eMedicine Specialties > Emergency Medicine > Psychosocial

Panic Disorders

Michael C Plewa, MD, Research Coordinator, Consulting Staff, Department of Emergency Medicine, Lucas County Emergency Physicians, Inc, and Saint Vincent Mercy Medical Center

Updated: May 7, 2009

Introduction

Background

An understanding of panic disorder (PD) is important for emergency physicians because patients with panic disorder frequently present to the emergency department (ED) with various somatic complaints. As many as 70% of persons with panic disorder are unrecognized as having this condition, and few individuals with panic disorder are referred to mental health professionals.

Persons with panic disorder have a 4-fold higher risk of alcohol abuse and an 18-fold higher risk of suicide than the general population (although some studies suggest that panic disorder itself is not a risk factor for suicide in the absence of other risks, such as affective disorders, substance abuse, eating disorders, and personality disorders).¹ Serious medical problems, such as asthma or cardiac dysrhythmia, or metabolic disturbances, such as hypoglycemia, hypoxia, and thyroid storm, can mimic panic attack.

Following exclusion of somatic disease and other psychiatric disorders, confirmation of the diagnosis with a brief mental status screening examination and initiation of appropriate treatment and referral is time- and cost-effective in these patients who have high rates of medical resource use.

See Medscape's Anxiety Disorders Resource Center for more information.

Pathophysiology

Panic disorder appears to be a genetically inherited neurochemical dysfunction that may involve autonomic imbalance; allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol;² diminished benzodiazepine receptor function; and disturbances in serotonin,³ norepinephrine, gamma-aminobutyric acid, dopamine, cholecystokinin, and interleukin-1-beta.⁴ Some theorize that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor hypersensitivity.⁵ Some epileptic patients have panic as a manifestation of their seizures.

Positron emission tomography (PET) scanning has demonstrated increased flow in the right parahippocampal region and reduced serotonin type 1A receptor binding in the anterior and posterior cingulate and raphe of patients with panic disorder.³ Magnetic resonance imaging (MRI) has demonstrated smaller temporal lobe volume despite normal hippocampal volume in these patients.⁶

In experimental settings, symptoms can be elicited in people with panic disorder by hyperventilation, inhalation of carbon dioxide, caffeine consumption, or intravenous infusions of sodium lactate, cholecystokinin, isoproterenol, or flumazenil.⁵

The cognitive theory regarding panic is that these patients have a heightened sensitivity to internal autonomic cues (eg, tachycardia).

Panic disorder is associated with depression, obsessive-compulsive disorder, restless leg syndrome,⁷ fatigue,⁸ specific phobias, social phobia, agoraphobia (ie, fear of being unsafe in public settings), irritable bowel syndrome, migraine, mitral valve prolapse, and alcohol and drug abuse. Individuals with panic disorder also have lower oxygen consumption and exercise tolerance than the general population.⁹ They also have reduced heart rate variability and increased QT variability on electrocardiography and may have a higher risk of cardiovascular disease and sudden death.¹⁰

Frequency

United States

Panic disorder has an approximate 1-5% prevalence in the population.

International

Prevalence is similar to that in the United States.

Mortality/Morbidity

• Panic disorder can lead to a significant hindrance in lifestyle (many people with agoraphobia are unable to travel alone or be in crowds, malls, or on public transportation), including problems with employment, depression, substance abuse, and suicide.
• Panic disorder is present in 30% of patients with chest pain and normal findings on angiography, 5-40% of persons with asthma, 15% of patients with headache, 20% of patients with epilepsy, 8-15% of individuals in alcohol treatment programs, and 10% of patients in primary care settings.
• Panic disorder may be associated with a higher risk of cardiovascular disease and sudden death.
• A variant of panic disorder unrelated to fear (nonfearful panic disorder [NFPD]) is associated with high rates medical resource use (32-41% of patients with panic disorder seeking treatment for chest pain) and poor prognosis.¹¹

Sex

• Prevalence is higher in females than in males, with a female-to-male ratio of approximately 2:1.
• Panic is more common in women who have never been pregnant and during the postpartum period, but it is less common during pregnancy.

Age

• Although panic can occur in people at any age, the average age of onset, as with most anxiety disorders, is in the third decade of life, and it usually occurs between the ages of 18 and 45 years.
• Panic disorder has a bimodal age of onset, with patients with late-onset panic disorder having less mental health use, lower comorbidity and hypochondriasis, and better coping behavior.¹²

