Panic disorder

Panic disorder

A person calmed down after having a panic attack
Classification and external resources
ICD-10 F41.0
ICD-9 300.01, 300.21
OMIM 167870
DiseasesDB 30913
MedlinePlus 000924
eMedicine article/287913
Patient UK Panic disorder
MeSH D016584

Panic disorder is an anxiety disorder characterized by recurring panic attacks, causing a series of intense episodes of extreme anxiety during panic attacks. It may also include significant behavioral changes lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks (DSM-IVR).

Panic disorder is not the same as agoraphobia (fear of public places), although many afflicted with panic disorder also suffer from agoraphobia. Panic attacks cannot be predicted, therefore an individual may become stressed, anxious or worried wondering when the next panic attack will occur.[1] Panic disorder may be differentiated as a medical condition, or chemical imbalance. The DSM-IV-TR describes panic disorder and anxiety differently. Whereas anxiety is preceded by chronic stressors which build to reactions of moderate intensity that can last for days, weeks or months, panic attacks are acute events triggered by a sudden, out-of-the-blue cause: duration is short and symptoms are more intense.[2] Panic attacks can occur in children, as well as adults. Panic in young people may be particularly distressing because children tend to have less insight about what is happening, and parents are also likely to experience distress when attacks occur.

Screening tools like Patient Health Questionnaire can be used to detect possible cases of the disorder, and suggest the need for a formal diagnostic assessment.[3]

Panic disorder is a potentially disabling disorder, but can be controlled and successfully treated. Because of the intense symptoms that accompany panic disorder, it may be mistaken for a life-threatening physical illness such as a heart attack. This misconception often aggravates or triggers future attacks (some are called "anticipatory attacks"). People frequently go to hospital emergency rooms on experiencing a panic attack, and extensive medical tests may be performed to rule out other conditions, thus creating further anxiety. There are three types of panic attacks: unexpected, situationally bounded, and situationally predisposed.[4]

Signs and symptoms

Panic disorder sufferers usually have a series of intense episodes of extreme anxiety during panic attacks. These attacks typically last about ten minutes, and can be as short-lived as 1–5 minutes, but can last twenty minutes to more than an hour, or until helpful intervention is made. Panic attacks can wax and wane for a period of hours (panic attacks rolling into one another), and the intensity and specific symptoms of panic may vary over the duration.

In some cases the attack may continue at unabated high intensity, or seem to be increasing in severity. Common symptoms of an attack include rapid heartbeat, perspiration, dizziness, dyspnea, trembling, uncontrollable fear such as: the fear of losing control and going crazy,[5] the fear of dying[6] and hyperventilation. Other symptoms are sweating, a sensation of choking, paralysis, chest pain, nausea, numbness or tingling, chills or hot flashes, faintness, crying[7] and some sense of altered reality.[8] In addition, the person usually has thoughts of impending doom.[9] Individuals suffering from an episode have often a strong wish of escaping from the situation that provoked the attack. The anxiety of Panic Disorder is particularly severe and noticeably episodic compared to that from Generalized Anxiety Disorder. Panic attacks may be provoked by exposure to certain stimuli (e.g., seeing a mouse) or settings (e.g., the dentist's office).[8] Other attacks may appear unprovoked. Some individuals deal with these events on a regular basis, sometimes daily or weekly. The outward symptoms of a panic attack often cause negative social experiences (e.g., embarrassment, social stigma, social isolation, etc.).

Limited symptom attacks are similar to panic attacks, but have fewer symptoms. Most people with PD experience both panic attacks and limited symptom attacks.

Causes

Psychological models

There is no single cause for panic disorder, however, panic disorder has been found to run in families, and suggests that inheritance plays a strong role in determining who will get it.[10] It has also been found to exist as a co-morbid condition with many hereditary disorders, such as bipolar disorder, and a genetic predisposition to alcoholism.

