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Synonyms and Keywords: Fit of terror, spasm, anxiety disorder
Panic disorder is a condition characterized by recurring panic attacks with significant behavioral change or at least a month of ongoing worry about having another attack. Panic disorder patients have a series of episodic severe anxiety, known as panic attacks. These attacks typically last 10 minutes, however, they can be of shorter duration. They may vary in intensity and symptoms over a period of time. Symptoms of panic disorder commonly present in the form of rapid heart beat, perspiration, dizziness, dyspnea, tremors, uncontrollable fear or feeling of impending doom. The panic attacks often result in 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 develop, which may eventually result in clinical depression and suicide. So, early, efficient, and affordable treatment options 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 stopped the travelers from going to the market. In Greek, agora stands for market and this led to the development of a new term 'agoraphobia'. It stands for the fear of public places or large open spaces.
- In 1621, Burton described different varieties of pathological anxiety. He related the anxiety to delirium, depersonalization, hypochondria, hyperventilation, and 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 used the term panic for the first time in psychiatry, and also explained melancholic panic.
- Sigmund Freud, in the year 1925, described anxiety neurosis. He separated it from neurasthenia and further elaborated anxiety neurosis with a particular clinical presentation.
- In 1964, Klein proposed three types of panic attacks: situational (related to agoraphobia), spontaneous, and in response to a stimulus (like height, animals, etc.). 
- In 1980, panic disorder was first described in DSM-III, based on Klein's description of panic attacks. 
- In 1987, after consistent work on DSM for the next seven years, 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 described panic attacks related to other conditions. The criteria for panic disorder was not required to be fulfilled here.
- The criteria for panic disorder remained the same in the revised version of DSM-IV (DSM-IV-TR), published in 2000.
- 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, the center for 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 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 occipital cortex GABA levels. Other studies suggest dysfunction of GABA(A) receptors in the pathophysiology of panic disorder. This is further supported by improvement in symptoms by treatment focused 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
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.  
- Women are twice as likely as men to develop panic disorder. 
- For both men and women, panic disorder has similar age of onset. 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 precipitating factor for 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 diseases.
- Anticipation is responsible for the familial aggregation of panic disorder. 
- There is an increased risk of disease in the relatives of panic disorder patients with age of onset 20 years or less. The age of onset is useful in determining the familial subtypes. 
- Various studies presented with mixed results.
- A study comparing the White, African American, Asian, and Latino groups found that the Whites 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)
- Offsprings 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 associated with at least four of these symptoms:
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. Feeling 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 of 1 month of the following:
- 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 can be successfully treated.
- Due to the disturbing symptoms that accompany the panic disorder, it can 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 of 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 such as paroxetine, escitalopram, and citalopram, are used for maintenance therapy. 
- MAOIs are usually avoided because of the life-threatening side effects such as serotonin syndrome, hypertensive crisis, and other drug interactions.
- TCAs are associated with anticholinergic side effects, so avoided in the elderly.
- Both SSRIs and TCAs are effective for the treatment but SSRIs are preferred because of a better tolerability profile.
- These are used for a short duration to control the acute phase of illness or given until the SSRIs have achieved therapeutic action.
- Long-term use is not advisable because of the high chances of developing dependence and drug-seeking behavior.
- There are multiple treatment options available such as 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 result in nearly 85% response rate. 
- Relaxation techniques produce greater reduction in the associated anxiety but are 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 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 is lesser effective than pharmacotherapy. 
- When properly used, Internet-based self-help programs with minimal therapist contact can be equally efficacious as traditional individual CBT. 
- Virtual Reality Exposure (VRE) has been found to be effective for both short and long-term management of panic disorder.
- Nardi, Antonio Egidio (2006). "Some notes on a historical perspective of panic disorder". Jornal Brasileiro de Psiquiatria. 55 (2): 154–160. doi:10.1590/S0047-20852006000200010. ISSN 0047-2085.
- Nardi, Antonio Egidio; Freire, Rafael Christophe R. (2016). "The Panic Disorder Concept: A Historical Perspective": 1–8. doi:10.1007/978-3-319-12538-1_1.
- Angst J (1998). "Panic disorder: History and epidemiology". Eur Psychiatry. 13 Suppl 2: 51s–5s. doi:10.1016/S0924-9338(98)80014-X. PMID 19698673.
