Panic Disorder 

Updated: Mar 21, 2018



Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks, the frequency of which can vary from several attacks per day to only a few attacks per year. Panic attacks are defined as a period of intense fear in which 4 of 13 defined symptoms develop abruptly and peak rapidly less than 10 minutes from symptom onset. (See History.) Although such attacks can occur in other anxiety disorders, these attacks often occur without a discernible predictable precipitant in panic disorder. (See Diagnostic Considerations and Workup.)

To meet the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition (DSM-5)[1] criteria for panic disorder, panic attacks must be associated with longer than 1 month of subsequent persistent worry about: (1) having another attack or consequences of the attack, or (2) significant maladaptive behavioral changes related to the attack. To make the diagnosis of panic disorder, panic attacks cannot directly or physiologically result from substance use (intoxication or withdrawal), medical conditions, or another psychiatric disorder. (See History.) Other symptoms or signs may include headache, cold hands, diarrhea, insomnia, fatigue, intrusive thoughts, and ruminations. (See Physical Examination.)

Following exclusion of somatic disease, substance use disorders, and other psychiatric disorders, confirmation of the diagnosis of panic disorder with a brief mental status screening examination and initiation of appropriate treatment and referral is time- and cost-effective in patients with this condition, who have high rates of medical resource use. (See Mental Status Examination.)

Consequences of panic disorder

Panic disorder can lead to a significant hindrance in lifestyle. Individuals with panic disorder also may face problems with employment and depression.[2]

In addition, persons with panic disorder have a much higher risk of alcohol abuse or dependence and suicidality than the general population.[2] However, 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 use disorders, eating disorders, and personality disorders.[3]

For more information, see the Medscape Reference topics Anxiety Disorders; Specific Phobia; Separation Anxiety and School Refusal; and Phobic Disorders.


Etiologic theories

The apparent neurochemical dysfunction behind panic disorder may involve autonomic imbalance, decreased gamma-aminobutyric acid (GABA)–ergic tone,[13] allelic polymorphism of the catechol-O-methyltransferase (COMT) gene, increased adenosine receptor function, increased cortisol,[14] diminished benzodiazepine receptor function, and disturbances in serotonin,[15] serotonin transporter (5-HTTLPR)[16] and promoter (SLC6A4) genes,[17] norepinephrine, dopamine, cholecystokinin, and interleukin 1–beta.[18]

Some authors theorize that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor hypersensitivity.[8] Some epileptic patients have panic as a manifestation of their seizures.

The serotonergic model suggests an exaggerated or inefficient postsynaptic receptor response to synaptic serotonin, potentially in the signal transduction cascade. Some studies report subsensitivity of serotonin 1A (5HT1A) receptors. The 5HT system or one of its subsystems may play a role in the pathophysiology of panic disorder, but further investigation is needed.

The catecholamine model postulates increased sensitivity to or improper processing of adrenergic CNS discharges, with potential hypersensitivity of presynaptic alpha-2 receptors.

Similarly, the locus coeruleus model explains that panic symptoms are due to increased local discharge resulting in adrenergic neuronal stimulation, similar to the more general catecholamine theory. Locus coeruleus activity also affects the hypothalamic-pituitary-adrenal (HPA) 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, hypothalamus, and brainstem centers. More generally, the corticostriatal-thalamocortical (CSTC) circuitry is believed to mediate worry, interacting with the more fear-specific circuit in the amygdala. The sensation of fear occurs through reciprocal regulatory activity conceptually initiated in the amygdala and projected to the anterior cingulate cortex and/or orbitofrontal cortex. Projections from the amygdala to the hypothalamus then mediate endocrinologic responses to fear.

The cognitive theory suggests that patients with panic disorder have a heightened sensitivity to internal autonomic cues (e.g., tachycardia).

Genetic factors

Panic disorder is a common psychiatric disorder that affects 3-5% of the population.[61] Studies of the association between psychiatric illness in first-degree relatives revealed a heredity of approximately 43% for panic disorder.[42] Patients with panic disorder also have a high rate (80%) of having other psychiatric disorders, many of which also have an important genetic basis.

