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Panic disorder is a condition characterized by recurring panic attacks in combination with significant behavioral change or at least a month of ongoing worry about the implications of having another attack. Panic disorder patients have a series of episodes of severe anxiety, known as panic attacks. These attacks typically last 10 minutes, however, they can be short-lived for around 1-5 minutes. They may vary in intensity and symptoms over a period of time. Symptoms of panic disorder commonly presents in the form of rapid heart beat, perspiration, dizziness, dyspnea, tremors, uncontrollable fear or feeling of impending doom. The panic attacks often result in negative social experiences in the form of embarrassment and social stigma, ultimately resulting in social isolation. Therefore, most of the individuals with panic disorder also develop agoraphobia. If not treated, somatic symptoms like insomnia and/or anorexia can occur, which may eventually result in clinical depression and suicide. So, early, efficient, and affordable treatment options like internet self-help groups should be encouraged.
- Panic disorder has a long history, dating back to folklores.
- Greek Mythology includes one of the examples. The term 'Panic' originated from the Greek god, Pan who was responsible for anxiety.
- In Greek myths, 'Pan' was a man with horns and legs of a goat. His mere appearance was so frightening that it developed irrational fear in people, without any apparent reason. This came to be known as panic attacks or terrors. 
- Fear of meeting Pan once more made travelers stop going to the market. In Greek, agora stands for market and this led to the development of the term 'agoraphobia'. It stands for the fear of public places or large open spaces.
- In 1621, Burton elaborated different varieties of pathological anxiety. He related the anxiety to delirium, depersonalization, hypochondria, hyperventilation, and a variety of phobias.
- In 1812, Benjamin Rush (father of American psychiatry), described the relation between somatic causes and phobias in his book. He established an association between depression and hypochondriasis. 
- In 1879, Henry Maudsley elaborated a melancholic panic, and also used the term panic for the first time in psychiatry.
- Sigmund Freud, in the year 1925, described the condition of anxiety neurosis. He separated anxiety neurosis from neurasthenia and further explained it with a particular clinical presentation.
- In 1964, Klein elaborated the three types of panic attacks: situational (related to agoraphobia), spontaneous, and in response to a stimulus (like height, animals, etc.). 
- In 1980, due to Klein's description of panic attacks,for the first time panic disorder was described in DSM-III. 
- After consistent work on DSM for the next seven years, in 1987, DSM-III-R described agoraphobia as a consequence of panic disorder. So, agoraphobia was divided into 'panic disorder with and without agoraphobia'.
- In 1992, DSM-IV also defined panic attacks to occur in relation to other conditions. It was not required to fulfill all the criteria for panic disorder.
- A revised version of DSM-IV was published in 2000, entitled DSM-IV-TR, in which the criteria for panic disorder remained the same.
- DSM-5 has unlinked panic disorder and agoraphobia. 
- The tenth edition of International Classification of Diseases (ICD-10) describes agoraphobia as a distinct condition that may not occur with panic attacks.
- Multiple factors are associated with the pathophysiology of panic disorder.
- Imbalance of neurobiological, neuroanatomic, and neurochemical factors lead to the production of this condition.
- Pathogenesis of Panic Disorder is related to the amygdala, which is the hub of emotions like fear processing. MRI studies have further substantiated this finding by showing lesser left and right-sided amygdalar volumes in panic disorder patients as compared to controls. 
- There is dysregulation of the prefrontal cortex as well as the subcortical components.
- The patients with panic disorder are also hypothesized to have more noradrenergic neuronal activity than controls. 
- Another neurochemical theory proposes that these patients have deficient serotonergic inhibition of neurons in the dorsal periaqueductal gray matter of the midbrain and the rostral ventrolateral medulla. 
- The endogenous opioids buffer the panic attacks in normal subjects and their deficit results in the development of the panic disorder. 
- Panic disorder patients have also been found to have lower total occipital cortex GABA levels. Evidence by other studies suggests dysfunction of GABA(A) receptors in the pathophysiology of panic disorder. This is further illustrated by improvement in symptoms by treatment focussing on GABA binding site of the GABA(A) and benzodiazepine receptor complex. 
- Anxiety disorder due to other medical condition
- Vestibular abnormalities
- Seizure disorders
- Sleep apnea
- Cardiopulmonary conditions
- Other mental disorders with panic attacks
- Medication-induced anxiety disorder
Epidemiology and Demographics
- The prevalence of the panic disorder is 2,000-3,000 / 100,000 (2%-3%) of the overall population.
- 2.7-7.1% of the general population suffers from a lifetime prevalence of panic disorder, means having repeated panic attacks.  
- Women are twice as likely as men to develop the panic disorder. 
- Similar age at onset of Panic Disorder is observed for men and women. Preceding premorbidity was found to be different for men and women.
