AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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

INTRODUCTION

Section 2 of 11  

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

Background

Anxiety disorders are common psychiatric disorders. Many patients with anxiety disorders experience physical symptoms related to anxiety and subsequently visit their primary care providers. Despite the high prevalence rates of these anxiety disorders, they often are underrecognized and undertreated clinical problems. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) classifies the anxiety disorders into the following categories:⁴

• Anxiety due to a general medical condition
• Substance-induced anxiety disorder
• Generalized anxiety
• Panic disorder
• Acute stress disorder
• Posttraumatic stress disorder (PTSD)
• Adjustment disorder with anxious features
• Social phobia
• Obsessive-compulsive disorder (OCD)
• Specific phobias

See Medscape's Anxiety Disorders Resource Center.

Pathophysiology

Anxiety disorders appear to be caused by an interaction of biopsychosocial factors, including genetic vulnerability, which interact with situations, stress, or trauma to produce clinically significant syndromes. In the central nervous system, the major mediators of the symptoms of anxiety disorders appear to be norepinephrine and serotonin. Other neurotransmitters and peptides, such as corticotropin-releasing factor, may be involved. Peripherally, the autonomic nervous system, especially the sympathetic nervous system, mediates many of the symptoms.

Frequency

United States

Two major studies in the United States have estimated the prevalence rates for a variety of anxiety disorders. These 2 studies are the Epidemiological Catchment Area (ECA) study¹ and the National Comorbidity Survey (NCS) study². Using these and other studies, the estimated lifetime prevalence rates for individual anxiety disorders are panic disorder (2.3-2.7%), generalized anxiety disorder (4.1-6.6%), OCD (2.3-2.6%), PTSD (1-9.3%), and social phobia (2.6-13.3%).

International

The prevalence of specific anxiety disorders appears to vary between countries and cultures. A cross-national study of the prevalence of panic disorder found lifetime prevalence rates ranging from 0.4% in Taiwan to 2.9% in Italy. A cross-cultural study of the prevalence of OCD found lifetime prevalence rates ranging from 0.7% in Taiwan to 2.5% in Puerto Rico.³

Mortality/Morbidity

• Anxiety disorders may contribute to morbidity and mortality through neuroendocrine and neuroimmune mechanisms or by direct neural stimulation, eg, hypertension or cardiac arrhythmia.
• Severe anxiety disorders may be complicated by suicide, with or without secondary mood disorders (eg, depression). Anxiety disorders have high rates of comorbidity with major depression and alcohol and drug abuse. Some of the increased morbidity and mortality associated with anxiety disorders may be related to this high rate of comorbidity. The ECA study found that panic disorder was associated with suicide attempts (odds ratio=18 compared to populations without psychiatric disorders). How much of the association of panic disorder with suicide is mediated through the association of panic disorder with mood and substance abuse disorders is unclear. Acute stress may play a role in producing suicidal behavior. Suicide attempts can be precipitated by adverse life events such as divorce or financial disaster. The effects of acute stress in producing suicidal behavior are increased in those with underlying mood, anxiety, and substance abuse problems.
• Chronic anxiety may be associated with increased risk for cardiovascular morbidity and mortality.

Race

• The ECA study found no difference in rates of panic disorder among white, African American, or Hispanic populations in the United States.
• Some studies have found higher rates of PTSD in minority populations. Some of this association may be due to higher rates of specific traumatic events (ie, assault) in minority populations.

Sex

• The female-to-male ratio for any lifetime anxiety disorder is 3:2.

Age

• Most anxiety disorders begin in childhood, adolescence, and early adulthood. Separation anxiety is an anxiety disorder of childhood that often includes anxiety related to going to school. This disorder may be a precursor for adult anxiety disorders. Panic disorder demonstrates a bimodal age of onset in the NCS study in the age groups of 15-24 years and 45-54 years. The median age of onset of social phobia in the NCS study was 16 years. The age of onset for OCD appears to be in the mid 20s to early 30s.
• New-onset anxiety symptoms in older adults should prompt a search for an unrecognized general medical condition, a substance abuse disorder, or major depression with secondary anxiety symptoms.