Clinical

History

• Patients who experience panic attack report a spontaneous sudden onset of fear or discomfort, typically reaching a peak within 10 minutes.
• Attacks are associated with a constellation of systemic symptoms, including the following (4 or more of these are needed for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria):
  • Palpitations, pounding heart, or accelerated heart rate
  • Sweating
  • Trembling or shaking
  • Shortness of breath or feeling of smothering
  • Choking sensation
  • Chest pain or discomfort
  • Nausea or abdominal distress
  • Feeling dizzy, unsteady, lightheaded, or faint
  • Derealization (ie, feeling of unreality) or depersonalization (ie, being detached from oneself)
  • Fear of losing control or going crazy
  • Fear of dying
  • Paresthesias (ie, numbness or tingling sensations)
  • Chills or hot flashes
• During the episode, patients have the urge to flee or escape and have a sense of impending doom (as though they are dying from a heart attack or suffocation).
• Other symptoms may include headache, cold hands, diarrhea, insomnia, fatigue, intrusive thoughts, and ruminations.
• Patients with panic disorder have recurring episodes of panic, with the fear of recurrent attack resulting in significant behavioral changes (eg, avoiding situations or locations) and worry about the implications of the attack or its consequences (eg, losing control, going crazy, dying).
• Panic disorder may result in changes in personality traits, characterized by the patient becoming more passive, dependent, or withdrawn.
• DSM-IV criteria include 4 or more attacks in a 4-week period or 1 or more attacks followed by at least 1 month of fear of another.
• Agoraphobia, present in 30% of persons with PD, establishes the diagnosis.
• Assess precipitating events, suicidal ideation or plan, phobias, agoraphobia, and obsessive-compulsive behavior.
• Exclude involvement of alcohol, illicit drugs (eg, cocaine, amphetamine, phencyclidine, amyl nitrate, lysergic acid diethylamide [LSD], yohimbine, 3,4-methylenedioxymethamphetamine [MDMA, ecstasy]), cannabis, and medications (eg, caffeine, theophylline, sympathomimetics, anticholinergics).
• Consider symptomatology of other medical disorders, which may manifest with anxiety as a primary symptom.
  • Angina and myocardial infarction (eg, dyspnea, chest pain, palpitations, diaphoresis)
  • Cardiac dysrhythmias (eg, palpitations, dyspnea, syncope)
  • Mitral valve prolapse
  • Pulmonary embolus (eg, dyspnea, hyperpnea, chest pain)
  • Asthma (eg, dyspnea, wheezing)
  • Hyperthyroidism (eg, palpitations, diaphoresis, tachycardia, heat intolerance)
  • Hypoglycemia
  • Pheochromocytoma (eg, headache, diaphoresis, hypertension)
  • Hypoparathyroidism (eg, muscle cramps, paresthesias)
  • Transient ischemic attacks (TIAs)
  • Seizure disorders
• Consider other mental illnesses that may result in panic attacks, including schizophrenia, manic disorder, depressive disorder, posttraumatic stress disorder, phobic disorders, and somatization disorder.
• Assess family history of panic or other psychiatric illness.

Physical

• The patient may have an anxious appearance.
• Tachycardia and tachypnea are common; blood pressure and temperature may be within the reference range.
• Cool clammy skin may be observed.
• Hyperventilation may be difficult to detect by observing breathing because respiratory rate and tidal volume may appear normal.
  • Patients may have frequent sighs or difficulty with breath holding.
  • Reproduction of symptoms with overbreathing is unreliable.
  • Chvostek sign, Trousseau sign, or overt carpopedal spasm may be present.
• Mental status screening is essential for diagnosis. Standardized examinations include the following:
  • Primary Care Evaluation of Mental Disorders (PRIME-MD)
  • Mobility Inventory for Agoraphobia (MIA)
  • The Agoraphobia Cognitions Questionnaire (ACA)
  • The Body Sensations Questionnaire (BSQ)
• The remaining examination findings are typically normal in panic disorder. However, remember that panic disorder is largely a diagnosis of exclusion, and attention should be focused on the exclusion of other disorders.

Causes

Triggers of panic can include the following:

• Injury (eg, accidents, surgery)
• Illness
• Interpersonal conflict or loss
• Use of cannabis (can be associated with panic attacks, perhaps because of breath-holding)¹³
• Use of stimulants, such as caffeine, decongestants, cocaine, and sympathomimetics (eg, amphetamine, MDMA)¹⁴
• Certain settings, such as stores and public transportation (especially in patients with agoraphobia)

Differential Diagnoses

Other Problems to Be Considered

Pheochromocytoma
Huntington chorea

Workup

Laboratory Studies

• Arterial blood gas analysis is useful in confirming hyperventilation (respiratory alkalosis) and excluding hypoxemia or metabolic acidosis. The presence of hypoxemia with hypocapnia or a widened alveolar-arterial (A-a) gradient should increase the suspicion of pulmonary embolus.
• Electrolyte analysis is unnecessary, although several abnormalities may be present in the setting of hyperventilation.
  • Serum phosphorus and ionized calcium may be diminished in patients with hyperventilation and carpopedal spasm, Chvostek sign, or Trousseau sign.
  • The serum calcium level may be within the reference range.
• Other laboratory studies may be necessary to exclude other medical disorders, as follows:
  • Serum electrolytes to exclude hypokalemia and acidosis
  • Serum glucose to exclude hypoglycemia
  • Cardiac enzymes in patients suspected of acute coronary syndromes
  • Serum hemoglobin in patients with near-syncope
  • Thyroid-stimulating hormone (TSH) in patients suspected of hyperthyroidism
  • Urine toxicology screen for amphetamines, cocaine, and phencyclidine in patients suspected of intoxication
  • D-dimer assay to exclude pulmonary embolism
    

Imaging Studies

• Chest radiography is useful in excluding other causes of dyspnea with chest pain.

Other Tests

• Room air pulse oximetry values are within the reference range or at the upper limit of the reference range.
• End-tidal capnography values are typically less than 30 torr during hyperventilation.
• Electrocardiography (ECG) should be inspected for signs of ventricular preexcitation (short PR and delta wave), short or long QT interval in patients with palpitations, and for ischemia, infarction, or pericarditis patterns in patients with chest pain.
• Outpatient Holter monitoring or transtelephonic event recording is rarely necessary but should be considered in patients with palpitations associated with syncope or near-syncope.
• Patients who may be at risk for pulmonary embolus require appropriate testing (eg, determination of d-dimer level, spiral CT scan, ventilation-perfusion [V/Q] scan, duplex Doppler/ultrasonography, or pulmonary angiography).

