Panic Disorder

Primer

Panic disorder is a condition where there are recurrent unexpected panic attacks, in the absence of triggers. It is marked by persistent concern about additional panic attacks and/or maladaptive change in behaviour related to the attacks.

Epidemiology
  • The lifetime prevalence of panic disorder is between 2-3% in the United States
    • Rates are much lower in Asian, African, and Latin American countries; it is similarly lower in Latinos, African Americans, Caribbean blacks, and Asian Americans.[1]
  • It affects 2 females for every 1 male.[2]
  • The rates of panic disorder gradually increase in adolescence and peak during adulthood.[3]
    • The median age of onset is between 20 to 24 years in the United States.[4]
Prognosis
  • Youth with panic attacks may go on to develop mood disorders such as bipolar disorder and major depressive disorder, other anxiety disorders, eating disorder, psychotic disorders, and personality disorders.[5][6]
  • Panic disorder can have a negative impact on physical and psychological function, in addition to stress on the individual's interpersonal functioning (especially with their family members).[7]
  • Typically, panic disorder has a chronic waxing and waning course over the individual's lifetime.[8]
  • Individuals with panic disorder are at a higher risk for suicide.[9]
Note: The prevalence of panic attacks (not disorder) is 11.2% in adults, and can occur in the context of anxiety disorders, other mental disorders, and medical conditions. Panic attacks in and of themselves are not pathological, and do not require treatment.
Comorbidity
  • Individuals with panic disorder have a significantly higher risk of being diagnosed with another anxiety disorder, mood disorder, impulse control disorder, or substance use disorder.
    • Major depressive disorder is the most common, and occurs in an estimated 30 to 40% of individuals.[10]
    • Panic disorder also commonly cooccurs with agoraphobia.[11]
Risk Factors
  • Adverse childhood experiences can increase the risk for panic disorder.[12]
  • Smoking is a risk factor for panic attacks and panic disorder.
  • Most individuals with panic attacks are also able to identify a stressor in the months prior to their panic attack.[13]
  • Panic disorder is more prevalent in patients with medical conditions, including thyroid disease, cancer, chronic pain, cardiac disease, irritable bowel syndrome, migraine, as well as allergic and respiratory diseases compared with the general population.
  • Agents such as sodium lactate, yohimbine, caffeine, isoproterenol, carbon dioxide, and cholecystokinin, can provide panic attacks in individuals with panic disorder more so than in healthy controls (but this is not a diagnostic marker).[14]
Cultural
  • Panic attacks can have various cultural interpretations and is linked to various cultural syndromes.[15] Having an understanding of the cultural concepts of disease and mental disorders is important when assessing panic attack symptoms in a cultural context.[16]
    • In Hispanic individuals, ataque de nervios (“attack of nerves”) is a cultural syndrome used frequently to describe symptoms of intense emotional upset including acute anxiety, anger, or grief, screaming and shouting uncontrollably, attacks of crying, trembling, feeling of heat in the chest rising into the head, and verbal and physical aggression.[17] Some individuals may even report dissociative episodes.
    • In Cambodians, “Khyâl attacks” (khyâl cap) or “wind attacks” include palpitations, shortness of breath, dizziness, and cold extremities. Individuals also have other symptoms of anxiety and autonomic arousal such as neck soreness and tinnitus.[18]

Diagnostic Criteria

Criterion A

Recurrent unexpected panic attacks. A panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time at least 4 of the following symptoms occur (Note: The abrupt surge can occur from a calm state or an anxious state):

  1. Sweating
  2. Trembling or shaking
  3. Unsteady, dizziness, light-headed, or faint
  4. Derealization (feelings of unreality) or depersonalization (being detached from one self)
  5. Excessive/accelerated heart rate, palpitations, or pounding heart
  6. Nausea or abdominal distress
  7. Tingling, numbness, parathesesias
  8. Shortness of breath
  9. Fear of losing control or “going crazy”
  10. Fear of dying
  11. Choking feelings
  12. Chest pain or discomfort
  13. Chills or heat sensations
Note: Culture-specific symptoms (e.g. - tinnitus, neck soreness, headache, uncontrollable screaming or crying) may be seen. Such symptoms should not count as one of the four required symptoms.

Panic Attack Definition

  • A panic attack is a single, discrete episode of intense fear and discomfort.
  • A panic attack can be expected or unexpected, but in order to diagnose panic disorder, there must be at least one unexpected panic attack!
  • A panic attack must peak abruptly (rapid onset of under 10 minutes), and must be accompanied by a cluster of physical symptoms.
  • A typical panic attack is relatively short and lasts no more than 15 minutes.