Although panic disorder is a disease with a significant genetic basis, the exact nature of the basis is unclear. The present understanding suggests that panic disorder is a multifactorial condition, with multiple genes creating susceptibility to the condition coupled with influences from the environment.[54] The genetics of panic disorder is poorly understood relative to many psychiatric disorders in which genome-wide association studies (GWAS) have isolated numerous loci associated with susceptibility to disease.

Nonetheless, there are several loci that have been implicated in families with a strong history of panic disorder. Locus 13q22-32 has been linked to panic disorder and bladder conditions in families although the association was not found in families who had isolated panic disorder.[43] A locus at 9q31 was found to be associated with panic disorder (and likely generalized anxiety disorder) for an Icelandic cohort.[44]

In a study that performed a genome scan looking for regions of interest for anxiety disorders broadly defined in 219 US subjects in 19 extended pedigrees, investigators found an association at marker D4S413 on chromosome 4q31-q34, which is located near the NPY1R gene. This gene encodes the neuropeptide Y 1 receptor, and in an animal model, manipulation of this receptor was associated with anxiolysis.[45] A large GWAS that looked mainly at bipolar disorder but also psychosis, panic disorder, and suicidal behavior found an associated locus for panic disorder on 7q21.[47, 52]

Further study has implicated a few genes as likely contributors to panic disorder. Because monoamine oxidase inhibitors (MAOIs) have been used effectively in the treatment of panic disorder, the MAOA (monoamine oxidase A) gene is a logical consideration for contribution to panic disorder. In a study of a German and Italian population, patients with a longer repeat polymorphism in the MAOA promoter region had a higher incidence of panic disorder.[59] In recent years, the use of MAOIs has been in large part supplanted by newer agents.

Persons who are homozygous for a polymorphism in the COMT gene (catechol-o-methyltransferase), in which a methionine substitutes for a valine at position 158, have been associated with a higher rate of panic disorder than persons who did not carry these polymorphisms.[46] Additionally, it has been suggested that people who were homozygous for this polymorphism also had a poorer response to treatment.[46] A different study of the same polymorphism found an increased benefit of exposure-based therapy for those who had the Val158Met polymorphism.[53]

More recently, studies have isolated additional genes of interest for panic disorder. A polymorphism on the HCRT (hypocretin) gene, in which isoleucine substitutes for valine at position 308 on 17q21.2, has been implicated in increased risk of panic disorder.[48] Additional GWAS have identified the neuropeptide S gene, the amiloride-sensitive cation channel gene, and the adenosine A(2A) genes as candidate genes.[49, 50, 51]


Lifetime prevalence estimates for panic disorder in US adults range from 2.0% to 6.0%.[61] The 12-month prevalence in adults is 2.7%, of which 44.8% are classified as “severe” cases.[61]

Panic disorder often coexists with mood disorders, and mood symptoms potentially follow the onset of panic attacks. Lifetime prevalence rates of major depression in panic disorder may be as high as 50-60%.[63] Other psychiatric disorders that occur comorbidity with panic disorder include schizophrenia, obsessive-compulsive disorder, specific phobias, social phobia, and agoraphobia.[60]

There are also medical conditions that apparently share significant comorbidity with panic disorder, such as COPD, irritable bowel syndrome, migraine headache, restless leg syndrome, and fatigue.[20, 21] Cardiovascular disorders (e.g., mitral valve prolapse, hypertension, cardiomyopathy, stroke) are also comorbid factors[22] ; panic patients are nearly twice as likely to develop coronary artery disease. Patients with both panic disorder and coronary disease can experience myocardial ischemia during their panic episodes[23, 24] ; thus, panic disorder is also associated with a higher risk of sudden death.[25] In addition, panic disorder is also present in 30% of patients with chest pain and normal findings on angiography, and individuals with panic disorder tend to have lower oxygen consumption and exercise tolerance than does the general population.[26]

Asthma is linked to a 4.5-fold increase in the risk of developing panic disorder, and people with panic disorder are 6 times as likely as those without anxiety disorders to develop asthma.[64] Patients with panic disorder can also have migraine headaches (12.7%), tension headaches (5.5%), and combined migraine and tension headaches (14.2%).[65] The lifetime prevalence of panic disorder in people with epilepsy is 6.6%.[66]

Approximately 10-20% of patients with anxiety disorder abuse alcohol and other drugs, and about 10-40% of alcoholics have a panic-related anxiety disorder.[67]

Pregnant mothers with panic disorder during pregnancy are more likely to have preterm labor and infants of smaller birth-weight for gestational age.[27]

Racial, sexual, and age-related differences

Prevalence data for different racial groups are inconsistent. Symptom manifestations may differ, with black persons more often presenting with somatic symptoms and more likely to seek help in medical rather than psychiatric settings.

