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Panic disorder
Classification and external resources

The Scream (Norwegian: Skrik) an Expressionist painting by Norwegian artist Edvard Munch depicts an episode of extreme anxiety that Munch felt.
ICD-10 F41.0
ICD-9 300.01, 300.21
OMIM 167870
DiseasesDB 30913
MeSH D016584

Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change 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, although many with panic disorder also suffer from agoraphobia.

Contents

Background

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. People frequently go to hospital emergency rooms when they are having panic attacks, and extensive medical tests may be performed to rule out these other conditions, thus creating further anxiety. Nonetheless, Coryell et al. found death rates in panic disorder patients exceeded those in the general population. In their study, 20% of deaths in 113 former psychiatric inpatients with panic disorder followed 35 years later were suicides; however, due to the co-morbidity of anxiety disorders, it is unclear whether panic disorder was the main cause of suicide. This study also found that men with panic disorder had twice the risk of cardiovascular mortality compared to men in the general population. Effective treatment of panic disorder has been shown to offset costs of medical care by as much as 94%.[1]

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, but can be as short-lived as 1–5 minutes and last as long as twenty minutes or until medical intervention. However, 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. Common symptoms of an attack include rapid heartbeat, perspiration, dizziness, dyspnea, trembling, uncontrollable fear, hyperventilation, etc. 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.). As many as 36% of all individuals with panic disorder also have agoraphobia.[1]

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

There is no single cause for panic disorder, but one thing that is certain is that panic disorder has been found to run in families, and this may mean that inheritance plays a strong role in determining who will get it. 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, environment, and 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 and pheochromocytoma can cause or aggravate panic disorder.

Prepulse inhibition has been found to be reduced in patients with Panic Disorder.[2]

Stimulants are a rather common cause for panic attacks. An excess of common stimulants such as caffeine. 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.

Flöttmann describes the genesis of panic psychodynamicly. Panic is a stress symptom. Fear is characteristic of each developmental stage because of feeling of guilt or symbiotic binding. Floating fear or panic stands for the parental stressing call: "Come back to me. You'll panic in your life, you'll have fear of sexuality, fear of separation from me, of being autonomous, and you'll have fear in any situation in your life! You'll feel anxiously, if you do anything that is separating you from mother or father. Don't grow up!" It is the panic that appears in any developmental moment of life.[3]

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[2].

Mediators and Moderators of Panic Disorder

Statistically speaking, three criteria are required to identify a mediating variable: First, the independent variable must be statistically associated with the predicted mediator. Second, the predicted mediator must be statistically associated with the dependent variable. Finally, when statistically controlled for in the presence of the mediator, the association between the independent variable and dependent variable must become non-significant (or be significantly reduced in size). A moderating variable is identified when the interaction between the independent variable and the predicted moderator is significant when predicting the outcome variable [4].

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 [5]. 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 [6].

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 [7]. 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 [8].

Substance abuse and panic disorder

A growing body of evidence exists that shows a link between substance abuse and panic disorder.

Smoking

Several studies have found that cigarette smoking increases the risk of panic attacks and panic disorder in young people.[9] [10][11] 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.[9][12] 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.[13][14] However, nicotine withdrawal may also cause significant anxiety which could contribute to panic attacks.

Alcohol and sedatives

About 30% of people with panic disorder use alcohol and 17% use other psychoactive drugs.[15] This is in comparison with 61% (alcohol)[3] and 7.9% (other psychoactive drugs) [4] of the general population who use alcohol and psychoactive drugs, respectively. Utilization of recreational drugs or alcohol generally make symptoms worse (American Psychiatric Association: Practice guideline for the treatment of patients with panic disorder.[16] 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. Cannabis commonly precipitates panic in panic patients.

