Panic Disorder

Panic disorder is a condition marked by recurrent and episodic panic attacks that occur abruptly and without a trigger. These episodes are time-limited and present with cardiorespiratory (palpitations, shortness of breath, choking), GI (nausea, abdominal distress), and neurologic (paresthesias, light-headedness) symptoms. Fear of dying or going crazy can occur. Patients may develop agoraphobia (fear of being in places or situations where leaving or escape is difficult). These findings lead to impaired daily functioning. Diagnosing panic disorder is challenging because panic attacks can also occur with other anxiety and mental disorders. Additionally, organic diseases can have similar symptoms. Thorough history and examination, along with a focused workup (based on patient age, risk, and comorbidities) aid in the diagnosis. Management includes both psychotherapy and medications (selective serotonin reuptake inhibitor (SSRIs) and serotonin–norepinephrine reuptake inhibitor (SNRIs)).

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Overview

Definition

Panic disorder is characterized by chronic recurrent episodes of panic attacks (not triggered) that are associated with significant worry about future attacks, maladaptive behavior, and impaired function for ≥ 1 month.

A panic attack is not a mental disorder. Rather, this disorder is a sudden, spontaneous, time-limited period (minutes to an hour) of heightened anxiety or intense fear, often with physical symptoms.

Epidemiology

  • Lifetime prevalence of panic disorder in the United States is 4.7%.
  • Women are twice likely to be affected as men. 
  • Usual onset occurs in adolescence to early 30s.
  • Close to 40% of those with panic disorder have a lifetime history of major depression.

Pathophysiology

Genetic and environmental factors play a role.

  • Genetics:
    • ↑ Rate of panic disorder in those with 1st-degree relatives with the condition
    • Higher concordance in monozygotic twins
  • Structural brain changes:
    • Involves multiple neural circuits, including the following regions: prefrontal, temporal, anterior cingulate, insula, amygdala, hippocampus, and hypothalamus
    • Alterations in these regions noted in the panic response
    • Also implicates altered GABA-benzodiazepine receptors and serotonin receptors (↑ fear generalization) 
  • Anxious temperament and neuroticism: greater reactivity to stress and poor defense against anxiety-provoking stimuli
  • History of physical or sexual abuse, smoking, and asthma also lead to increased risk of panic disorder.

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Clinical Presentation and Diagnosis

Clinical features/criteria

  • Panic attack is abrupt in onset and frequently spontaneous, but may arise from excitement, trauma, or physical exertion. 
  • Physical and mental symptoms: 
    • Palpitations, a pounding heart, or increased heart rate
    • Sweating
    • Chills or heat sensation
    • Trembling or shaking
    • Paresthesias
    • Shortness of breath 
    • Choking sensation
    • Chest pain or chest discomfort
    • Nausea or abdominal distress
    • Feeling dizzy, unsteady, light-headed, or faint
    • Derealization (feelings of unreality) or depersonalization (being detached from one’s own self)
    • Fear of losing control or of going insane/crazy
    • Fear of dying
  • Some people develop agoraphobia (fear and avoidance of situations or places where it is difficult to leave or escape, especially if panic symptoms were to occur).
  • Panic attacks followed by either/both ≥ 1 month of: 
    • Continued concern or worry about future panic attacks or their consequences (e.g., heart attack or going crazy)
    • Significant maladaptive behavioral change or inappropriate adjustment secondary to the attacks (e.g., avoidance behaviors)

Assessment

  • Complete medical, social, family, and psychiatric history with physical examination
  • Laboratory testing and further workup (e.g., ECG, Holter monitoring, pulmonary function test) based on patient’s age, risk, and medical history
  • Rule out other psychiatric disorders.
  • Rule out substance use or effects of medication(s),
  • Panic Disorder Severity Scale (PDSS):
    • Instrument uses a severity rating for different behaviors (scale: 0–4).
    • Information obtained: 
      • Attack frequency
      • Attack intensity
      • Anticipatory anxiety
      • Phobic avoidance
      • Avoidance of internal bodily sensations
      • Relationship impairment, work impairment

Management

With proper management, most patients show improvement in symptoms of panic disorder.

A choice of treatment can be CBT and/or medication, depending on patient preference, availability, and response.

Cognitive-behavioral therapy

  • Goal is to have the patient understand that panic attacks last for a short period and that they are not life-threatening. 
  • Patients are taught cognitive and somatic coping skills to recognize panic and replace catastrophic thoughts.
  • Patients are encouraged to apply these skills during exposure so that they learn to manage the symptoms.
  • Used with medications for maintenance therapy if monotherapy alone is not effective

Pharmacotherapy

  • Acute attack: 
    • Benzodiazepines (BDZs), such as alprazolam
    • Recommended for short course alongside selective serotonin reuptake inhibitors (SSRIs), such as paroxetine 
    • Must be used with caution due to side effects and potential for misuse 
  • Maintenance therapy: 
    • Antidepressants (SSRIs or serotonin–norepinephrine reuptake inhibitors (SNRIs)) are 1st-line. 
    • SSRIs include paroxetine, citalopram, and sertraline.
    • SNRIs include venlafaxine and duloxetine.
    • Need weeks or months to show their effects
    • If maintenance with SSRI fails, tricyclic antidepressants or monoamine oxidase inhibitors may be used.