- Men had higher rates of body dysmorphic disorder, cyclothymia, and depersonalization preceding panic disorder. Whereas, women had higher rates of bulimia nervosa. Life stressors played a significant role in precipitating Panic Disorder in women.
- Anticipation is characterized by the decrease in age at onset and/or the increase in severity of a disorder in successive generations. It helps in exploring the genetic basis of some familial illness.
- Anticipation is observed in panic disorder and the is responsible for the familial aggregation of this condition. 
- There is an increased risk of panic disorder in relatives of individuals with panic disorder onset at or before the age of 20 years. The age of onset is useful in determining the familial subtypes of panic disorder.
- Various studies presented with mixed results.
- A study comparing the White, African American, Asian, and Latino groups found that the White group had higher rates of panic disorder, as compared to the African American, Latino, and Asian groups.
- Childhood sexual and physical abuse
- Genetic predisposition
- History of "fearful spells"
- Identifiable stressors
- Interpersonal stressors
- Stressors related to physical well-being
- Negative experiences with illicit or prescription drugs
- Death in the family
- Negative affect (neuroticism)
- Offspring of parents with anxiety, depression, or bipolar disorders
- Separation anxiety in childhood
Natural History, Complications, and Prognosis
- Anxiousness in people with panic disorder begins in childhood due to traumatic life events or distressing family conditions.
- Family history and genetics play a very important role in the development of panic disorder.
- Poor prognostic factors are:
DSM-5 Diagnostic Criteria for Panic Disorder
- A. Recurrent unexpected panic attacks. A panic attack is an abrupt surge of intense fear or discomfort that reaches a peak within minutes, and during which time four (or more) of these symptoms occur;
Note:The abrupt surge can occur from a calm state or an anxious state.
- 1. Palpitations
- 2. Sweating
- 3. Trembling
- 4. Shortness of breath
- 5. Feelings of choking
- 6. Chest pain or discomfort
- 7. Nausea or abdominal distress
- 8. Feeling dizzy, or unsteady
- 9. Chills or sensation of heat
- 10. Paresthesias (numbness or tingling sensations)
- 11. Derealization (feelings of unreality) or depersonalization (being detached from oneself)
- 12. Fear of losing control
- 13. Fear of dying
- B. At least one of the attacks has been followed by a minimum 1 month (or more) duration of one or both:
- 1. Persistent worries about having another panic attack or the consequences (like losing control).
- 2. A major maladaptive behavioral change in relation to the attacks (behaviors to avoid having panic attacks)
- C. The disturbance is not due to the effects of a substance or another medical condition
- D. The disturbance is not better explained by another mental disorder or due to separation from attachment figures
- Panic Disorder is a potentially disabling condition, but it can be successfully treated.
- Due to the disturbing symptoms that accompany the panic disorder, it may be mistaken for a life-threatening physical illness.
- Thorough investigation to rule out the suspected medical condition and early initiation of treatment should be the ultimate goal for managing the panic disorder.
- Panic disorder can be treated by medications, psychotherapy, or both.
- A skilled treating team of psychiatrists, psychologists, and social workers is required for this purpose.
- SSRIs like paroxetine, escitalopram, citalopram, etc. are used for maintenance therapy. 
- MAOIs are usually avoided because of the associated life-threatening side effects like serotonin syndrome, hypertensive crisis, and other drug interactions.
- TCAs like Imipramine is associated with anticholinergic side effects, so avoided in the elderly.
- Both SSRIs are TCAs are effective in treatment but SSRIs are better tolerated and so they are preferred.
- These are used for a short duration to control the acute phase of illness or given until the SSRIs have achieved the therapeutic action.
- Long-term use is not advised because of the chances of developing dependence and drug-seeking behavior.
- There are multiple treatment options available like- Exposure to somatic cues, cognitive behavior therapy (CBT), and relaxation therapy for panic disorder. When combined, these management options provide the best results.
- Exposure to somatic cues and CBT, when combined resulted in about an 85% response rate. 
- Relaxation technique resulted in greater reductions in the anxiety associated with panic attacks but was found to be related to higher drop-out rates. 
- CBT can also be administered in the form of group therapy. It is found to be equally effective as compared to pharmacotherapy in some studies.
- CBT comprises of: 
- Education and corrective information
- Cognitive therapy
- Training in diaphragmatic breathing
- Interoceptive exposure
Other treatment modalities
- Regular aerobic exercise alone has been associated with clinical improvement in patients with panic disorder but it is lesser effective than pharmacotherapy. 
- Internet-based self-help programs plus minimal therapist contact can be equally efficacious as traditional individual CBT. 
- Both for short and long-term treatment of panic disorder with or without agoraphobia, Virtual Reality Exposure (VRE) has been found to be effective.
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