- Roest, Annelieke M.; Vries, Ymkje Anna; Lim, Carmen C. W.; Wittchen, Hans‐Ulrich; Stein, Dan J.; Adamowski, Tomasz; Al‐Hamzawi, Ali; Bromet, Evelyn J.; Viana, Maria Carmen; Girolamo, Giovanni; Demyttenaere, Koen; Florescu, Silvia; Gureje, Oye; Haro, Josep Maria; Hu, Chiyi; Karam, Elie G.; Caldas‐de‐Almeida, José Miguel; Kawakami, Norito; Lépine, Jean Pierre; Levinson, Daphna; Medina‐Mora, Maria E.; Navarro‐Mateu, Fernando; O’Neill, Siobhan; Piazza, Marina; Posada‐Villa, José A.; Slade, Tim; Torres, Yolanda; Kessler, Ronald C.; Scott, Kate M.; Jonge, Peter (2019). "A comparison of
‐IV agoraphobia in the World Mental Health Surveys". Depression and Anxiety. 36 (6): 499–510. doi:10.1002/da.22885. ISSN 1091-4269. line feed character in
|title=at position 16 (help)
- Kim, Jieun E; Dager, Stephen R; Lyoo, In Kyoon (2012). "The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies". Biology of Mood & Anxiety Disorders. 2 (1): 20. doi:10.1186/2045-5380-2-20. ISSN 2045-5380.
- Massana, Guillem; Serra-Grabulosa, Josep Maria; Salgado-Pineda, Pilar; Gastó, Cristòbal; Junqué, Carme; Massana, Joan; Mercader, José Maria; Gómez, Beatriz; Tobeña, Adolf; Salamero, Manel (2003). "Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging". NeuroImage. 19 (1): 80–90. doi:10.1016/S1053-8119(03)00036-3. ISSN 1053-8119.
- Coplan, Jeremy D; Lydiard, R.Bruce (1998). "Brain circuits in panic disorder". Biological Psychiatry. 44 (12): 1264–1276. doi:10.1016/S0006-3223(98)00300-X. ISSN 0006-3223.
- "Neurobiological mechanisms of panic anxiety: biochemical and behavioral correlates of yohimbine-induced panic attacks". American Journal of Psychiatry. 144 (8): 1030–1036. 1987. doi:10.1176/ajp.144.8.1030. ISSN 0002-953X.
- Graeff, Frederico G. (2017). "Translational approach to the pathophysiology of panic disorder: Focus on serotonin and endogenous opioids". Neuroscience & Biobehavioral Reviews. 76: 48–55. doi:10.1016/j.neubiorev.2016.10.013. ISSN 0149-7634.
- Goddard, Andrew W.; Mason, Graeme F.; Almai, Ahmad; Rothman, Douglas L.; Behar, Kevin L.; Petroff, Ognen A. C.; Charney, Dennis S.; Krystal, John H. (2001). "Reductions in Occipital Cortex GABA Levels in Panic Disorder Detected With 1H-Magnetic Resonance Spectroscopy". Archives of General Psychiatry. 58 (6): 556. doi:10.1001/archpsyc.58.6.556. ISSN 0003-990X.
- Rupprecht, R.; Zwanzger, P. (2003). "Die Bedeutung von GABAA-Rezeptoren f�r Pathophysiologie und Therapie der Panikst�rung". Der Nervenarzt. 74 (7): 543–551. doi:10.1007/s00115-002-1433-x. ISSN 0028-2804. replacement character in
|title=at position 37 (help)
- Edlund, Matthew J.; McNamara, M.Eileen; Millman, Richard P. (1991). "Sleep apnea and panic attacks". Comprehensive Psychiatry. 32 (2): 130–132. doi:10.1016/0010-440X(91)90004-V. ISSN 0010-440X.
- Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
- "Facts about Panic Disorder". National Institute of Mental Health. Retrieved 2006-09-30.
- Barzega, Giulio; Maina, Giuseppe; Venturello, Sara; Bogetto, Filippo (2001). "Gender-related differences in the onset of panic disorder". Acta Psychiatrica Scandinavica. 103 (3): 189–195. doi:10.1034/j.1600-0447.2001.00194.x. ISSN 0001-690X.
- Battaglia, Marco; Bertella, Silvana; Bajo, Sonia; Binaghi, Flora; Bellodi, Laura (1998). "Anticipation of Age at Onset in Panic Disorder". American Journal of Psychiatry. 155 (5): 590–595. doi:10.1176/ajp.155.5.590. ISSN 0002-953X.
- Goldstein, Rise B. (1997). "Familial Aggregation and Phenomenology of 'Early'-Onset (at or Before Age 20 Years)". Archives of General Psychiatry. 54 (3): 271. doi:10.1001/archpsyc.1997.01830150097014. ISSN 0003-990X.
- Asnaani, Anu; Gutner, Cassidy A.; Hinton, Devon E.; Hofmann, Stefan G. (2009). "Panic Disorder, Panic Attacks and Panic Attack Symptoms across Race-Ethnic Groups: Results of the Collaborative Psychiatric Epidemiology Studies". CNS Neuroscience & Therapeutics. 15 (3): 249–254. doi:10.1111/j.1755-5949.2009.00092.x. ISSN 1755-5930.