Treatment

Prehospital Care

• Supplemental oxygen and cardiac monitoring are recommended for patients experiencing dyspnea or chest pain.
  

Emergency Department Care

• Patients with chest pain, dyspnea, palpitations, or near-syncope should be placed on oxygen and in a supine or Fowler position; monitor them with pulse oximetry, ECG, and frequent vital signs (including one set of orthostatic vital signs, when possible).
• Patients with panic disorder may require frequent reassurance and explanation. Many may benefit from social service intervention.
• A major component of therapy involves education that the symptoms are neither from a serious medical condition nor from a mental deficiency but rather from a chemical imbalance in the fight or flight response. This alone may allow a 30-50% placebo response rate.
• The ED staff must listen effectively and remain empathic and nonargumentative. Statements made by healthcare staff such as, "It's nothing serious," and "It's related to stress," are frequently misinterpreted as implying lack of understanding and concern.
• Intravenous medication (eg, Ativan 0.5 mg IV q20min) may be necessary in patients with panic disorder who, as a result of subsequent poor impulse control, pose a risk to themselves or to those around them.
• Patients with panic disorder are probably best served by referral to a psychiatrist, before beginning anxiolytic medications, because the psychiatrist can establish a constructive rapport with them and follow their needs on a long-term basis.
  • Institution of treatment for panic disorder in the ED is appropriate in a very limited subset of patients with panic disorder who are very motivated, cooperative, possess an understanding of the psychological nature of their disorder, and whose symptomatology is elicited as a response to a temporary stress.
  • In such cases, pharmacotherapy with an oral benzodiazepine for a brief duration (approximately 1 wk) may be appropriate.

Consultations

• Consult a cardiologist for patients with abnormal ECG findings, ventricular dysrhythmia, abnormal cardiac examination, or risk factors for ischemic heart disease.
• Consult a chemical dependence treatment specialist in cases of significant intoxication or withdrawal.
• Refer all patients with panic disorder for psychiatric or mental health follow-up care and to support groups.

Medication

Aside from IV medications required to treat acute anxiety states in the ED, the use of pharmacotherapy for patients with panic disorder (PD) should, in most instances, be deferred to the primary physician or psychiatrist who is monitoring the patient long term. Benzodiazepines are optimal for ED and outpatient abortive therapy because of their immediate antipanic effects. Selective serotonin reuptake inhibitors (SSRIs) are becoming first-line preventive agents in panic disorder because of a better safety profile.^15,16  Some patients will require concomitant benzodiazepine with SSRI therapy for the first several weeks of SSRI therapy.

Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are used in refractory cases. Coexisting disorders may influence medication choice (eg, MAOIs, clonazepam, or SSRIs for social phobia; SSRIs or clomipramine [Anafranil] for obsessive-compulsive disorder; TCAs for depression). Beta-blockers, clonidine, and buspirone, although promising in theory, have had poor efficacy in panic disorder. Newer agents such as bupropion (Wellbutrin), nefazodone (Serzone), mirtazapine (Remeron), and the serotonin norepinephrine reuptake inhibitors (SNRIs), venlafaxine (Effexor) and duloxetine (Cymbalta), have not been FDA approved for use in panic disorder. Older agents, such as valproate (Depakote) and hydroxyzine (Vistaril), may also be effective, but they have not been FDA approved for use in panic disorder.

Aripiprazole (Abilify), olanzapine (Zyprexa), or tiagabine (Gabitril) may be effective in augmentation therapy, in combination with an SSRI, in resistant panic disorder cases.

Benzodiazepines

These should not be prescribed to patients who have a history of alcohol and/or drug abuse or emotional dependence. Most common side effects are sedation, somnolence, memory impairment, and poor coordination.

Alprazolam has been studied best and is an effective agent with a rapid (20-min) onset and short (12- to 15-h) half-life. An extended-release formulation is now available for patients on long-term therapy or during the initial titrating phase of an SSRI or TCA. Lorazepam has also been used but is more habituating and results in depression in some patients. Some psychiatrists think that the longer-acting benzodiazepines (eg, diazepam, clonazepam) also have advantages.

Benzodiazepine dependence occurs in as many as 30% of long-term users (>8 wk). Many think that after 6 months they should be slowly tapered (over several weeks to months) to avoid withdrawal and precipitating panic. Withdrawal symptoms include anxiety, insomnia, tremor, impaired concentration, lethargy, dysphoria, headaches, gastrointestinal disturbances, dizziness, photophobia, and hyperacusis. Concomitant therapy with TCAs, SSRIs, antiepileptics, or propranolol may be beneficial, although the withdrawal symptoms do not predict success of eventual discontinuation.

Alprazolam (Xanax, Xanax XR)

For management of anxiety attacks. Binds receptors at several sites within the central nervous system, including limbic system and reticular formation. Effects may be mediated through GABA receptor system.