Psychological factors, stressful life events, life transitions, and environment as well as often thinking in a way that exaggerates relatively normal bodily reactions are also believed to play a role in the onset of panic disorder. Often the first attacks are triggered by physical illnesses, major stress, or certain medications. People who tend to take on excessive responsibilities may develop a tendency to suffer panic attacks. Post-traumatic stress disorder (PTSD) patients also show a much higher rate of panic disorder than the general population.

There is some evidence to suggest hypoglycemia, hyperthyroidism, mitral valve prolapse, labyrinthitis, pheochromocytoma and respiratory conditions can cause or aggravate panic disorder.

Prepulse inhibition has been found to be reduced in patients with Panic Disorder.[11]

Many SSRIs also have stimulant side-effects during the beginning of treatment which may exacerbate the condition and have actually caused first-time panic attacks in otherwise healthy individuals being treated for depression.

Substance misuse

Substance abuse is often correlated with panic attacks. The majority of individuals participating in a study determined (63%) of those abusing alcohol reported that alcohol use began prior to onset of panic, and the majority (59%) of those abusing illicit drugs reported that drug use began first. The study that was conducted documented the panic-substance abuse relationship. Substance abuse began prior to onset of panic and substances were used to self-medicate for panic attacks by only a few subjects.[12]

In another study, 100 methamphetamine dependent individuals were analyzed for co-morbid psychiatric disorders; of the 100 individuals, 36% were categorized as having co-morbid psychiatric disorders. Mood and Psychotic disorders were more prevalent than anxiety disorders, which accounted for 7% of the 100 sampled individuals.[13]

Smoking

Tobacco smoking increases the risk of developing panic disorder with or without agoraphobia[14][15] and panic attacks; smoking started in adolescence or early adulthood particularly increases this risk of developing panic disorder.[16][17][18] While the mechanism of how smoking increases panic attacks is not fully understood, a few hypotheses have been derived. Smoking cigarettes may lead to panic attacks by causing changes in respiratory function (e.g. feeling short of breath). These respiratory changes in turn can lead to the formation of panic attacks, as respiratory symptoms are a prominent feature of panic.[16][19] Respiratory abnormalities have been found in children with high levels of anxiety, which suggests that a person with these difficulties may be susceptible to panic attacks, and thus more likely to subsequently develop panic disorder. Nicotine, a stimulant, could contribute to panic attacks.[20][21] However, nicotine withdrawal may also cause significant anxiety which could contribute to panic attacks.

It is also possible that panic disorder patients smoke cigarettes as a form of self-medication to lessen anxiety. Nicotine and other psychoactive compounds with antidepressant properties in tobacco smoke which act as monoamine oxidase inhibitors in the brain can alter mood and have a calming effect, depending on dose.

Caffeine

A number of clinical studies have shown a positive association between caffeine ingestion and panic disorder and/or anxiogenic effects.[22][23] People who have panic disorder are more sensitive to the anxiety provoking effects of caffeine. One of the major anxiety provoking effects of caffeine being an increase in heart rate.[24][25][26][27]

Alcohol and sedatives

About 30% of people with panic disorder use alcohol and 17% use other psychoactive drugs.[28] This is in comparison with 61% (alcohol)[29] and 7.9% (other psychoactive drugs)[30] of the general population who use alcohol and psychoactive drugs, respectively. Utilization of recreational drugs or alcohol generally make symptoms worse.[31] Most stimulant drugs (caffeine, nicotine, cocaine) would be expected to worsen the condition, since they directly increase the symptoms of panic, such as heart rate.