Women are 2-3 times more likely to be affected than men. Panic is also more common in women who have never been pregnant and during the postpartum period; it is less common during pregnancy.

Although panic can occur in people at any age, it usually develops between the ages of 18 and 45 years, with an average age of onset of 24 years.[61] Patients with late-onset panic disorder have a tendency toward less use of mental health resources, have lower comorbidity and hypochondriasis, and have better coping behavior.[28]


Panic disorder is a chronic disorder with a variable course. Appropriate pharmacologic therapy and cognitive-behavioral therapy (CBT), individually or in combination, are effective in more than 85% of cases. Patients with good premorbid functioning and a brief duration of symptoms tend to have a good prognosis.[68] About 10-20% of patients continue to have significant symptoms.[68]

Overall, the long-term prognosis is usually good, with almost 65% of patients with panic disorder achieving remission, typically within 6 months.[29] However, as discussed under History, trigger factors can lead to panic attacks— several of these triggers are associated with poor outcome, including severe illness at the time of the initial assessment, high interpersonal sensitivity, low social class, separation from a parent by death during early life, divorce, and unmarried status.[62]

The risk of coronary artery disease in patients with panic disorder is nearly doubled. In patients with coronary disease, panic can induce myocardial ischemia.[24] The risk of sudden death may also theoretically be increased due to reduced heart rate variability and increased QT interval variability.[25]

The suicide rate in individuals with panic disorder is also many times higher than the general population.[2]

Patient Education

Inform patients that the causes of panic disorder are likely biologic and psychosocial, and that panic symptoms are not life-threatening or uncommon.[55]

Educate patients about their diagnosis and treatment options, as well as about potential adverse effects of not only their treatment medications but also any comorbid substance use such as alcohol consumption and recreational drug use. These psychoactive substances can impact the course of panic disorder. Although some substances may seem to avert the anguish of an acute attack, they often compromise the long-term treatment plan.

Consider educating patients diagnosed with panic disorder about cognitive distortions that may help to amplify anxiety. Teach patients to recognize trigger stimuli so that they can contribute this to their psychological treatment approach.

Obtain verbal informed consent for psychotropic medications, and document the discussion of the risks and benefits of treatment medications. Promote healthy behaviors, including exercise and good sleep hygiene. Advise patients to avoid anxiogenic substances, such as caffeine, energy drinks, and other OTC stimulants.[55]

Talk to the patient’s family about the importance of minimizing any avoidance behaviors by the patient and ensuring pharmacologic compliance and adherence to therapy appointments. Help the family to understand the nature of the anxiety symptoms and to provide reasonable accommodation (without enabling dysfunctional behaviors or alcohol/prescription drug use). Family members can be particularly important in helping the patient to overcome unrealistic fears and ingrained avoidance behaviors, in the context of ongoing cognitive-behavioral therapy (CBT) in which the patient learns the coping skills to manage anxiety.

Although dietary modification (eg, 5-hydroxytryptophan or inositol[30] supplementation) may be effective in preventing recurrence, there is much more evidence for the effectiveness of CBT and medications. Herbal supplementation should be deferred until after the patient has discussed it with his or her psychiatrist or primary care provider.

For more information, see Anxiety Center, as well as Anxiety, Panic Attacks, and Hyperventilation.




A general medical evaluation is important to rule out medical causes of panic symptoms.[55, 56] History, collateral information, and physical examination, as well as a mental status examination remain the diagnostic cornerstones for panic disorder. It is crucial to assess the specific features of the individual patient’s panic disorder, such as whether agoraphobia is present, the extent of situational fear and avoidance, and whether there are comorbid psychiatric conditions, all of which can affect the course, treatment, and prognosis of panic disorder.[55, 56]


DSM-5 criteria for panic disorder 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 panic attack.[1]

The following are potential symptom manifestations of a panic attack[1] :

  • 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

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).