CLINICAL

Section 3 of 11  

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

History

Symptoms vary depending on the specific anxiety disorder. To rule out anxiety disorders secondary to general medical or substance abuse conditions, a detailed history and review of symptoms is essential. Review use of caffeine-containing beverages (coffee, tea, colas, Mountain Dew), over-the-counter medications (aspirin with caffeine, sympathomimetics), herbal "medications," or street drugs. Ask the patient's sleep partner about apneic episodes or myoclonic limb jerks. Concurrent depressive symptoms are common in all of the anxiety disorders. Severe anxiety disorders may produce agitation, suicidal ideation, and increased risk of completed suicide. Always ask about suicidal ideation or suicidal intent.  

• Panic disorder is characterized by recurrent panic attacks (ie, periods of intense fear of abrupt onset peaking in intensity within 10 min). Four of the following must be present for a panic attack:
• • Palpitations, pounding heart, or accelerated heart rate
  • Sweating
  • Trembling or shaking
  • Shortness of breath or dyspnea
  • Sensation of choking
  • Chest pain or discomfort
  • Nausea or abdominal distress
  • Feeling dizzy, unsteady, lightheaded, or faint
  • Derealization or depersonalization
  • Fear of losing control or going crazy
  • Fear of dying
  • Paresthesias
  • Chills or hot flashes
  • Although not a diagnostic feature, suicidal ideation and completed suicide have been associated with panic disorder.
• Generalized anxiety disorder is characterized by excessive anxiety and worry. Worrying is difficult to control. Anxiety and worry are associated with at least 3 of the following symptoms:
• • Restlessness or feeling keyed-up or on edge
  • Being easily fatigued
  • Difficulty concentrating or mind going blank
  • Irritability
  • Muscle tension
  • Sleep disturbance
  • Although not a diagnostic feature, suicidal ideation and completed suicide have been associated with generalized anxiety disorder.
• OCD is characterized by obsessions or compulsions. Obsessions or compulsions must be recognized as unreasonable or excessive and must cause marked distress.
• • Obsessions include all of the following:
  • • Recurrent and persistent thoughts, impulses, or images that are intrusive and knowingly inappropriate and cause anxiety or distress
    • Thoughts, impulses, or images that are not simply excessive worries about real-life problems
    • Attempts are made to ignore or suppress thoughts.
    • Thoughts, impulses, or images are recognized as being the product of the mind and not imposed from an outside force.
  • Compulsions include the following:
  • • Repetitive behaviors, such as handwashing, ordering, and checking, that people feel are driven and must be carried out and occur to such an extreme that a person's ability to function is impaired.
    • Behaviors or mental acts are done to reduce distress or anxiety.
• Social phobia
• • Marked and persistent fear of social or performance situations to the extent that a person's ability to function at work or in school is impaired.
  • Exposure to social or performance situation always produces anxiety.
  • Fear/anxiety recognized as excessive
  • Social or performance situations are avoided or endured with intense anxiety.
  • Avoidance behavior, anticipation, or distress in the feared social or performance setting produces significant impairment in functioning.
• PTSD is a severe trauma that is experienced that includes (1) actual or threatened death or serious injury or threat to personal integrity of self or others and (2) responses that include intense fear, helplessness, or horror. (Life-threatening experiences and the attendant loss of control are key elements.)
• • Persistent reexperience of the event occurs by at least 1 of the following:
  • • Recurrent and intrusive recollections
    • Recurrent distressing dreams/nightmares
    • Feelings of reliving traumatic event, ie, flashbacks
    • Intense psychologic distress with internal or external cues to the trauma
    • Physiological reactivity on exposure to trauma cues
  • Persistent avoidance of stimuli of trauma and numbing/avoidance behavior demonstrated by at least 3 of the following:
  • • Avoidance of thoughts or conversation related to the trauma
    • Avoidance of activities, places, or people related to the trauma
    • Amnesia for important trauma-related events
    • Decreased participation in significant activities
    • Feeling detached or estranged from others
    • Restricted affect
    • Foreshortened sense of the future
  • Persistent symptoms of increased arousal demonstrated by 2 or more of the following:
  • • Difficulty staying or falling asleep
    • Irritability or anger outbursts
    • Difficulty concentrating
    • Hypervigilance
    • Exaggerated startle response
  
  
  • Although not a diagnostic feature, suicidal and homicidal ideation have been associated with PTSD.

Physical

• Tremor
• Tachycardia
• Tachypnea
• Sweaty palms
• Restlessness

Causes

• First, evaluate for anxiety due to a known or unrecognized medical condition.
• Most presenting anxiety disorders are functional psychiatric disorders.
• Substance-induced anxiety disorder (over-the-counter medications, herbal medications, substances of abuse) is a diagnosis that often is missed.