Other Anxiety Disorders

Table: Comparison of anxiety disorders
ConditionMost important featuresDurationTreatment
Panic disorderRecurrent and unexpected abrupt surges (within minutes) of intense fear or discomfort≥ 1 month
  • Acute attack: BDZ
  • Maintenance: SSRI, CBT
Generalized anxiety disorderChronic multiple worries usually about issues, events, activities≥ 6 monthsCombination of antidepressants (SSRI) and CBT
Specific phobiaUnreasonable fear of a certain object or situations≥ 6 months
  • 1st-line: CBT
  • Medication has an insignificant role.
Social phobia (social anxiety disorder)Fear or avoidance of social interactions due to concerns about being embarrassed≥ 6 months
  • 1st-line: SSRI or CBT
  • Performance-only subtype: beta blockers or BDZ
AgoraphobiaFear of being in situations or places where it is difficult to leave or escape≥ 6 months1st-line: SSRI or CBT
Separation anxiety disorderFear of being separated from attachment figures≥ 1 month
  • 1st-line: CBT
  • Medications might be used if CBT alone fails.
Illness anxiety disorderAnxiety arises from concerns about having or acquiring a certain illness.≥ 6 months
  • Schedule regular follow-up visits.
  • Avoid doing unnecessary diagnostic tests.
  • Avoid referrals.
  • CBT and antidepressants if these measures fail
Substance or drug-induced anxiety disorder
  • Intoxication with cocaine or amphetamine
  • Withdrawal from alcohol or benzodiazepines
  • Medications such as β2-agonists (albuterol) or levothyroxine

Differential Diagnosis

  • Pheochromocytoma: catecholamine-secreting tumor derived from chromaffin cells. The majority of pheochromocytomas originate in the adrenal medulla, but they can also arise from sympathetic ganglia (also referred to as paragangliomas). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, pallor, tremor, and sweating. The clinical features of pheochromocytoma are very similar to those of panic disorder, but there is no severe hypertension in panic disorder. 
  • PTSD: seen after experiencing a life-threatening event. Symptoms last > 1 month and involve reexperiencing the event as flashbacks or nightmares, avoiding reminders, irritability, hyperarousal and poor memory and concentration. Panic attacks are a hallmark of PTSD but the diagnosis of PTSD must also meet other criteria, such as history of life-threatening events or presence of intrusion symptoms or negative mood changes, that are not commonly found in those with panic disorder. 
  • Generalized anxiety disorder: common mental condition defined by excessive, uncontrollable worrying that causes distress and occurs frequently for ≥ 6 months. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. If patients have symptoms of anxiety without reporting experiencing panic attacks (as defined above), they do not meet the criteria for the diagnosis of panic disorder. 
  • Withdrawal (from alcohol or benzodiazepines): patients with alcohol use disorder or anxiolytic use disorder are at increased risk of withdrawal if they discontinue their substance use abruptly. Symptoms include worsening of initial anxiety, insomnia, psychosis, and seizures. Withdrawal from alcohol and anxiolytics are distinguished from panic disorder by history, physical exam, and urine toxicology screen. 

References

  1. Dave, P. (2017). Clinical management of anxiety disorders. https://www.researchgate.net/publication/348489972_Clinical_Management_of_Anxiety_Disorders
  2. Grant, J. (2021). Overview of anxiety disorders. https://www.researchgate.net/publication/348435567_Overview_of_Anxiety_Disorders
  3. Palkar, P. (2020). Neurobiology of anxiety disorders. https://www.researchgate.net/publication/341407589_Neurobiology_of_Anxiety_Disorders
  4. Roy-Byrne, P. (2019). Panic disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis. UpToDate. Retrieved June 24, 2021, from https://www.uptodate.com/contents/panic-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis
  5. Roy-Byrne, P. (2020). Pharmacotherapy for panic disorder with or without agoraphobia in adults. UpToDate. Retrieved June 24, 2021, fromhttps://www.uptodate.com/contents/pharmacotherapy-for-panic-disorder-with-or-without-agoraphobia-in-adults
  6. Sadock, B. J., Sadock, V. A., Ruiz, P. (2014). Anxiety disorders. Chapter 9 of Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 11th ed. Philadelphia: Lippincott Williams and Wilkins, pp. 387–417.

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