Deacon and Valentiner (2000)[32] conducted a study that examined co-morbid panic attacks and substance use in a non-clinical sample of young adults who experienced regular panic attacks. The authors found that compared to healthy controls, therapeutic alcohol and sedative use was greater for non-clinical participants who experienced panic attacks. These findings are consistent with the suggestion made by Cox, Norton, Dorward, and Fergusson (1989)[33] that panic disorder patients self-medicate if they believe that certain substances will be successful in alleviating their symptoms. If panic disorder patients are indeed self-medicating, there may be a portion of the population with undiagnosed panic disorder who will not seek professional help as a result of their own self-medication. In fact, for some patients panic disorder is only diagnosed after they seek treatment for their self-medication habit.[34]

While alcohol initially helps ease panic disorder symptoms, medium- or long-term alcohol abuse can cause panic disorder to develop or worsen during alcohol intoxication, especially during alcohol withdrawal syndrome.[35] This effect is not unique to alcohol but can also occur with long term use of drugs which have a similar mechanism of action to alcohol such as the benzodiazepines which are sometimes prescribed as tranquilizers to people with alcohol problems.[35] The reason chronic alcohol misuse worsens panic disorder is due to distortion of the brain chemistry and function.[36][37][38]

Approximately 10% of patients will experience notable protracted withdrawal symptoms, which can include panic disorder, after discontinuation of benzodiazepines. Protracted withdrawal symptoms tend to resemble those seen during the first couple of months of withdrawal but usually are of a subacute level of severity compared to the symptoms seen during the first 2 or 3 months of withdrawal. It is not known definitively whether such symptoms persisting long after withdrawal are related to true pharmacological withdrawal or whether they are due to structural neuronal damage as result of chronic use of benzodiazepines or withdrawal. Nevertheless such symptoms do typically lessen as the months and years go by eventually disappearing altogether.[39]

A significant proportion of patients attending mental health services for conditions including anxiety disorders such as panic disorder or social phobia have developed these conditions as a result of alcohol or sedative abuse. Anxiety may pre-exist alcohol or sedative independence, which then acts to perpetuate or worsen the underlying anxiety disorder. Someone suffering the toxic effects of alcohol abuse or chronic sedative use or abuse will not benefit from other therapies or medications for underlying psychiatric conditions. as they do not address the root cause of the symptoms. Recovery from sedative Symptoms may temporarily worsen during alcohol withdrawal or benzodiazepine withdrawal.[40][41][42][43]

Mechanism

There are other researchers looking at some individuals with panic disorder as having a chemical imbalance within the limbic system and one of its regulatory chemicals GABA-A. The reduced production of GABA-A sends false information to the amygdala which regulates the body's "fight or flight response" mechanism and in return, produces the physiological symptoms that lead to the disorder. Clonazepam, an anticonvulsant benzodiazepine with a long half-life, has been successful in keeping the condition in check.[44]

Recently, researchers have begun to identify mediators and moderators of aspects of panic disorder. One such mediator is the partial pressure of carbon dioxide, which mediates the relationship between panic disorder patients receiving breathing training and anxiety sensitivity; thus, breathing training affects the partial pressure of carbon dioxide in a patient’s arterial blood, which in turn lowers anxiety sensitivity.[45] Another mediator is hypochondriacal concerns, which mediate the relationship between anxiety sensitivity and panic symptomatology; thus, anxiety sensitivity affects hypochondriacal concerns which, in turn, affect panic symptomatology.[46]

Perceived threat control has been identified as a moderator within panic disorder, moderating the relationship between anxiety sensitivity and agoraphobia; thus, the level of perceived threat control dictates the degree to which anxiety sensitivity results in agoraphobia.[47] Another recently identified moderator of panic disorder is genetic variations in the gene coding for galanin; these genetic variations moderate the relationship between females suffering from panic disorder and the level of severity of panic disorder symptomatology.[48]

Diagnosis

The DSM-IV-TR diagnostic criteria for panic disorder require unexpected, recurrent panic attacks, followed in at least one instance by at least a month of a significant and related behavior change, a persistent concern of more attacks, or a worry about the attack's consequences. There are two types, one with and one without agoraphobia. Diagnosis is excluded by attacks due to a drug or medical condition, or by panic attacks that are better accounted for by other mental disorders.[49]