Patients with panic disorder have recurring episodes of panic, with the fear of recurrent attacks resulting in significant behavioral changes (e.g., avoiding certain situations or locations) and worry about the implications or consequences of the attack (e.g., losing control, going crazy, dying). Panic disorder may result in changes in personality traits, characterized by the patient becoming more passive, dependent, or withdrawn.

Types of panic attacks

Unexpected panic attacks have no known precipitating cue. Situationally-bound (cued) panic attacks recur predictably in temporal relationship to the trigger; these panic attacks usually implicate the diagnosis of a specific phobia. Situationally predisposed panic attacks are more likely to occur in relation to a given trigger, but they do not always occur.

A variant of panic disorder unrelated to fear (nonfearful panic disorder [NFPD]) is associated with high rates of medical resource use (32-41% of patients with panic disorder seeking treatment for chest pain) and a poor prognosis.[4]

Panic triggers

Triggers of panic can include the following:

  • Injury (e.g., accidents, surgery)

  • Illness

  • Interpersonal conflict or loss

  • Use of cannabis (can be associated with panic attacks[5] ; the associated anxiety/panic may be due to the direct physiologic effects of cannabis use)

  • Use of stimulants, such as caffeine, decongestants, cocaine, and sympathomimetics (e.g., amphetamine, methylenedioxymethamphetamine [MDMA, ecstasy])[6]

  • The selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome, which can induce symptoms similar to those experienced by panic patients

Assess precipitating events (e.g., major life events), phobias, agoraphobia, obsessive-compulsive behavior, and suicidal ideation and/or plan. In one study, lifetime rates of suicide attempts in patients with uncomplicated panic disorder were consistently higher (7%) than in individuals without a psychiatric disorder (1%).[69] Also assess whether there is a family history of panic or other psychiatric illness.

Exclude involvement of alcohol, nicotine, illicit drugs (e.g., cocaine, amphetamine, phencyclidine, amyl nitrate, lysergic acid diethylamide [LSD], yohimbine, 3,4-methylenedioxymethamphetamine [MDMA, ecstasy]), cannabis, and medications (e.g., caffeine, theophylline, sympathomimetics, anticholinergics), including OTC agents.

In experimental settings, symptoms can be elicited in people with panic disorder by hyperventilation, inhalation of carbon dioxide,[8] caffeine consumption, or intravenous infusions of hypertonic sodium lactate or hypertonic saline,[9] cholecystokinin, isoproterenol, flumazenil, or naltrexone.[10] The carbon dioxide inhalation challenge is especially provocative of panic symptoms in smokers.[11]

Physical Examination

There are no physical signs specific for panic disorder. 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, mild tremors, and cool, clammy skin. Blood pressure and temperature may be within the reference range. A panic attack normally lasts 20-30 minutes from onset, although in rare cases it can go on for 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.

Hyperventilation may be difficult to detect by observing breathing, because respiratory rate and tidal volume may appear normal. Patients may sigh frequently or have difficulty with breath-holding. Reproduction of symptoms with overbreathing is unreliable. Chvostek sign, Trousseau sign, or overt carpopedal spasm may be present.

The remaining physical 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.

Mental Status Examination

No results on the mental status examination are specific for panic disorder. The patient may or may not appear anxious at the time of interview, and the results on his or her Mini-Mental Status Examination, including cognitive performance, memory, serial-7, and proverb interpretation, should appear intact and consistent with the patient’s educational level and apparent baseline intellectual functioning.

During a panic attack, a mental status examination may reveal extreme anxiety, fear, and a sense of impending death or doom. The patient may have difficulty speaking as well as appear sweaty and confused. The patient’s speech may reflect anxiety or urgency, or it may sound normal, and the individual’s mood may be described as similar to "anxious," with congruent affect. Incongruent affect should raise consideration of other diagnostic possibilities.