- Roy-Byrne, Peter P; Craske, Michelle G; Stein, Murray B (2006). "Panic disorder". The Lancet. 368 (9540): 1023–1032. doi:10.1016/S0140-6736(06)69418-X. ISSN 0140-6736.
- Angst J, Vollrath M (1991). "The natural history of anxiety disorders". Acta Psychiatr Scand. 84 (5): 446–52. PMID 1776498.
- . doi:10.1007/BF00452785. Missing or empty
- Liebowitz MR (1997). "Panic disorder as a chronic illness". J Clin Psychiatry. 58 Suppl 13: 5–8. PMID 9402913.
- Ersoy, Mehmet Akif; Selek, Salih; Celik, Hakim; Erel, Ozcan; Kaya, Mehmet Cemal; Savas, Haluk A.; Herken, Hasan (2009). "Role of Oxidative and Antioxidative Parameters in Etiopathogenesis and Prognosis of Panic Disorder". International Journal of Neuroscience. 118 (7): 1025–1037. doi:10.1080/00207450701769026. ISSN 0020-7454.
- Keijsers, Ger P.J.; Hoogduin, Cees A.L.; Schaap, Cas P.D.R. (1994). "Prognostic factors in the behavioral treatment of panic disorder with and without agoraphobia". Behavior Therapy. 25 (4): 689–708. doi:10.1016/S0005-7894(05)80204-7. ISSN 0005-7894.
- Coryell, William; Noyes, Russell; Reich, James (1991). "The prognostic significance of HPA-axis disturbance in panic disorder: A three-year follow-up". Biological Psychiatry. 29 (2): 96–102. doi:10.1016/0006-3223(91)90038-N. ISSN 0006-3223.
- Stahl, Stephen M.; Gergel, Ivan; Li, Dayong (2003). "Escitalopram in the Treatment of Panic Disorder". The Journal of Clinical Psychiatry. 64 (11): 1322–1327. doi:10.4088/JCP.v64n1107. ISSN 0160-6689.
- Ballenger, James C.; Wheadon, David E.; Steiner, Martin; Bushnell, William; Gergel, Ivan P. (1998). "Double-Blind, Fixed-Dose, Placebo-Controlled Study of Paroxetine in the Treatment of Panic Disorder". American Journal of Psychiatry. 155 (1): 36–42. doi:10.1176/ajp.155.1.36. ISSN 0002-953X.
- Bakker, A.; Van Balkom, A. J. L. M.; Spinhoven, P. (2002). "SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis". Acta Psychiatrica Scandinavica. 106 (3): 163–167. doi:10.1034/j.1600-0447.2002.02255.x. ISSN 0001-690X.
- Barlow, David H.; Craske, Michelle G.; Cerny, Jerome A.; Klosko, Janet S. (1989). "Behavioral treatment of panic disorder". Behavior Therapy. 20 (2): 261–282. doi:10.1016/S0005-7894(89)80073-5. ISSN 0005-7894.
- Telch, Michael J.; Lucas, John A.; Schmidt, Norman B.; Hanna, Henry H.; Jaimez, T.LaNae; Lucas, Richard A. (1993). "Group cognitive-behavioral treatment of panic disorder". Behaviour Research and Therapy. 31 (3): 279–287. doi:10.1016/0005-7967(93)90026-Q. ISSN 0005-7967.
- Broocks, Andreas; Bandelow, Borwin; Pekrun, Gunda; George, Annette; Meyer, Tim; Bartmann, Uwe; Hillmer-Vogel, Ursula; Rüther, Eckart (1998). "Comparison of Aerobic Exercise, Clomipramine, and Placebo in the Treatment of Panic Disorder". American Journal of Psychiatry. 155 (5): 603–609. doi:10.1176/ajp.155.5.603. ISSN 0002-953X.
- Carlbring, Per; Nilsson-Ihrfelt, Elisabeth; Waara, Johan; Kollenstam, Cecilia; Buhrman, Monica; Kaldo, Viktor; Söderberg, Marie; Ekselius, Lisa; Andersson, Gerhard (2005). "Treatment of panic disorder: live therapy vs. self-help via the Internet". Behaviour Research and Therapy. 43 (10): 1321–1333. doi:10.1016/j.brat.2004.10.002. ISSN 0005-7967.
- Botella, C.; García-Palacios, A.; Villa, H.; Baños, R. M.; Quero, S.; Alcañiz, M.; Riva, G. (2007). "Virtual reality exposure in the treatment of panic disorder and agoraphobia: A controlled study". Clinical Psychology & Psychotherapy. 14 (3): 164–175. doi:10.1002/cpp.524. ISSN 1063-3995.