Dosing

Adult

Xanax: 0.25-0.5 mg PO tid; average effective dose 0.5-4 mg/d PO
Xanax XR: 0.5-1 mg qam initially, titrate by 1-mg/d increments over 3-4 d to 3-6 mg/d

Pediatric

<18 years: Not established
>18 years: Administer as in adults

Interactions

Carbamazepine and disulfiram decrease effects; toxicity increases with cimetidine, lithium, contraceptives, ketoconazole or itraconazole (CYP3A4 inhibitors), and CNS depressants (including alcohol)

Contraindications

Documented hypersensitivity; severe respiratory depression; narrow-angle glaucoma; preexisting hypotension

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Withdrawal symptoms, including seizures, may occur upon abrupt discontinuation of drug

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Individualize dosage and increase cautiously to avoid adverse effects.

Dosing

Adult

2-10 mg PO bid/qid

Pediatric

<6 months: Not recommended
>6 months: 1-2.5 mg PO tid/qid initially, increase gradually prn and as tolerated

Interactions

Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohol, and MAOIs

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)

Clonazepam (Klonopin)

Long-acting benzodiazepine that increases the presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). Reaches peak plasma concentration at 2-4 h after oral or rectal administration.

Dosing

Adult

0.5-2 mg PO bid/tid

Pediatric

Not established

Interactions

Phenytoin and barbiturates may reduce effects; coadministration of CNS depressants increase toxicity

Contraindications

Documented hypersensitivity; severe liver disease and acute narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of the medication

Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. This medication is excellent when patient must be sedated for >24-h period.

Dosing

Adult

0.5-1 mg IV/IM or 1-2 mg PO bid/tid
Elderly: Begin with half dose

Pediatric

Not established

Interactions

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAO inhibitors

Contraindications

Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma; reversal agents (eg, flumazenil) contraindicated when lorazepam used for life-threatening conditions (eg, control of intracranial pressure or status epilepticus)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease

Triazolopyridine agents

The mechanism of antidepressant action of this class of drugs is not fully understood in humans. They are not MAOIs and, unlike amphetamine-type drugs, do not stimulate the CNS.

Trazodone (Desyrel)

Useful in the treatment of PD and agoraphobia with panic attacks. Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Also has negligible affinity for cholinergic and histaminergic receptors.
In animals, selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral changes induced by the serotonin precursor, 5-hydroxytryptophan.

Dosing

Adult

Initial: 150 mg/d, may increase by 50 mg/d PO q3-4d; not to exceed 400 mg/d in divided doses; average dose is 300 mg/d
Maintenance: Once an adequate response has been achieved, dosage may be gradually reduced with subsequent adjustment depending on response; keep dose at lowest effective level

Pediatric

<6 years: Not established
>6 years: 1.5-2 mg/kg/d in divided doses initially; increase dose gradually q3-4d prn; not to exceed 6 mg/kg/d

Interactions

May enhance response to alcohol, barbiturates, and other CNS depressants; concurrent use may increase digoxin and phenytoin serum levels; may decrease hypoprothrombinemic effects of warfarin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypotension, including orthostatic hypotension and syncope, has occurred; may produce drowsiness, dizziness, or blurred vision; patients taking this medication should observe caution while driving or performing other tasks requiring alertness, coordination, or dexterity

Selective serotonin reuptake inhibitors

May take from 2-6 weeks to become effective and can result in initial anxiogenic effects, especially with higher doses. Therefore, initial doses should be lower than doses used to treat depression, and they should be titrated up over several weeks. Patients may require concomitant therapy with benzodiazepines for the first several weeks. SSRIs are uniquely effective in PD coexisting with obsessive-compulsive disorder. Sertraline (Zoloft) may be better tolerated than paroxetine (Paxil).¹⁷ Fluvoxamine (Luvox), fluoxetine (Prozac), citalopram (Celexa), and escitalopram (Lexapro) are also effective.¹⁸ Common adverse effects include gastrointestinal problems, headache, dry mouth, insomnia, nervousness, agitation, and difficulty reaching orgasm.

Paroxetine (Paxil) may increase the suicide risk in children and adolescents with major depressive disorder. If paroxetine is discontinued, as with all SSRIs, tapering should occur over several weeks.

Paroxetine (Paxil)

Alternative DOC. Potent selective inhibitor of neuronal serotonin reuptake. Also has a weak effect on norepinephrine and dopamine neuronal reuptake.

Dosing

Adult

Initial: 10 mg/d PO followed by 10-mg/d PO increments prn; dose changes should occur at intervals of at least 1 wk; usual dose range is 10-60 mg/d; not to exceed 60 mg/d
Maintenance: Make dose adjustments to maintain patient on the lowest effective dosage and reassess periodically to determine the need for continued treatment

Pediatric

<18 years: Not established
>18 years: Administer as in adults

Interactions

Phenobarbital and phenytoin decrease effects; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity

Contraindications

Documented hypersensitivity; concurrent administration with MAOIs or administration within 14 d of discontinuing MAOIs

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in history of seizures, mania, renal disease, and cardiac disease

Sertraline (Zoloft)

Selectively inhibits presynaptic serotonin reuptake. Also has a weak inhibitory effect on norepinephrine and dopamine neuronal reuptake.

Dosing

Adult

25 mg PO qd; increase to 50 mg PO qd after 1 wk

Pediatric

Not established

Interactions

Increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in preexisting seizure disorders and in those that have experienced a recent MI, unstable heart disease, and hepatic or renal impairment

Fluvoxamine (Luvox)

Potent selective inhibitor of neuronal serotonin reuptake. Does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and, thus, has fewer adverse effects than tricyclic antidepressants.