The patient’s thought processes should be logical, linear, and goal directed. Thought content is particularly important to specifically assess in order to ensure that a patient has no suicidal or homicidal thoughts. Acute anxiety, as a form of acute mental anguish, can lead to unsafe or self-injurious behavior. 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.

Standardized mental status screening tests include the following:

  • Primary Care Evaluation of Mental Disorders (PRIME-MD)

  • The Body Sensations Questionnaire (BSQ)

  • Folstein Mini-Mental Status Examination (MMSE)



Diagnostic Considerations

An understanding of panic disorder is particularly important for emergency physicians, because patients with this condition frequently present to the ED with various somatic complaints. Many of the symptoms of an anxiety attack correspond with symptomatology found in life-threatening medical disorders, such as myocardial infarction (MI) and pulmonary embolus, which may manifest with anxiety as a primary symptom. Approximately 25% of patients who present to an emergency department with chest pain have panic anxiety disorder[70] and few individuals with panic disorder are referred to mental health professionals.

When making a diagnosis, keep in mind the symptomatology of medical conditions such as the following:

  • Angina and myocardial infarction (e.g., dyspnea, chest pain, palpitations, diaphoresis)

  • Cardiac dysrhythmias (e.g., palpitations, dyspnea, syncope)

  • Mitral valve prolapse

  • Pulmonary embolus (e.g., dyspnea, hyperpnea, chest pain)

  • Asthma (e.g., dyspnea, wheezing)

  • Hyperthyroidism (e.g., palpitations, diaphoresis, tachycardia, heat intolerance)

  • Hypoglycemia

  • Pheochromocytoma (e.g., headache, diaphoresis, hypertension)

  • Hypoparathyroidism (e.g., muscle cramps, paresthesias)

  • Transient ischemic attacks (TIAs)

  • Seizure disorder

In addition, consider other mental illnesses that may result in panic attacks, including schizophrenia, bipolar disorder, depressive disorder, posttraumatic stress disorder, phobias, and somatization disorder.

For more information, see the Medscape Reference topics Anxiety Disorders; Separation Anxiety and School Refusal; and Phobic Disorders for more complete information on these topics.

Cardiovascular disease and panic disorder

Persons with panic disorder are no less likely (and are perhaps even twice as likely) to have coronary artery disease than is the general population.[23] In one study, approximately 44% of emergency department patients with panic disorder had a history of coronary disease.[2]

Exclude acute coronary syndromes in patients with risk factors, history, and electrographic findings before labeling the event as panic. Patients with supraventricular tachycardia have the potential to be misdiagnosed with panic disorder in more than 50% of cases; panic disorder may be missed if cardiac event monitoring is not obtained.

Differential Diagnoses



Approach Considerations

No invasive procedures are required to diagnose panic disorder, although they may be useful in eliminating other conditions in the differential diagnosis. As previously mentioned, history, collateral information, physical examination, and a mental status examination remain the diagnostic cornerstones for panic disorder.

Use electrocardiography (ECG) to assess for signs of ventricular preexcitation (short PR and delta wave), for 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 embolism require appropriate testing (e.g., determination of D-dimer level, spiral CT scanning, ventilation-perfusion [V/Q] scanning, duplex Doppler/ultrasonography, or pulmonary angiography).

Diagnostic Studies

Laboratory studies that can exclude medical disorders other than panic disorder include the following:

  • 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, cannabis, cocaine, and phencyclidine in patients suspected of intoxication

  • D-dimer assay to exclude pulmonary embolism

Room air pulse oximetry values are usually 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.

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.

Human subjects with panic anxiety have elevated levels of orexin in the cerebrospinal fluid. Orexin, also known as hypocretin, is thought to play an important role in the pathogenesis of panic in rat models[31] ; it is also a potential gene of risk for panic disorder.

Radiologic 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 electroencephalogram (EEG) to exclude partial complex seizures.