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

Adult respiratory distress syndrome (ARDS)
AIDS
Thyrotoxicosis

Anxiety disorders have one of the longest differential diagnosis lists of all psychiatric disorders. Anxiety is a nonspecific syndrome and can be due to a variety of medical or psychiatric syndromes. A variety of anxiety symptoms, such as panic, worry, rumination, and obsessions, can present in a variety of psychiatric illnesses including mood disorders, psychotic disorders, personality disorders, somatoform disorders, and cognitive impairment disorders (eg, delirium). Anxiety also can be observed as part of a drug withdrawal or drug intoxication effect.

Other important causes in the differential include medication-induced anxiety (ie, due to epinephrine or other sympathomimetics, theophylline or other neurostimulant bronchodilators, analgesics containing caffeine, corticosteroids, antivirals, others); migraine, seizure disorders, or other CNS-based disorders; and sleep disorders such as restless legs syndrome, sleep apnea, and periodic limb movement. Heroin abuse also should be considered in the differentials.

WORKUP

Section 5 of 11  

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

Lab Studies

• When the index of suspicion for anxiety being produced by a medical disorder is low (lack of physical findings, younger age, typical anxiety disorder presentation), initial lab studies might be limited to the following:
• • CBC count
  • Chemistry profile
  • Thyroid function tests
  • Urinalysis
  • Urine drug screen
• For presentations with a higher index of suspicion for other medical causes of anxiety (ie, atypical anxiety disorder presentation, older age, specific physical examination abnormalities), more detailed evaluations may be indicated as follows:
• • Rule out CNS disorder using electroencephalogram, lumbar puncture, or brain CT scan, as indicated by history and associated clinical findings.
  • Rule out cardiac disorder using ECG or treadmill ECG.
  • Rule out infectious causes using rapid plasma reagent test, lumbar puncture (CNS infections), or HIV testing.

Imaging Studies

• Diagnostic imaging studies are not indicated in the diagnosis of primary anxiety disorders unless specific general medical conditions need to be ruled out.
• Imaging studies may be helpful, however, to rule out anxiety due to a general medical condition, eg, cephalic CT scan or MRI to evaluate for pathological intracranial processes.

Procedures

• Psychosurgery is used in rare cases of severe treatment-refractory OCD.
• Electroconvulsive therapy is not effective for anxiety disorders but may successfully treat comorbid conditions, such as severe major depression, and is especially indicated when the patient is at high risk for suicide.

TREATMENT

Section 6 of 11  

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

Medical Care

Patients with panic disorder frequently present to the emergency department with chest pain or dyspnea, fearing that they are dying of myocardial infarction. Anxiety symptoms often accompany or can exacerbate respiratory conditions such as asthma and chronic obstructive pulmonary disease.

• If clinically indicated, obtain necessary studies to rule out myocardial infarction and pulmonary embolism (ECG, chest x-ray).
• Intravenous or oral acute sedation with benzodiazepines may be used. Untreated panic attacks can subside spontaneously within 20-30 minutes, especially with reassurance and a calming environment.
• If possible, avoid long-term benzodiazepines for chronic anxiety disorders. If this approach seems necessary, obtaining a confirming opinion from a consulting psychiatrist may be helpful.

Consultations

• Most often, psychiatrists are consulted.
• In anxiety disorders secondary to a general medical condition, specialty consultation may be indicated.

Diet

• Discontinue (or decrease to a low reasonable level) caffeine-containing products such as coffee, tea, colas, and Mountain Dew.
• Over-the-counter preparations and herbal remedies should be reviewed with special caution because ephedrine and other herbal compounds may precipitate or exacerbate anxiety symptoms.

Activity

• If no medical contraindication exists, recommend at least a mild-to-moderate daily exercise program.

MEDICATION

Section 7 of 11  

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

The management of individual anxiety disorders is dependent on the specific diagnosis.

Selective serotonin reuptake inhibitors (SSRIs) are helpful in a variety of anxiety disorders, including generalized anxiety disorder, panic disorder, OCD, and social phobia.

Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer agents that have a safer adverse effect profile and higher ease of use than the older tricyclic agents; however, benzodiazepines often are used as adjunct treatment.