Dosing

Adult

50 mg/dose PO hs initially; increase dose in 50-mg increments q4-7d, as tolerated, until maximum therapeutic benefit achieved; divide total daily dose into 2 doses; if doses are unequal, administer larger dose hs; not to exceed 300 mg/d

Pediatric

<8 years: Not established
>8 years: 25 mg PO initially as single daily dose hs; increase dose in 25-mg increments PO q4-7d as tolerated, until maximum therapeutic benefit achieved; divide total daily doses >50 mg into 2 doses; if not equal, administer larger dose hs; not to exceed 200 mg/d

Interactions

Risk of a hypertensive crisis increases with coadministration with MAOIs; potentiates effect of triazolam and alprazolam, and thus, when taking them concurrently, dose should be reduced by at least 50%; also reduce the dose of theophylline by one third and monitor plasma levels if taking concurrently with fluvoxamine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of fluvoxamine

Contraindications

Documented hypersensitivity; current use of MAOIs or use in previous 2 wk

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver dysfunction, cardiovascular disease, history of seizures, or suicidal tendencies

Fluoxetine (Prozac)

Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine.

Dosing

Adult

5-10 mg/d PO qam; increase after several wk by 20 mg/d; not to exceed 80 mg/d

Pediatric

<18 years: Not established; initial doses of 20 mg/d in children 6-14 y have been used
>18 years: Administer as in adults

Interactions

Increases toxicity of diazepam and trazodone by decreasing clearance; also increases toxicity of MAOIs and highly protein bound drugs

Contraindications

Documented hypersensitivity; use of MAOIs or use in the last 2 wk

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hepatic impairment and history of seizures; MAOIs should be discontinued at least 14 d before initiating therapy

Tricyclic antidepressants

These agents have the advantages of once daily dosing, low risk of dependence, and no dietary restrictions. However, they are discontinued in 35% of cases because of adverse effects, such as blurred vision, dry mouth, dizziness, weight gain, gastrointestinal disturbance, agitation, insomnia, headache, and decreased libido or ability to orgasm. TCAs must be started in low doses to avoid amphetaminelike stimulation and can require up to 8-12 weeks for treatment response.

Imipramine (Tofranil)

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron.
Use parenteral administration for starting therapy only in patients unable or unwilling to use PO medication.

Dosing

Adult

10 mg/d PO increasing by 10 mg q2-4d for 2 wk, then by 25 mg q2-3d to 100 mg/d hs; up to 100 mg/d IM divided tid/qid; change to PO route as soon as possible

Pediatric

Not established; recommended dose is 1.5 mg/kg/d PO, with dosage increments of 1 mg/kg q3-4d; not to exceed 5 mg/kg qd or divided bid/qid
Adolescents: 25-50 mg/d PO initially with dosage increased by increments prn; not to exceed 100 mg/d

Interactions

Increases toxicity of sympathomimetic agents, such as isoproterenol and epinephrine, by potentiating effects and inhibiting antihypertensive effects of clonidine

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; acute recovery phase following myocardial infarction; current use of MAOIs or fluoxetine or use in the previous 2 wk

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, or receiving thyroid replacement

Desipramine (Norpramin)

May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation or serotonin receptors.

Dosing

Adult

10-250 mg/d PO

Pediatric

Not established

Interactions

Decreases antihypertensive effects of clonidine but increases effects of sympathomimetics and benzodiazepines; effects increase with phenytoin, carbamazepine, and barbiturates

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; recent postmyocardial infarction; current use of MAOIs or fluoxetine or use in the previous 2 wk

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and patients receiving thyroid replacement

Clomipramine (Anafranil)

Affects serotonin uptake while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine.

Dosing

Adult

25-100 mg/d PO

Pediatric

Not established

Interactions

Barbiturates, phenytoin, and carbamazepine decrease effects; increases effects of anticholinergics, sympathomimetics, alcohol, and CNS depressants; toxicity of MAOIs increases

Contraindications

Documented hypersensitivity; recent MI; use of MAOIs within 14 d

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in severe cardiopulmonary or renal impairment and in persons unable to metabolize sorbitol

Monoamine oxidase inhibitors

They are effective in patients with social phobia. Advantages of MAOIs are low risk of dependence and less anticholinergic effect than TCAs. Disadvantages are the higher number of adverse effects, including sexual difficulty, hypotension, weight gain, dry mouth, tachycardia, insomnia, drowsiness, headache, weakness, and constipation.

Phenelzine (Nardil)

MAOI most commonly used for PD. Has demonstrated clear superiority over placebo in double-blind trials for treating specific symptoms of PD. Usually reserved for patients who do not tolerate or respond to traditional cyclic or second-generation antidepressants.

Dosing

Adult

15 mg PO divided tid initially; increase gradually to 60-90 mg/d prn during early phase of treatment; after maximum benefit, reduce dosage slowly over several wk
15 mg/d or qod maintenance; may continue taking medication for as long as required

Pediatric

<16 years: Not recommended
>16 years: Administer as in adults

Interactions

Increases effects and/or toxicity of barbiturates and CNS depressants; toxicity increases when taken concurrently with fluoxetine, disulfiram, levodopa, sympathomimetics, and tyramine-containing foods

Contraindications

Documented hypersensitivity; pheochromocytoma; hepatic or renal disease; cardiovascular disease; cerebrovascular defect

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperactive or hyperexcitable disorders and glaucoma

Tranylcypromine (Parnate)

Also effective in PD. Binds irreversibly to MAO, thereby reducing monoamine breakdown and enhancing synaptic availability.