Investigational functional neuroimaging is not used in routine clinical practice for diagnosis or for monitoring treatment response. However, 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.[15] Magnetic resonance imaging (MRI) has demonstrated smaller temporal lobe volume, despite normal hippocampal volume, in patients with panic disorder.[19]



Approach Considerations



  • Tailoring the treatment plan to each individual

  • Reducing frequency and intensity of panic attacks

  • Reducing anticipatory anxiety and agoraphobic avoidance

  • Treating co-occurring psychiatric disorders

  • Achieving full symptomatic remission

  • Returning to premorbid level of function


Cognitive-behavioral therapy




Pharmacologic management



Inpatient vs outpatient care





Emergency Department Management






Cognitive-Behavioral Therapy











SSRIs and TCAs
















Complications of benzodiazepine use



Evaluating Treatment Efficacy and Changes in Treatment Strategy








  • Augment an antidepressant by adding a benzodiazepine to target residual symptoms





Prevention Measures




Treatment Difficulties





Long-Term Monitoring






Medication Summary

First-line pharmacologic therapies for panic disorder include selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs).[55] These 3 classes of agents are preferred over benzodiazepines as monotherapies for patients with co-occurring depression or substance use disorders.

The FDA issued a Drug Safety Communication in August 2011 stating that the SSRI, citalopram (Celexa), should not be used at doses greater than 40 mg per day, owing to the potential for dangerous abnormalities in cardiac electrical activity.[57] Citalopram 20 mg per day is the maximum recommended dose in patients with hepatic impairment, who are older than 60 years, who are CYP 2C19 poor metabolizers, or who are taking concomitant cimetidine (Tagamet) or another CYP 2C19 inhibitor. Such individuals can have higher blood levels of citalopram, leading to an increased risk of prolonged QT interval and torsade de pointes.[57]


For patients requiring rapid symptom control, benzodiazepines can be used as adjuncts with antidepressant agents to treat residual anxiety symptoms, and they may be preferred (as monotherapies or in combination with antidepressants).[55] Clinicians must carefully assess the benefit of more rapid response against the potential complications of benzodiazepine therapy.

The American Psychiatric Association (APA) recommends avoiding TCAs for patients with panic disorder who also have acute narrow-angle glaucoma or clinically significant prostatic hypertrophy.[55] TCAs may increase the risk of falls and fractures, particularly in elderly patients. In addition, owing to the potential for significant or fatal arrhythmia in patients with preexisting cardiac conduction abnormalities, it is important to obtain an electrocardiogram (ECG) in these individuals before starting TCA treatment. Use TCAs with caution in suicidal patients as overdoses with these drugs can cause cardiac toxicity and death.[55]

Anxiolytics, Benzodiazepines

Class Summary

By binding to specific receptor sites, benzodiazepines 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 as-needed (prn) schedules

Lorazepam (Ativan)

Lorazepam is a sedative hypnotic with a short onset of effects and a relatively intermediate half-life. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including the limbic and reticular formations.

Clonazepam (Klonopin)

Clonazepam is a sedative hypnotic that is a long-acting benzodiazepine with a half-life of approximately 36 hours and an intermediate onset of action. This agent facilitates inhibitory GABA neurotransmission and other inhibitory transmitters.

Alprazolam (Xanax, Xanax XR)

Alprazolam is used for the management of anxiety attacks. It is a short-acting anxiolytic with an intermediate onset of effects. This agent binds to receptors at several sites within the CNS, including the limbic system and the reticular formations. The effects of alprazolam may be mediated through the GABA receptor system. Alprazolam has been widely reviewed in the literature, although its use is currently discouraged because of its higher potential to elicit dependency.

Diazepam (Valium, Diastat, Diazepam Intensol)

Diazepam is an anxiolytic benzodiazepine and has a rapid onset of effects. This medication depresses all levels of the CNS (eg, the limbic and reticular formations), possibly by increasing the activity of GABA.

Antidepressants, SSRIs

Class Summary

Selective serotonin reuptake inhibitors (SSRIs) are first-line agents for the long-term management of anxiety disorders. Control is gradually achieved over a 2- to 4-week course, depending on the required dosage increases.

All commonly used SSRIs appear to have a role in the treatment of panic disorder. Fluoxetine is covered here, 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.

Fluoxetine (Prozac)

Fluoxetine selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on reuptake of norepinephrine or dopamine. It has a long half-life and therefore a lower risk of withdrawal symptoms. However, fluoxetine does require slower titration and has CNS stimulating effects.