Treatment

Panic disorder is a serious health problem that in many cases can be successfully treated, although there is no known cure. Identification of treatments that engender as full a response as possible, and can minimize relapse, is imperative.[50] Cognitive behavioural therapy and Positive Self Talk specific for panic[51] are the treatment of choice for panic disorder. Several studies show that 85 to 90 percent of panic disorder patients treated with CBT recover completely from their panic attacks within 12 weeks.[52] When cognitive behavioral therapy is not an option pharmacotherapy can be used. SSRIs are considered a first line pharmacotherapeutic option.[53][54][55]

Cognitive Behavioral Therapy

Cognitive Behavioral Therapy encourages patients to confront the triggers that induce arouse their anxiety. By facing the very cause of the anxiety, it is thought to help diminish the irrational fears that are causing the issues to begin with. The therapy begins with calming breathing exercises, followed by nothing the changes in physical sensations felt at the start of anxiety entering the body. Many clients are encouraged to keep journals. In other cases, therapists may try and induce feelings of anxiety so that the root of the fear can be identified.[56]

Comorbid clinical depression, personality disorders and alcohol abuse are known risk factors for treatment failure.[57]

As with many disorders, having a support structure of family and friends who understand the condition can help increase the rate of recovery. During an attack, it is not uncommon for the sufferer to develop irrational, immediate fear, which can often be dispelled by a supporter who is familiar with the condition. For more serious or active treatment, there are support groups for anxiety sufferers which can help people understand and deal with the disorder.

Current treatment guidelines American Psychiatric Association and the American Medical Association primarily recommend either cognitive-behavioral therapy or one of a variety of psychopharmacological interventions. Some evidence exists supporting the superiority of combined treatment approaches.[58][59][60]

Another option is self-help based on principles of cognitive-behavioral therapy.[61] Using a book or a website, a person does the kinds of exercises that would be used in therapy, but they do it on their own, perhaps with some email or phone support from a therapist.[62] A systematic analysis of trials testing this kind of self-help found that websites, books, and other materials based on cognitive-behavioral therapy could help some people.[61] The best-studied conditions are panic disorder and social phobia.[61]

Psychotherapy

Panic Disorder is not the same as phobic symptoms, although phobias commonly result from panic disorder.[63] CBT and one tested form of psychodynamic psychotherapy have been shown efficacious in treating panic disorder with and without agoraphobia.[59][64][65] A number of randomized clinical trials have shown that CBT achieves reported panic-free status in 70-90% of patients about 2 years after treatment.[52][66]

Clinically, a combination of psychotherapy and medication can often produce good results, although research evidence of this approach has been less robust. Some improvement may be noticed in a fairly short period of time — about 6 to 8 weeks. Psychotherapy can improve the effectiveness of medication, reduce the likelihood of relapse for someone who has discontinued medication, and offer help for people with panic disorder who do not respond at all to medication.[66]

The goal of cognitive behavior therapy is to help a patient reorganize thinking processes and anxious thoughts regarding an experience that provokes panic. An approach that proved successful for 87% of patients in a controlled trial is interoceptive therapy, which simulates the symptoms of panic to allow patients to experience them in a controlled environment.[66]

Symptom inductions generally occur for one minute and may include:

The key to the induction is that the exercises should mimic the most frightening symptoms of a panic attack, although none of the symptoms listed above are the essence of panic attack—which is pure terrifying panic. Symptom inductions should be repeated three to five times per day until the patient has little to no anxiety in relation to the symptoms that were induced. Often it will take a period of weeks for the afflicted to feel no anxiety in relation to the induced symptoms. With repeated trials, a person learns through experience that these internal sensations do not need to be feared and becomes less sensitized or desensitized to the internal sensation. After repeated trials, when nothing catastrophic happens, the brain learns (hippocampus & amygdala) to not fear the sensations, and the sympathetic nervous system activation fades. However, in real-life situations panic may escalate independently of whether the subject is fearful of the minor symptoms associated with panic. The subject may have no fear of fast heart rate, hyperventilation or derealization, but may nevertheless feel terror, and it is the terror that may cause the other symptoms. Psychiatrists are asking subjects to feel terror but look upon it dispassionately, a situation which would require extraordinary mind control training and not contribute to the subject's quality of life. Meanwhile, there is true danger of blackouts in hyperventilation, heart attacks in racing heart rates, being out of personal control during derealization, and so on.