Dosing

Adult

30-60 mg/d PO

Pediatric

Not established

Interactions

Increases effects and/or toxicity of barbiturates and CNS depressants; toxicity increases when taken concurrently with fluoxetine, disulfiram, levodopa, sympathomimetics, and tyramine-containing foods

Contraindications

Documented hypersensitivity; pheochromocytoma; hepatic or renal disease; cardiovascular disease; cerebrovascular defect

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperactive or hyperexcitable disorders and glaucoma

Follow-up

Further Inpatient Care

• Inpatient treatment is necessary in patients with suicidal ideation and plan, serious alcohol or sedative withdrawal symptoms, or when the differential includes other medical disorders that warrant admission (eg, unstable angina, acute myocardial ischemia).
  

Further Outpatient Care

• Follow-up care by a chemical dependence treatment specialist is recommended when indicated.
• Patients with ventricular dysrhythmias, abnormal findings on ECG, abnormal findings on cardiac examination, or significant risk factors for heart disease should be referred to a cardiologist.
• All patients with PD should be referred to a psychiatrist, psychologist, or other mental health professional. Free information is available to patients and physicians from the National Institute of Mental Health (NIMH) by calling 1-800-64-PANIC or by writing to the following address: NIMH
  Room 7C-02
  5600 Fishers Ln
  Rockville, MD 20857
• Cognitive behavioral therapy (CBT), with or without pharmacotherapy, is the treatment of choice, and it should be considered for all patients.¹⁹ CBT has higher efficacy and lower cost, dropout rates, and relapse rates than pharmacological treatments. CBT in combination with pharmacotherapy is more effective than either alone.²⁰
  • Patients meet with therapists for 1-3 hours per week for at least 8-12 weeks.
  • Cognitive restructuring involves substituting positive thoughts (eg, patients can tell themselves that they are only feeling a little uneasiness or that their feelings will soon be gone) for the maladaptive thoughts that accompany panic (eg, feeling that they are going to die or are having a heart attack).
  • Behavioral therapy involves various relaxation techniques and breathing retraining. Guided imagery and hypnotic suggestion may also be beneficial.
  • Capnometry feedback-assisted breathing training therapy can be used to prevent hypocapnia and stabilize the respiratory rate.
  • Interoceptive exposure involves encouraging patients to induce internal sensations (eg, dizziness, increased heart rate, lightheadedness) by spinning, exercising, or rapid breathing and to interpret these as normal bodily sensations.
  • Instructions for finding a cognitive behavioral therapist can be found at Paniccure.com.

Inpatient & Outpatient Medications

• Although pharmacotherapy for panic disorder should generally be deferred to the follow-up psychiatrist, in a very limited subset of patients with panic disorder in the ED, alprazolam (Xanax) as an abortive and/or prophylactic agent may be instituted for a brief course of treatment (generally 1-3 days, recommend no longer than 1 wk)
• Most patients are started on long-term (eg, 6 mo) therapy with SSRIs, TCAs, or MAOIs only after consultation with their primary physician or psychiatrist.

Transfer

• Transfer to an acute psychiatric facility may be necessary for suicidal or homicidal patients.

Deterrence/Prevention

• CBT with cognitive restructuring, relaxation techniques, breathing exercises, hypnotic suggestion, and interoceptive exposure may prevent recurrence.
• Pharmacotherapy and dietary modification (eg, 5-hydroxytryptophan or inositol supplementation) may prevent recurrence.
• Exercise is effective in preventing panic recurrence.
• Patients who have give a high importance to religion and religious practices have improved panic symptoms and fewer recurrences.
• Internet-based cognitive behavioral therapy and virtual reality exposure therapy are promising.

Complications

• Patients with panic disorder are reluctant to believe their symptoms are not life threatening and have a high rate of ED use if education, treatment, and follow-up care are incomplete.
• Because of a reluctance to use medications (related to a fear of losing control), patients with panic disorder are frequently noncompliant. Patients with panic disorder also have a 4-fold increased risk of medication adverse effects.
• Benzodiazepine abuse is rare. It is less likely to occur in patients without history of chemical dependence or emotional dependence.
  • Benzodiazepine abuse is suggested by escalating dose consumption over time.
  • Because panic disorder is usually a chronic disorder, sole reliance on habituating drugs (benzodiazepines) is discouraged.
  • Benzodiazepine dependence can occur in 30% of patients on long-term therapy longer than 8 weeks.
  • Benzodiazepine withdrawal can precipitate panic. The primary physician should gradually taper doses over several weeks or months.
• Individuals with panic disorder have a suicide rate 18 times higher than the population.
• The rate of substance abuse (especially stimulants, cocaine, and hallucinogens) in persons with panic disorder is 7-28%, a risk 4-14 times greater than that of the population.
• Pregnant mothers with panic disorder are more likely to have infants of smaller birth weight for gestational age.
• Panic patients are nearly twice as likely to develop coronary artery disease, and those with known coronary disease can experience myocardial ischemia during their panic episodes.^21,22

Prognosis

• Long-term prognosis is usually good, although the risk of coronary artery disease is nearly doubled. In patients with coronary disease, panic can induce myocardial ischemia.²² The risk of sudden death may also theoretically be increased due to reduced heart rate variability and increased QT interval variability.
• Appropriate pharmacological therapy and cognitive-behavioral therapy, individually or in combination, are effective in more than 85% of cases.