Paroxetine (Paxil, Paxil CR, Pexeva)

Paroxetine is the least stimulating SSRI. This agent is a potent selective inhibitor of neuronal serotonin reuptake. Paroxetine also has a very weak effect on norepinephrine and dopamine neuronal reuptake. It does not significantly bind to muscarinic, alpha-adrenergic, or histamine receptors and therefore has fewer adverse effects than do tricyclic antidepressants (TCAs).

Sertraline (Zoloft)

Sertraline selectively inhibits presynaptic serotonin reuptake. It also has a very weak inhibitory effect on norepinephrine and dopamine neuronal reuptake.

Fluvoxamine (Luvox, Luvox CR)

Fluvoxamine is a potent selective inhibitor of neuronal serotonin reuptake. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and therefore has fewer adverse effects than do tricyclic antidepressants.

Citalopram (Celexa)

Citalopram enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. SSRIs are the antidepressants of choice due to minimal anticholinergic effects.

Escitalopram (Lexapro)

Escitalopram is an SSRI and an S-enantiomer of citalopram. Its mechanism of action is thought to be potentiation of serotonergic activity in the CNS resulting from the inhibition of CNS neuronal reuptake of serotonin.

Antidepressants, TCA

Class Summary

Tricyclic antidepressants (TCAs) have the advantages of once-daily dosing, low risk of dependence, and no dietary restrictions. However, these drugs are discontinued in 35% of patients 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 amphetamine-like stimulation and can require up to 8-12 weeks for treatment response.

Imipramine (Tofranil, Tofranil-PM)

The mechanism of action of imipramine is not fully known. However, the clinical effect is hypothesized as being due to the inhibition of the reuptake of norepinephrine and serotonin (5-hydroxytryptamine [5-HT]) at presynaptic neurons.

Desipramine (Norpramin)

Desipramine may increase the synaptic concentration of norepinephrine in the CNS by inhibiting the reuptake by the presynaptic neuronal membrane. It may have effects in the desensitization of adenyl cyclase, downregulation of beta-adrenergic receptors, and downregulation of serotonin receptors.

Clomipramine (Anafranil)

Clomipramine affects serotonin uptake. This agent also affects norepinephrine uptake when converted into its metabolite, desmethylclomipramine.

Antidepressants, MAO Inhibitors

Class Summary

Monoamine oxidase inhibitors (MAOIs) are effective in patients with social phobia and refractory anxiety disorders, including panic disorder. Advantages of MAOIs include a low risk of dependence and less anticholinergic effect than tricyclic antidepressants (TCAs). Disadvantages include the higher number of adverse effects, including sexual difficulty, hypotension, weight gain, dry mouth, tachycardia, insomnia, drowsiness, headache, weakness, and constipation.

Phenelzine (Nardil)

Nardil is the MAOI that is most commonly used for managing panic disorder. It has demonstrated clear superiority over placebo in double-blind trials for treating specific symptoms of panic disorder. This drug is usually reserved for patients who do not tolerate or whose condition does not have a response to traditional cyclic or second-generation antidepressants.

Tranylcypromine (Parnate)

Tranylcypromine is also effective against panic disorder. It binds irreversibly to MAO, thereby reducing monoamine breakdown and enhancing synaptic availability.

Antidepressants, SNRI’s

Class Summary

Serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants inhibit serotonin reuptake receptors and, unlike the pure selective serotonin reuptake inhibitors (SSRIs), inhibit the reuptake of norepinephrine as well.

Venlafaxine (Effexor, Effexor XR)

Venlafaxine is a serotonin/norepinephrine reuptake inhibitor. It may treat depression by inhibiting neuronal serotonin and norepinephrine reuptake. In addition, it causes beta-receptor down-regulation.

Antidepressants, Others

Class Summary

Other antidepressants are those that are unique and not categorized into the classification of selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SSNIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).

Trazodone (Desyrel, Desyrel Dividose, Oleptro)

Trazodone is useful in the treatment of panic disorder and agoraphobia with panic attacks. It is an antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Trazodone also has a negligible affinity for cholinergic and histaminergic receptors.

In animals, this drug selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral changes induced by the serotonin precursor, 5-hydroxytryptophan.