Mnemonic

The mnemonic STUDENTS FEAR the 3 C's can be used to remember the panic disorder criteria:

  • S - Sweating
  • T - Trembling
  • U - Unsteadiness, dizziness
  • D - Depersonalization, derealization
  • E - Excessive heart rate, palpitations
  • N - Nausea
  • T - Tingling
  • S - Shortness of breath
  • FEAR of dying
  • FEAR of losing control
  • FEAR of going crazy
  • C - Chest pain
  • C - Chills
  • C - Choking
Criterion B

At least 1 of the attacks has been followed by at least 1 month of at least 1 of the following:

  1. Persistent concern or worry about additional panic attacks or their consequences (e.g. - losing control, having a heart attack, “going crazy”).
  2. A significant maladaptive change in behavior-related to the attacks (e.g. - behaviors designed to avoid having panic attacks, such as avoidance of exercise or unfamiliar situations).
Criterion C

The disturbance is not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication) or another medical condition (e.g. - hyperthyroidism, cardiopulmonary disorders).

Criterion D

The disturbance is not better explained by another mental disorder:

Signs and Symptoms

  • 50% of individuals with panic disorder have expected panic attacks in addition to unexpected panic attacks.
    • Thus, having expected panic attacks does not rule out the diagnosis of panic disorder. However, at least one unexpected full symptom panic attack is required for the diagnosis of panic disorder (as per Criterion A).[19]
  • The frequency and severity of panic attacks can differ greatly between people
    • Moderate frequency can be one per week for several months, or
    • Individuals may have “bursts” of frequent daily panic attacks and then weeks or months without any attacks.[20]
  • Individuals also may have maladaptive behaviours to minimize or avoid panic attacks or the consequences of the panic attacks (e.g. - avoiding physical exertion, restricting usual activities, avoiding agoraphobia-type situations, reorganizing routines to ensure that help is available in the event of a panic attack, severe restrictions on food intake or medications for fear it may trigger attacks).
  • Between 1/3 to 1/4 of individuals may also have nocturnal panic attacks that wake them from sleep.[21]

Asking 'Do you experience panic attacks?' is too vague!

A 'panic attack' means different things to different people, and they may not actually be experiencing panic attacks. It is more important to explore whether a cluster of physical symptoms occurs and the chronology of the symptoms. It is also helpful to identify if there are specific triggers that lead to symptoms.

A true panic attack occurs only during a discrete period of time, must peak abruptly, and is accompanied by physical symptoms. Chronic anxiety on the other hand fluctuates over a period of hours to days.

Screening and Rating Scales

Panic Disorder Scales

Name Rater Description Download
Panic Disorder Severity Scale (PDSS) Clinician The PDSS is a 7 question scale to grade panic disorder severity. Download

Pathophysiology

  • Multiple genes are thought to confer a risk for the development of panic disorder.[22]
  • Current neuroscience models of panic disorder suggest that the amygdala has a role in the development of panic disorder.[23]
  • Panic attacks are also thought to be related to hypersensitive medullary carbon dioxide detectors, resulting in hypocapnia and respiratory changes.[24]

Learning Theory

  • The learning theory of panic disorder posits that classical conditioning plays a role in the development of panic disorder.
  • During a panic attack, if an individual immediately left a situation where the panic attack occurred (e.g. - at a party), the panic symptoms subside, and the behaviour of escape is “rewarded” by the reduction in panic symptoms (this is called negative reinforcement). The removal (“negative”) of unpleasant panic symptoms leads to an increase in that behaviour (“reinforcement”), hence the term negative reinforcement.[25]