Patient Education

• Information regarding panic disorder and support groups can be obtained from the NIMH (see Further Outpatient Care).
• Advise patients with panic disorder to avoid nicotine, sympathomimetic or anticholinergic drugs, caffeine, and alcohol.
• Dietary modification (eg, 5-hydroxytryptophan or inositol supplementation) may be effective in preventing recurrence. Such herbal supplementation should be deferred until after the patient has discussed it with the psychiatrist or primary care provider that is responsible for the follow-up and long-term care of the patient.
• For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center and Anxiety Center. Also, see eMedicine's patient education articles Panic Attacks, Anxiety, and Palpitations.

Miscellaneous

Medicolegal Pitfalls

• Persons with panic disorder are no less likely (and perhaps even twice as likely) to have coronary artery disease than the general population.
• Approximately 44% of ED patients with panic disorder have a history of coronary disease.
• Exclude acute coronary syndromes in patients with risk factors, history, and ECG findings before labeling the event as panic.
• Patients with supraventricular tachycardia have the potential to be misclassified as having panic disorder (in more 50% of cases), and panic disorder may be missed if event monitoring is not obtained.
• As many as 10-20% of patients with panic disorder have had a suicide attempt.
• As many as 7-28% of patients with panic disorder have a history of substance abuse.
• Many of the symptoms of an anxiety attack correspond with symptomatology found in life-threatening medical disorders (eg, pulmonary embolus). Remember that panic disorder is a diagnosis of exclusion.
• Patients with panic disorder are twice as likely as the population to use alternative therapies. Use of dietary supplements (eg, herbs) should be discussed to avoid drug interactions.

References

1. Warshaw MG, Dolan RT, Keller MB. Suicidal behavior in patients with current or past panic disorder: five years of prospective data from the Harvard/Brown Anxiety Research Program. Am J Psychiatry. Nov 2000;157(11):1876-8. [Medline].

2. Wedekind D, Bandelow B, Broocks A, et al. Salivary, total plasma and plasma free cortisol in panic disorder. J Neural Transm. 2000;107(7):831-7. [Medline].

3. Neumeister A, Bain E, Nugent AC. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. Jan 21 2004;24(3):589-91. [Medline].

4. Johnson MR, Lydiard RB, Ballenger JC. Panic disorder. Pathophysiology and drug treatment. Drugs. Mar 1995;49(3):328-44. [Medline].

5. Dratcu L. Panic, hyperventilation and perpetuation of anxiety. Prog Neuropsychopharmacol Biol Psychiatry. Oct 2000;24(7):1069-89. [Medline].

6. Vythilingam M, Anderson ER, Goddard A, et al. Temporal lobe volume in panic disorder--a quantitative magnetic resonance imaging study. Psychiatry Res. Aug 28 2000;99(2):75-82. [Medline].

7. Lee HB, Hening WA, Allen RP, Kalaydjian AE, Earley CJ, Eaton WW, et al. Restless legs syndrome is associated with DSM-IV major depressive disorder and panic disorder in the community. J Neuropsychiatry Clin Neurosci. Winter 2008;20(1):101-5. [Medline].

8. Kaiya H, Sugaya N, Iwasa R, Tochigi M. Characteristics of fatigue in panic disorder patients. Psychiatry Clin Neurosci. Apr 2008;62(2):234-7. [Medline].

9. Schmidt NB, Lerew DR, Santiago H, et al. Effects of heart-rate feedback on estimated cardiovascular fitness in patients with panic disorder. Depress Anxiety. 2000;12(2):59-66. [Medline].

10. Sullivan GM, Kent JM, Kleber M. Effects of hyperventilation on heart rate and QT variability in panic disorder pre- and post-treatment. Psychiatry Res. Jan 30 2004;125(1):29-39. [Medline].

11. Fleet RP, Martel JP, Lavoie KL, et al. Non-fearful panic disorder: a variant of panic in medical patients?. Psychosomatics. Jul-Aug 2000;41(4):311-20. [Medline].

12. Katerndahl DA, Talamantes M. A comparison of persons with early-versus late-onset panic attacks. J Clin Psychiatry. Jun 2000;61(6):422-7. [Medline].

13. Dannon PN, Lowengrub K, Amiaz R. Comorbid cannabis use and panic disorder: short term and long term follow-up study. Hum Psychopharmacol. Mar 2004;19(2):97-101. [Medline].

14. Schifano F, Di Furia L, Forza G, et al. MDMA ('ecstasy') consumption in the context of polydrug abuse: a report on 150 patients. Drug Alcohol Depend. Sep 1 1998;52(1):85-90. [Medline].

15. Ballenger JC, Davidson JR, Lecrubier Y, et al. Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry. 1998;59 Suppl 8:47-54. [Medline].

16. Baldwin DS, Birtwistle J. The side effect burden associated with drug treatment of panic disorder. J Clin Psychiatry. 1998;59 Suppl 8:39-44; discussion 45-6. [Medline].

17. Bandelow B, Behnke K, Lenoir S. 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].

18. Bakker A, van Balkom AJ, van Dyck R. Selective serotonin reuptake inhibitors in the treatment of panic disorder and agoraphobia. Int Clin Psychopharmacol. Aug 2000;15 Suppl 2:S25-30. [Medline].

