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 Agoraphobia Agoraphobia is fear or anxiety in a situation that would be difficult to leave or to obtain help in the event that one develops panic-like symptoms. Situations include being in public or open spaces, lines, crowds, or public transport. 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 Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. 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 Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of 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 Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. 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 Sexual Abuse Sexual abuse and assault are major public health problems that affect many people from all walks of life, including people of all ages and genders, but it is more prevalent in women and girls, with reports of up to 1 in 3 experiencing sexual assault at some time in their life. Sexual Abuse, smoking, and asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. 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 Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. 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 Agoraphobia Agoraphobia is fear or anxiety in a situation that would be difficult to leave or to obtain help in the event that one develops panic-like symptoms. Situations include being in public or open spaces, lines, crowds, or public transport. 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 ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (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 Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines (BDZs), such as alprazolam
    • Recommended for short course alongside selective serotonin reuptake inhibitors Serotonin Reuptake Inhibitors Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressant Medications (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 Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants or monoamine oxidase inhibitors Monoamine oxidase inhibitors Monoamine oxidase inhibitors are a class of antidepressants that inhibit the activity of monoamine oxidase (MAO), thereby increasing the amount of monoamine neurotransmitters (particularly serotonin, norepinephrine, and dopamine). The increase of these neurotransmitters can help in alleviating the symptoms of depression. Monoamine Oxidase Inhibitors may be used.

Other Anxiety Disorders

Table: Comparison of anxiety disorders
Condition Most important features Duration Treatment
Panic disorder Recurrent and unexpected abrupt surges (within minutes) of intense fear or discomfort ≥ 1 month
  • Acute attack: BDZ
  • Maintenance: SSRI, CBT
Generalized anxiety disorder Generalized anxiety disorder Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. Generalized Anxiety Disorder Chronic multiple worries usually about issues, events, activities ≥ 6 months Combination of antidepressants (SSRI) and CBT
Specific phobia Unreasonable fear of a certain object or situations ≥ 6 months
  • 1st-line: CBT
  • Medication has an insignificant role.
Social phobia ( social anxiety disorder Social anxiety disorder Social anxiety disorder, or social phobia, is a psychiatric illness marked by fear and avoidance of social interactions due to concerns about embarrassment. The disorder usually occurs in more than one social situation for more than 6 months and leads to a significant decline in function. 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
Agoraphobia Fear of being in situations or places where it is difficult to leave or escape ≥ 6 months 1st-line: SSRI or CBT
Separation anxiety disorder Fear of being separated from attachment figures ≥ 1 month
  • 1st-line: CBT
  • Medications might be used if CBT alone fails.
Illness anxiety disorder Illness Anxiety Disorder Illness anxiety disorder, formerly known as hypochondriasis, is a chronic condition characterized by a prolonged and exaggerated concern about one's health and possible illness. Patients fear or are convinced that they have a disease and interpret minor or normal bodily symptoms as signs of a serious medical condition. Illness Anxiety Disorder Anxiety arises from concerns about having or acquiring a certain illness. ≥ 6 months
  • Schedule regular follow-up visits.
  • Avoid doing unnecessary diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of 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 Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. 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 Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. 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 Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension in panic disorder. 
  • PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress 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 PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD) but the diagnosis of PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (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 Generalized anxiety disorder Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. 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 Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of 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 Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. 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 Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, psychosis, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. 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 Agoraphobia Agoraphobia is fear or anxiety in a situation that would be difficult to leave or to obtain help in the event that one develops panic-like symptoms. Situations include being in public or open spaces, lines, crowds, or public transport. 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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