For patients whose panic disorder involves agoraphobia, the traditional cognitive therapy approach has been in vivo exposure, in which the affected individual, accompanied by a therapist, is gradually exposed to the actual situation that provokes panic.[66]

Another form of psychotherapy which has shown effectiveness in controlled clinical trials is panic-focused psychodynamic psychotherapy, which focuses on the role of dependency, separation anxiety, and anger in causing panic disorder. The underlying theory posits that due to biochemical vulnerability, traumatic early experiences, or both, people with panic disorder have a fearful dependence on others for their sense of security, which leads to separation anxiety and defensive anger. Therapy involves first exploring the stressors that lead to panic episodes, then probing the psychodynamics of the conflicts underlying panic disorder and the defense mechanisms that contribute to the attacks, with attention to transference and separation anxiety issues implicated in the therapist-patient relationship.[67]

Comparative clinical studies suggest that muscle relaxation techniques and breathing exercises are not efficacious in reducing panic attacks.[66] In fact, breathing exercises may actually increase the risk of relapse.[68]

Appropriate treatment by an experienced professional can prevent panic attacks or at least substantially reduce their severity and frequency — bringing significant relief to percent of people with panic disorder.[69] Relapses may occur, but they can often be effectively treated just like the initial episode.

vanApeldoorn, F.J. et al. (2011) demonstrated the additive value of a combined treatment incorporating an SSRI treatment intervention with cognitive behavior therapy (CBT).[70] Gloster et al. (2011) went on to examine the role of the therapist in CBT. They randomized patients into two groups: one being treated with CBT in a therapist guided environment, and the second receiving CBT through instruction only, with no therapist guided sessions. The findings indicated that the first group had a somewhat better response rate, but that both groups demonstrated a significant improvement in reduction of panic symptomatology. These findings lend credibility to the application of CBT programs to patients who are unable to access therapeutic services due to financial, or geographic inaccessibility.[71] Koszycky et al. (2011) discuss the efficacy of self-administered cognitive behavioural therapy (SCBT) in situations where patients are unable to retain the services of a therapist. Their study demonstrates that it is possible for SCBT in combination with an SSRI to be as effective as therapist-guided CBT with SSRI. Each of these studies contribute to a new avenue of research that allows effective treatment interventions to be made more easily accessible to the population.[72]

Medication

Appropriate medications are effective for panic disorder. Selective serotonin reuptake inhibitors are first line treatments rather than benzodiazapines due to concerns with the latter regarding tolerance, dependence and abuse.[73] Although there is little evidence that pharmacological interventions can directly alter phobias, few studies have been performed, and medication treatment of panic makes phobia treatment far easier. Medications can include:

Other treatments

For some people, anxiety can be greatly reduced by discontinuing the use of caffeine.[82] Anxiety can temporarily increase during caffeine withdrawal.[83][84][85]

Epidemiology

Age-standardized disability-adjusted life year rates for panic disorder per 100,000 inhabitants in 2002.
  no data
  less than 10
  10-96.25
  96.25-97.5
  97.5-98.75
  98.75-100
  100-101.25
  101.25-102.5
  102.5-103.75
  103.75-105
  105-106.25
  106.25-107.5
  more than 107.5

It typically begins during early adulthood; roughly half of all people who have panic disorder develop the condition before age 24, especially those subjected to traumatic experiences. However, some sources say that the majority of young people affected for the first time are between the ages of 25 and 30. Women are twice as likely as men to develop panic disorder.[86]

Panic disorder can continue for months or years, depending on how and when treatment is sought. If left untreated, it may worsen to the point where one's life is seriously affected by panic attacks and by attempts to avoid or conceal the condition. In fact, many people have had problems with personal relationships or employment while struggling to cope with panic disorder. Some people with panic disorder may conceal their condition because of the stigma of mental illness. In some individuals, symptoms may occur frequently for a period of months or years, then many years may pass without symptoms. In some cases, the symptoms persist at the same level indefinitely. There is also some evidence that many individuals (especially those who develop symptoms at an early age) may experience symptom cessation later in life (e.g. past age 50).