Differential Diagnosis

  • Other specified anxiety disorder or unspecified anxiety disorder
    • Panic disorder should not be diagnosed if full-symptom (i.e. - unexpected) panic attacks have never been experienced. In the case of only limited-symptom unexpected panic attacks, the diagnosis of “other specified anxiety disorder or unspecified anxiety disorder diagnosis” should be considered.
  • Anxiety disorder due to another medical condition
    • Panic disorder should not be diagnosed if the panic attacks are thought to be a direct physiological result of another medical condition.
    • Features such as onset after age 45 years or the presence of atypical symptoms during a panic attack (e.g. - vertigo, loss of consciousness, loss of bladder or bowel control, slurred speech, amnesia) suggest the possibility that an other medical condition or a substance may be causing the panic attack symptoms.
    • Examples of medical conditions that can cause panic attacks include hyperthyroidism, hyperparathyroidism, pheochromocytoma, vestibular dysfunctions, seizure disorders, and cardiopulmonary conditions (e.g. - arrhythmias, atrial fibrillation, flutter, palpitations, dyspnea, syncope, supraventricular tachycardia, asthma, and chronic obstructive pulmonary disease [COPD])
  • Acute coronary syndrome or myocardial infarction (MI)[26]
    • This is especially important for women, who commonly present with atypical features of MI compared with men, and their symptoms may be dismissed as a “panic attack.”
  • Endocrinopathies
    • Cushing disease, diabetes mellitus (check for hypoglycemia), thyroid disease, parathyroid disease (hyperparathyroidism, pseudo-hyperparathyroidism), pancreatic tumours, and pituitary disease may cause symptoms similar to panic attacks.
    • Pheochromocytomas should be considered on the differential in rare cases, especially if the patient is not responding to conventional treatments.[27][28]
      • The classic triad of pheochromocytoma symptoms includes headache, excessive sweating, and palpitations. Around 15%-20% of patients with a pheochromocytoma patients may be normotensive.
  • Substance/medication-induced anxiety disorder
    • Panic disorder should not be diagnosed if the panic attacks are judged to be a direct physiological consequence of a substance. Intoxication with central nervous system stimulants (e.g. - cocaine, amphetamines, caffeine) or cannabis and withdrawal from central nervous system depressants (e.g. - alcohol, barbiturates) can precipitate a panic attack. However, if panic attacks continue to occur out side of the context of substance use (e.g. - long after the effects of intoxication or withdrawal have ended), a diagnosis of panic disorder should be considered. Since panic disorder may precede substance use in some individuals and may be associated with increased substance use (i.e. - self medication), a detailed history should be taken to see if the individual had panic attacks prior to excessive substance use. If this is the case, a diagnosis of panic disorder should be considered in addition to a diagnosis of substance use disorder.
  • Other mental disorders with panic attacks as an associated feature (e.g. - other anxiety disorders and psychotic disorders)
    • Panic attacks that occur as a symptom of other anxiety disorders are expected. For example, panic attacks can be triggered by:
    • In each of these above cases, the individual would not meet criteria for panic disorder. Remember always that panic disorder is characterized by recurrent unexpected panic attacks, and the unexpected nature of the panic attacks is a defining feature of the disorder. If the panic attacks typically only occur in response to specific triggers, then only the relevant anxiety disorder is assigned. However, if the individual experiences unexpected panic attacks as well and then begins to show persistent concern and worry or begins making behavioural change because of the attacks, then an additional diagnosis of panic disorder may be considered.

Investigations

  • Depending on the initial presenting symptoms (e.g. - dizziness, tachycardia), potential investigations can include: CBC, fasting glucose, fasting lipid profiles, electrolytes, liver enzymes, serum bilirubin, serum creatinine, urinalysis, urine toxicology for substance use, thyroid stimulating hormone (TSH).[29]
    • Generally speaking, a TSH level should be always be ordered
  • Consider an electrocardiogram (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.
  • If considering a work up for pheochromocytoma, the following investigations are recommended: plasma metanephrines (95% sensitivity), 24-hour urinary metanephrines (99% sensitivity), abdominal MRI (100% sensitivity, pheochromocytomas demonstrate a distinctive appearance), scintigraphy, and/or abdominal CT.[30]
  • If panic attacks are acute and associated with cardiac symptoms and persistent vital sign changes, consider a pulmonary embolism work up and order D-dimer.

Physical Exam

  • Cardiac, respiratory, and abdominal exam should be performed according to the clinical presentation.

Treatment

  • During the acute phase (i.e. - first 4 to 12 weeks), combination cognitive behavioural therapy with exposure and medication should be offered (as medication may be especially helpful in cases where symptoms are too distressing for patients to be able to do exposure therapy).[31][32]
  • During the follow up and recovery phase, combination therapy is superior to medications alone.[33]
    • Similarly, CBT alone is as effective as doing combination therapy during this phase.
    • At the three year follow up point in some studies, the benefits of CBT are still maintained, whereas they are not maintained in medication-only treatment.
  • Additionally, there is also evidence to suggest that adding benzodiazepines to psychotherapy may be worse than doing therapy alone.[34]