Mirtazapine (Remeron, Remeron SolTab)

Mirtazapine is an alpha-2 adrenergic antagonist that increases synaptic norepinephrine and serotonin, while also blocking some postsynaptic serotonergic receptors that conceptually mediate excessive anxiety when stimulated with serotonin. This agent causes significant sedation which generally reduces its potential to aggravate initial anxiety and may cause residual morning sedation that often improves with continued therapy.

Sedating antidepressants such as mirtazapine are usually prescribed for use only at night before bed to help improve sleep, but they should include a warning for patients not to operate a motor vehicle or machinery if they are feeling sedated or directly after the dose.

Mirtazapine may also cause an increase in appetite or weight gain.


Questions & Answers


What is panic disorder?

What are the DSM-5 diagnostic criteria for panic disorder?

How is a panic disorder diagnosis confirmed?

What are the complications of panic disorder?

What are the biologic causes of panic disorder?

What are the genetic factors that contribute to panic disorder?

What is the prevalence of panic disorder in the US?

What are common comorbidities of panic disorder?

What are the demographics of panic disorder?

What is the prognosis of panic disorder?

What educational information about panic disorder should be provided to patients and their family?


What is the purpose of a medical evaluation for patients with panic disorder?

What are the manifestations of panic disorder?

How is the behavior of patients with panic disorder characterized?

What are the types of panic attacks in panic disorder?

What are the triggers of panic attacks in patients with panic disorder?

What features of the patient history should be included in the assessment of panic disorder?

What are the physical signs of panic disorder?

What is the role of a mental status exam in patients with panic disorder?

What standardized mental status screening tests are used for patients with panic disorder?


Why is it important for emergency physicians to understand panic disorders?

Which symptoms and related conditions should be considered in the diagnosis of panic disorder?

What other mental illnesses should be considered in the diagnosis of panic disorder?

Which cardiovascular diseases should be considered in the diagnosis of panic disorder?

What are the differential diagnoses for Panic Disorder?


What are the approach considerations in diagnosing panic disorder?

Which lab studies are indicated in the workup of panic disorder?

Which diagnostic measurements are relevant in the workup of panic disorder?

What is the role of imaging studies in the workup of panic disorder?


Which specialist referrals are indicated for patients with panic disorder?

When is therapy indicated for patients with panic disorder, and what are the treatment goals?

What is the role of cognitive-behavioral therapy (CBT) in the management of panic disorder?

Which medications are used in treatment of panic disorder?

When is outpatient care indicated for patients with panic disorder, and when is inpatient care warranted?

What is the management approach to panic disorder in the emergency department?


What are the subtypes of panic disorder, and how is each managed?

What is the role of drug treatment for panic disorder?

What is the role of SSRIs and TCAs in the management of panic disorder?

What are the potential adverse effects of selective serotonin reuptake inhibitors (SSRIs) in the management of panic disorder?

Which drugs other than SSRIs are used in the management of panic disorder?

What is the role of benzodiazepines in the management of panic disorder?

What are the potential adverse effects of benzodiazepines in the management of panic disorder?

How are treatment outcomes evaluated and modified when necessary in panic disorder?

What are the APA recommendations on the evaluation of treatment for panic disorder?

How is pharmacologic management of panic disorder discontinued?

How are persistent or recurrent symptoms managed in the treatment of panic disorder?

What is the potential for noncompliance in the treatment of panic disorder?

Which specialist consultations are indicated in the treatment of panic disorder?

What are the procedures for long-term monitoring of patients with panic disorder?


Which drugs are used in the treatment of panic disorder?

Which medications in the drug class Antidepressants, Others are used in the treatment of Panic Disorder?

Which medications in the drug class Antidepressants, SNRI’s are used in the treatment of Panic Disorder?

Which medications in the drug class Antidepressants, MAO Inhibitors are used in the treatment of Panic Disorder?

Which medications in the drug class Antidepressants, TCA are used in the treatment of Panic Disorder?

Which medications in the drug class Antidepressants, SSRIs are used in the treatment of Panic Disorder?

Which medications in the drug class Anxiolytics, Benzodiazepines are used in the treatment of Panic Disorder?