In 2000, the World Health Organization found prevalence and incidence rates for panic disorder to be very similar across the globe. Age-standardized prevalence per 100,000 ranged from 309 in Africa to 330 in East Asia for men and from 613 in Africa to 649 in North America, Oceania, and Europe for women.[87]

Children

A retrospective study has shown that 40% of adult panic disorder patients reported that their disorder began before the age of 20.[88] In an article examining the phenomenon of panic disorder in youth, Diler et al. (2004)[89] found that only a few past studies have examined the occurrence of juvenile panic disorder. They report that these studies have found that the symptoms of juvenile panic disorder almost replicate those found in adults (e.g. heart palpitations, sweating, trembling, hot flashes, nausea, abdominal distress, and chills).[90][91][92][93][94] The anxiety disorders co-exist with staggeringly high numbers of other mental disorders in adults.[95] The same comorbid disorders that are seen in adults are also reported in children with juvenile panic disorder. Last and Strauss (1989)[96] examined a sample of 17 adolescents with panic disorder and found high rates of comorbid anxiety disorders, major depressive disorder, and conduct disorders. Eassau et al. (1999)[92] also found a high number of comorbid disorders in a community-based sample of adolescents with panic attacks or juvenile panic disorder. Within the sample, adolescents were found to have the following comorbid disorders: major depressive disorder (80%), dysthymic disorder (40%), generalized anxiety disorder (40%), somatoform disorders (40%), substance abuse (40%), and specific phobia (20%). Consistent with this previous work, Diler et al. (2004) found similar results in their study in which 42 youths with juvenile panic disorder were examined. Compared to non-panic anxiety disordered youths, children with panic disorder had higher rates of comorbid major depressive disorder and bipolar disorder.

Children differ from adolescents and adults in their interpretation and ability to express their experience. Like adults, children experience physical symptoms including accelerated heart rate, sweating, trembling or shaking, shortness of breath, nausea or stomach pain, dizziness or light-headedness. In addition children also experience cognitive symptoms like fear of dying, feelings of being detached from oneself, feelings of losing control or going crazy, but they are unable to vocalize these higher order manifestations of fear. They simply know that something is going wrong and that they are very afraid. Children can only describe the physical symptoms. They have not yet developed the constructs to put these symptoms together and label them as fear. Parents often feel helpless when they watch a child suffer. They can help children give a name to their experience, and empower them to overcome the fear they are experiencing[97]

The role of the parent in treatment and intervention for children diagnosed with panic disorder is discussed by McKay & Starch (2011). They point out that there are several levels at which parental involvement should be considered. The first involves the initial assessment. Parents as well as the child should be screened for attitudes and treatment goals, as well as for levels of anxiety or conflict in the home. The second involves the treatment process in which the therapist should meet with the family as a unit as frequently as possible. Ideally all family members should be aware and trained in the process of cognitive behaviour therapy (CBT) in order to encourage the child to rationalize and face fears rather than employ avoidant safety behaviours. McKay & Storch (2011) suggest training/modeling of therapeutic techniques and in session involvement of the parents in the treatment of children to enhance treatment efficacy.[98]

Despite the evidence pointing to the existence of early-onset panic disorder, the DSM-IV-TR currently only recognizes six anxiety disorders in children: separation anxiety disorder, generalized anxiety disorder, specific phobia, obsessive-compulsive disorder, social anxiety disorder (a.k.a. social phobia), and post-traumatic stress disorder. Panic disorder is notably excluded from this list.

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