Deacon and Valentiner (2000)[17] 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)[18] 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.[19]

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.[20] 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.[21] The reason chronic alcohol misuse worsens panic disorder is due to distortion of the brain chemistry and function.[22][23][24]

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.[25]

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.[26][27][28][29] The World Council of Anxiety does not recommend benzodiazepines for the long term treatment of anxiety disorders due to a range of problems associated with long term use of benzodiazepines including tolerance, psychomotor impairment, cognitive and memory impairments, physical dependence and a benzodiazepine withdrawal syndrome upon discontinuation of benzodiazepines.[30]

Diagnosis

The DSM-IV-TR diagnostic criteria for panic disorder require unexpected, recurrent panic attacks, followed in at least once 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.[31]

Treatment

Identification of treatments that engender as full a response as possible, and can minimize relapse, is imperative.[32] Cognitive behavioural therapy is the treatment of choice for panic disorder. When cognitive behavioural therapy is not an option pharmacotherapy can be used. SSRIs are considered a first line pharmacotherapeutic option.[33][34]

In addition, people with panic disorder may need treatment for other emotional problems. Comorbid clinical depression, personality disorders and alcohol abuse are known risk factors for treatment failure.[35]

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.[36][37][38]

Psychotherapy

Phobic symptoms are often resistant to pharmacological interventions. CBT and one tested form of psychodynamic psychotherapy have been shown efficacious in treating panic disorder with and without agoraphobia.[37][39][40] A number of randomized clinical trials have shown that CBT achieves panic-free status in 70-90% of patients.[41]

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.[41]

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.[41]

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. 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.

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.[41]

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.[42]

Comparative clinical studies suggest that muscle relaxation techniques and breathing exercises are not efficacious in reducing panic attacks.[41] In fact, breathing exercises may actually increase the risk of relapse.[43]

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.[44] Relapses may occur, but they can often be effectively treated just like the initial episode.

Medication

There is little evidence that pharmacological interventions can alter phobias, and few studies have been performed. Medications can be used to treat panic disorder. Medications can include:

  • Antidepressants (SSRIs, MAOIs, tricyclic antidepressants): these are taken regularly every day, and alter neurotransmitter configurations which in turn can help to block symptoms. Although these medications are described as "antidepressants", nearly all of them — especially the tricyclic antidepressants — have anti-anxiety properties, in part, due to their sedative effects. SSRIs have been known to exacerbate symptoms in panic disorder patients, especially in the beginning of treatment and have even provoked panic attacks in otherwise healthy individuals. SSRIs are also known to produce withdrawal symptoms which include rebound anxiety and panic attacks. Comorbid depression has been cited as imparting the worst course, leading to chronic, disabling illness [45][46].
  • Anti-anxiety drugs (benzodiazepines): Use of benzodiazepines for panic disorder is controversial with opinion differing in the medical literature. Some experts recommend benzodiazepines as a long term treatment strategy.[47][48][49][50] Other experts believe that benzodiazepines are best avoided due to the risks of the development of tolerance and physical dependence.[51] The National Institute for Clinical Excellence concluded that benzodiazepine class of drugs are not effective in the long term and only recommend their short-term use in the treatment of panic disorder.[52] The World Federation of Societies of Biological Psychiatry, say that benzodiazepines should not be used as a first line treatment option but are an option for treatment resistant cases of panic disorder.[53]

Despite increasing focus on the use of antidepressants and other agents for the treatment of anxiety as recommended best practice, benzodiazepines have remained a commonly used medication for panic disorder.[54][55]

Epidemiology

Disability-adjusted life year 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

Panic disorder is a serious health problem that in many cases can be successfully treated, although there is no known cure. It typically strikes in early adulthood; roughly half of all people who have panic disorder develop the condition before age 24, especially if the person has been subjected to a traumatic experience. 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.[56]

Panic disorder can continue for months or even years, depending on how and when treatment is sought. If left untreated, it may worsen to the point where the person'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 friends and family or employment while struggling to cope with panic disorder. Some people with panic disorder may begin to lie to 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 symptom-free. In others, 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 a cessation of symptoms naturally later in life (i.e. past age 50).[citation needed]

Panic disorder in children

A retrospective study has shown that 40% of adult panic disorder patients reported that their disorder began before the age of 20.[57] In an article examining the phenomenon of panic disorder in youth, Diler et al. (2004)[58] 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).[59][60][61][62][63] The anxiety disorders co-exist with staggeringly high numbers of other mental disorders in adults.[64] The same comorbid disorders that are seen in adults are also reported in children with juvenile panic disorder. Last and Strauss (1989)[65] 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)[61] 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.

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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