: Intermediate-acting benzodiazepines

By binding to specific receptor-sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters. These agents are effective on standing-dose and prn schedules.

Drug Category: Selective serotonin reuptake inhibitors

First-line agents for long-term management of anxiety disorders, with control gradually achieved over a 2- to 4-wk course, depending on required dosage increases.

All commonly used SSRIs appear to have a role in the treatment of panic disorder. Fluoxetine is covered herein because it has a very long half-life. This makes it well suited for patients who have difficulty remembering to take all of their medications each day. The longer half-life also minimizes the risk and severity of SSRI withdrawal that can occur when patients exhaust or abruptly discontinue their SSRI.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Inpatient care is rarely considered for uncomplicated panic disorder.

Further Outpatient Care

• Initial follow-up care should occur within 2 weeks because SSRIs can cause an initial exacerbation of panic symptoms. For this reason, begin with the lowest dose with the understanding that the dose must be increased at the initial follow-up visit.
• Providing a few doses of a benzodiazepine for prn use can enhance patient confidence and compliance.

Prognosis

• Prognosis is excellent with adherence to medical management.

Patient Education

• Educate patients on potential adverse effects of their treatment medications.
• Obtain informed consent for psychotropic medications.
• Document the discussion of the risks and benefits of treatment medications.
• Inform patients that causes are likely biological and psychosocial.
• Advise patients to avoid anxiogenic substances such as caffeine.
• Consider educating patients diagnosed with panic disorder on cognitive distortions that may help amplify anxiety. Also educate patients about recognizing trigger stimuli so they can contribute this to their psychological treatment approach.
• Discuss alcohol consumption and any recreational drug use because these psychoactive substances can impact the course of panic disorder. While some substances may seem to avert the anguish of an acute attack, they often compromise the long-term treatment plan.
• For excellent patient education resources, visit eMedicine's Anxiety Center. Also, see eMedicine's patient education articles Anxiety, Panic Attacks, and Hyperventilation.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Failure to recognize an underlying medical etiology
• Failure to document informed consent for medications
• Failure to document warnings to patients about the potential adverse effects (eg, sedation) of treatment medications

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Sandra Yerkes to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Press;2000.
• American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. Am J Psychiatry. May 1998;155(5 Suppl):1-34. [Medline].
• Bandelow B, Behnke K, Lenoir S, et al. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. J Clin Psychiatry. Mar 2004;65(3):405-13. [Medline].
• Fogel BS, Schiffer RB, Rao SM, eds. Neuropsychiatry. 1st ed. Baltimore, Md: Williams & Wilkins; 1996:. 263-8.
• Hales RE, Yudofsky SC, Talbott JA, eds. APA Textbook of Psychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1999.
• Kaplan HI, Sadock BJ, eds. Synopsis of Psychiatry. Behavioral Sciences/Clinical Psychiatry. 8th ed. Baltimore, Md: Williams & Wilkins; 1997:. 594-603.
• Pollack MH, Simon NM, Worthington JJ, et al. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. Sep 2003;17(3):276-82. [Medline].
• Sadock BJ, Sadock VA, Kaplan HI. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. Baltimore, Md: Williams & Wilkins; 2000:. 1445-90.
• Stahl SM, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. Nov 2003;64(11):1322-7. [Medline].
• Swoboda H, Amering M, Windhaber J, Katschnig H. The long-term course of panic disorder--an 11 year follow-up. J Anxiety Disord. 2003;17(2):223-32. [Medline].

Article Last Updated: Apr 13, 2006