Some anticonvulsant medications, such as divalproex and gabapentin, may have a role in the treatment of anxiety disorders, especially in patients with high potential for abusing benzodiazepines.

Older antidepressants, such as tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) also are effective in the treatment of some anxiety disorders. Caution in their use is warranted due to their higher toxicity and potential lethality in overdose. Their use should be limited to cases where SSRIs are ineffective or cannot be afforded. MAOIs may be especially indicated in treatment-refractory panic disorder. Clomipramine (Anafranil, a tricyclic agent) has a US Food and Drug Administration (FDA) indication in the treatment of OCD and is the only tricyclic agent effective in the treatment of this condition. Indeed, it can be effective in cases refractory to treatment with SSRI agents. MAOI agents also may have a role in the treatment of certain subtypes of OCD refractory to conventional treatment, such as patients with symmetry obsessions or associated panic attacks.

The FDA has granted specific indications to the following disorders and agents: generalized anxiety disorder (venlafaxine, buspirone, escitalopram, paroxetine, duloxetine), social phobia (paroxetine, sertraline, venlafaxine), OCD (fluoxetine, sertraline, paroxetine, fluvoxamine), and PTSD (sertraline, paroxetine).

All SSRIs may be equal in the treatment of anxiety disorders; however, higher doses may be necessary in the treatment of OCD. Antidepressants that are not FDA-approved for the treatment of a given anxiety disorder, such as nefazodone and mirtazapine, still may be beneficial. Patients with panic disorder may be more sensitive to treatment with antidepressants and frequently need lower initial doses and slower titration to accomplish successful therapy.

Benzodiazepines are especially useful in the management of acute situational anxiety disorder and adjustment disorder where the duration of pharmacotherapy is anticipated to be 6 weeks or less and for the rapid control of panic attacks. If long-term use of benzodiazepines seems necessary, obtaining a confirmatory opinion from a second clinician may be helpful because chronic benzodiazepine use may be associated with tolerance, withdrawal, and treatment-emergent anxiety.

The risk of addiction potential with benzodiazepines should be carefully considered before use in the anxiety disorders. Avoid use in patients with a prior history of alcohol or other drug abuse.  Closely monitor for evidence of unauthorized dose escalation or obtaining benzodiazepine prescriptions from multiple sources.

Drug Category: Benzodiazepines

Several drugs in the benzodiazepine class can be used for the short-term (£6 wk) control of anxiety. Drugs in this class include lorazepam, diazepam, clonazepam, and chlordiazepoxide.

Drug Category: Serotonin and norepinephrine reuptake inhibitors

Pharmacologic agents with both reuptake inhibition of serotonin and norepinephrine may be helpful in a variety of mood and anxiety disorders.

Drug Category: Antianxiety agents

Buspirone is a novel antianxiety agent with no other members in its class.

Drug Category: Tricyclic antidepressants

A complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects.

Drug Category: Antidepressant, Serotonin Reuptake Inhibitor

These agents specifically inhibit presynaptic reuptake or serotonin but not noradrenaline.

FOLLOW-UP

Section 8 of 11  

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

Further Inpatient Care

• Inpatient care rarely is needed for the management of anxiety disorders unless complicated by comorbid conditions such as affective or substance abuse disorders or general medical conditions.
• Inpatient care should be considered if suicide is a risk or detoxification is needed for comorbid substance dependence.

Further Outpatient Care

• Anxiety disorders often are chronic and require ongoing medical/psychiatric care, including psychosocial therapies and medication (pharmacotherapy).
• Psychosocial interventions in anxiety disorder
• • Cognitive-behavioral therapy often is efficacious and is the treatment of choice for specific phobias. It often is used alone or in combination with pharmacotherapy in the treatment of OCD and panic disorder.
  • Other psychotherapeutic approaches, such as interpersonal therapy or psychodynamic therapy, also may be helpful in the treatment of anxiety disorders.
  • Marital therapy, family therapy, or group therapy may be helpful adjunct therapies in the long-term management of severe anxiety disorders. Educating families and friends enables them to cope with their loved one's disease.