Psychotherapy

Psychotherapy Tip

It is often helpful to explain to patients that having panic disorder is like having a car with an oversensitive alarm system: every car has an alarm system that activates when a window is smashed, but sometimes the alarm system can be hypersensitive, and even a small bump or breeze can activate it.
  • Cognitive behavioural therapy has been extensively studied in panic disorder and is very efficacious in the treatment for panic disorder agoraphobia, and is preferred by patients.[35][36]
    • The addition of exposure makes the therapy even more effective.[37]
  • Psychodynamic therapy has also been used in the treatment of panic disorder.[38][39]
  • Since the evidence is so strong for psychotherapy, it should be offered as a first line treatment alone, or in combination with medications.[40]

Pharmacotherapy

Pharmacotherapy for Panic Disorder (and Agoraphobia)

Katzman, M. A. et al. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
1st line Citalopram, escitalopram,[41] fluoxetine, fluvoxamine, paroxetine, paroxetine CR, sertraline, venlafaxine XR
2nd line Alprazolam, clomipramine, clonazepam, diazepam, imipramine,[42] lorazepam, mirtazapine, reboxetine
3rd line Bupropion SR, divalproex, duloxetine, gabapentin, levetiracetam, milnacipran, moclobemide, olanzapine, phenelzine, quetiapine, risperidone, tranylcypromine
Adjunctive therapy Second-line: alprazolam ODT, clonazepam
Third-line: aripiprazole, divalproex, olanzapine, pindolol, risperidone
Not recommended Buspirone, propranolol, tiagabine, trazodone
CR = controlled release; ODT = orally disintegrating tablets; SR = sustained release; XR = extended release

Guidelines

Panic Disorder Guidelines

Guideline Location Year PDF Website
Canadian Clinical Practice Guidelines for the Management of Anxiety, Posttraumatic Stress and Obsessive-Compulsive Disorders Canada 2014 - Link
National Institute for Health and Care Excellence (NICE) UK 2011, 2019 - Link
American Psychiatric Association (APA) USA 2009 - • Guideline (2009)
• Quick Reference Guide
Royal Australian and New Zealand
College of Psychiatrists (RANZCP) 		AUS, NZ 2018 - Link

Resources

For Patients
For Providers
Articles
Research

References

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2) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
3) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
4) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
5) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
6) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
7) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
8) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
9) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
10) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
11) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
12) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
13) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
14) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
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16) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
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27) Alguire, C., Chbat, J., Forest, I., Godbout, A., & Bourdeau, I. (2018). Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment. Endocrinology, diabetes & metabolism case reports, 2018.
28) Muroya, Y., Kumagai, N., Shimodaira, M., Tsuzawa, K., Sorimachi, E., Arioka, H., & Honda, K. (2013, April). A case of pheochromocytoma that recognized as panic disorder before its exact diagnosis. In 15th European Congress of Endocrinology (Vol. 32). BioScientifica.
29) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
30) Clinical Advisor: An incidental finding, twice removed in an anxious patient
31) Bohni, M. K., Spindler, H., Arendt, M., Hougaard, E., & Rosenberg, N. K. (2009). A randomized study of massed three‐week cognitive behavioural therapy schedule for panic disorder. Acta Psychiatrica Scandinavica, 120(3), 187-195.
32) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
33) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
34) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
35) Roshanaei‐Moghaddam, B., Pauly, M. C., Atkins, D. C., Baldwin, S. A., Stein, M. B., & Roy‐Byrne, P. (2011). Relative effects of CBT and pharmacotherapy in depression versus anxiety: is medication somewhat better for depression, and CBT somewhat better for anxiety?. Depression and anxiety, 28(7), 560-567.
36) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
37) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
38) Busch, F. N., Milrod, B. L., & Singer, M. B. (1999). Theory and technique in psychodynamic treatment of panic disorder. The Journal of psychotherapy practice and research, 8(3), 234.
39) Beutel, M. E., Scheurich, V., Knebel, A., Michal, M., Wiltink, J., Graf-Morgenstern, M., ... & Subic-Wrana, C. (2013). Implementing panic-focused psychodynamic psychotherapy into clinical practice. The Canadian Journal of Psychiatry, 58(6), 326-334.
40) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.
41) Townsend, M. H., & Conrad, E. J. (2007). The therapeutic potential of escitalopram in the treatment of panic disorder. Neuropsychiatric disease and treatment, 3(6), 835.
42) Barlow, D. H., Gorman, J. M., Shear, M. K., & Woods, S. W. (2000). Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. Jama, 283(19), 2529-2536.