19. Cloos JM. The treatment of panic disorder. Curr Opin Psychiatry. Jan 2005;18(1):45-50. [Medline].

20. [Best Evidence] Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: systematic review. Br J Psychiatry. Apr 2006;188:305-12. [Medline].

21. Gomez-Caminero A, Blumentals WA, Russo LJ. Does panic disorder increase the risk of coronary heart disease? A cohort study of a national managed care database. Psychosom Med. Sep-Oct 2005;67(5):688-91. [Medline].

22. Fleet R, Lesperance F, Arsenault A, et al. Myocardial perfusion study of panic attacks in patients with coronary artery disease. Am J Cardiol. Oct 15 2005;96(8):1064-8. [Medline].

23. Clum GA, Clum GA, Surls R. A meta-analysis of treatments for panic disorder. J Consult Clin Psychol. Apr 1993;61(2):317-26. [Medline].

24. Davidson JR. The long-term treatment of panic disorder. J Clin Psychiatry. 1998;59 Suppl 8:17-21; discussion 22-3. [Medline].

25. den Boer JA. Pharmacotherapy of panic disorder: differential efficacy from a clinical viewpoint. J Clin Psychiatry. 1998;59 Suppl 8:30-6; discussion 37-8. [Medline].

26. Fleet RP, Dupuis G, Marchand A, et al. Panic disorder in emergency department chest pain patients: prevalence, comorbidity, suicidal ideation, and physician recognition. Am J Med. Oct 1996;101(4):371-80. [Medline].

27. Fleet RP, Marchand A, Dupuis G, et al. Comparing emergency department and psychiatric setting patients with panic disorder. Psychosomatics. Nov-Dec 1998;39(6):512-8. [Medline].

28. Hofmann SG, Spiegel DA. Panic control treatment and its applications. J Psychother Pract Res. 1999;8(1):3-11. [Medline].

29. Katerndahl DA. Panic attacks and panic disorder. J Fam Pract. Sep 1996;43(3):275-82. [Medline].

30. Kjernisted K, McIntosh D. Venlafaxine extended release (XR) in the treatment of panic disorder. Ther Clin Risk Manag. Mar 2007;3(1):59-69. [Medline].

31. Loerch B, Graf-Morgenstern M, Hautzinger M, et al. Randomised placebo-controlled trial of moclobemide, cognitive-behavioural therapy and their combination in panic disorder with agoraphobia. Br J Psychiatry. Mar 1999;174:205-12. [Medline].

32. Margraf J, Barlow DH, Clark DM, et al. Psychological treatment of panic: work in progress on outcome, active ingredients, and follow-up. Behav Res Ther. Jan 1993;31(1):1-8. [Medline].

33. Michelson D, Pollack M, Lydiard RB, et al. Continuing treatment of panic disorder after acute response: randomised, placebo-controlled trial with fluoxetine. The Fluoxetine Panic Disorder Study Group. Br J Psychiatry. Mar 1999;174:213-8. [Medline].

34. Michelson LK, Marchione K. Behavioral, cognitive, and pharmacological treatments of panic disorder with agoraphobia: critique and synthesis. J Consult Clin Psychol. Feb 1991;59(1):100-14. [Medline].

35. Otto MW, Pollack MH, Maki KM. Empirically supported treatments for panic disorder: costs, benefits, and stepped care. J Consult Clin Psychol. Aug 2000;68(4):556-63. [Medline].

36. Pohl RB, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double-blind multicenter trial. Am J Psychiatry. Sep 1998;155(9):1189-95. [Medline].

37. Rickels K, Schweizer E. Panic disorder: long-term pharmacotherapy and discontinuation. J Clin Psychopharmacol. Dec 1998;18(6 Suppl 2):12S-18S. [Medline].

38. Roy-Byrne P, Stein M, Bystrisky A, et al. Pharmacotherapy of panic disorder: proposed guidelines for the family physician. J Am Board Fam Pract. Jul-Aug 1998;11(4):282-90. [Medline].

39. Roy-Byrne PP. Integrated treatment of panic disorder. Am J Med. Jan 24 1992;92(1A):S. [Medline].

40. Roy-Byrne PP, Stein MB, Russo J, et al. Panic disorder in the primary care setting: comorbidity, disability, service utilization, and treatment. J Clin Psychiatry. Jul 1999;60(7):492-9; quiz 500. [Medline].

Keywords

panic disorder, panic attack, panic attacks, anxiety attack, mood disorder, nonfearful panic disorder, NFPD, anxiety disorders, agoraphobia, psychiatric disorder, PD

Contributor Information and Disclosures

Author

Michael C Plewa, MD, Research Coordinator, Consulting Staff, Department of Emergency Medicine, Lucas County Emergency Physicians, Inc, and Saint Vincent Mercy Medical Center
Michael C Plewa, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Physicians for Social Responsibility, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Samuel M Keim, MD, Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine
Samuel M Keim, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Public Health Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Robert Harwood, MD, MPH, FACEP, FAAEM, Program Director, Department of Emergency Medicine, Advocate Christ Medical Center; Assistant Professor, Department of Emergency Medicine, University of Illinois at Chicago College of Medicine
Robert Harwood, MD, MPH, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School
Jonathan Adler, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Clinical guidelines

Practice guideline for the treatment of patients with panic disorder, second edition. Work Group on Panic Disorder. American Psychiatric Association. 2009

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)