In/Out Patient Meds

• See Medication for recommendations for specific anxiety disorders.
• • Generalized anxiety disorder
  • Panic disorder
  • OCD
  • Simple phobia
  • Social phobia
  • PTSD
  • Adjustment disorder with anxious mood

Complications

• Agoraphobia
• Major depression
• Suicide
• Homicide (especially in patients with PTSD)
• Alcohol abuse and dependence
• Sedative abuse and dependence
• Social dysfunction and withdrawal
• Occupational impairment
• Marital and familiar dysfunction, divorce

Prognosis

• Anxiety disorders can range from mild and transient to severe and chronic.
• Early treatment improves prognosis and limits social and occupational impairment.

Patient Education

• Education can be obtained through books, newsletters, support groups, and the Internet. Some useful Web sites are as follows:
• • National Institute of Mental Health, Anxiety Disorders
  • SAMHSA's National Mental Health Information Center, Anxiety Disorders
  • MentalHelp.net
  • eMedicineHealth, Mental Health and Behavior Center and Anxiety Center
  • eMedicineHealth, Stress, Anxiety, Panic Attacks, and Hyperventilation
• Family members should receive information about the effect of anxiety disorders on mood, behavior, and relationships. Family members can assist in care by reinforcing the need for medical treatment and supervision. Family members may also assist by providing a collaborative resource for monitoring the severity of the patient's anxiety symptoms and response to treatment interventions. 

MISCELLANEOUS

Section 9 of 11  

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

Medical/Legal Pitfalls

• Failure to identify a medical or psychiatric cause for anxiety
• Unnecessary and invasive diagnostic testing for physical symptoms caused by anxiety
• Benzodiazepine prescription use in those with comorbid alcohol or drug dependence
• Failure to recognize cognitive and motor impairment related to chronic high-dose benzodiazepine use
• Failure to recognize factitious disorder with psychological symptoms or malingering to obtain benzodiazepine prescription

MULTIMEDIA

Section 10 of 11  

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

Media file 1:  Chart showing the female-to-male sex ratio for anxiety disorders. Adapted from Kessler et al, 1994.
	View Full Size Image
Media type:  Graph

REFERENCES

Section 11 of 11

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

1. Robins, LN, Regier, DA. Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. The Free Press; 1990.
2. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. Jan 1994;51(1):8-19. [Medline].
3. Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK. The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry. Mar 1994;55 Suppl:5-10. [Medline].
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Washington, DC: American Psychiatric Association; 2000.
5. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. American Psychiatric Association. Am J Psychiatry. May 1998;155(5 Suppl):1-34. [Medline].
6. Bernstein GA, Shaw K. Practice parameters for the assessment and treatment of children and adolescents with anxiety disorders. American Academy of Child and Adolescent Psychiatry. J Am Acad Child Adolesc Psychiatry. Oct 1997;36(10 Suppl):69S-84S. [Medline].
7. Bisson J, Andrew M. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2005;CD003388. [Medline].
8. Breslau N, Peterson EL, Poisson LM, Schultz LR, Lucia VC. Estimating post-traumatic stress disorder in the community: lifetime perspective and the impact of typical traumatic events. Psychol Med. Jul 2004;34(5):889-98. [Medline].
9. Connolly SD, Bernstein GA,. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. Feb 2007;46(2):267-83. [Medline].
10. Jenike MA. Clinical practice. Obsessive-compulsive disorder. N Engl J Med. Jan 15 2004;350(3):259-65. [Medline].
11. Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. Mar 6 2007;146(5):317-25. [Medline].
12. Roy-Byrne PP, Craske MG, Stein MB, et al. A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Arch Gen Psychiatry. Mar 2005;62(3):290-8. [Medline].
13. Stein MB, Simmons AN, Feinstein JS, Paulus MP. Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am J Psychiatry. Feb 2007;164(2):318-27. [Medline].
14. Torres AR, Prince MJ, Bebbington PE, Bhugra D, Brugha TS, Farrell M. Obsessive-compulsive disorder: prevalence, comorbidity, impact, and help-seeking in the British National Psychiatric Morbidity Survey of 2000. Am J Psychiatry. Nov 2006;163(11):1978-85. [Medline].
15. Weissman MM, Bland RC, Canino GJ, et al. The cross-national epidemiology of panic disorder. Arch Gen Psychiatry. Apr 1997;54(4):305-9. [Medline].
16. Yehuda R, Flory JD, Southwick S, Charney DS. Developing an agenda for translational studies of resilience and vulnerability following trauma exposure. Ann N Y Acad Sci. Jul 2006;1071:379-96. [Medline].

Article Last Updated: Aug 13, 2008