Panic disorder with agoraphobia or without agoraphobia

The main symptom of a panic disorder is a recurring panic attack. Panic attacks are characterized by sudden intense anxiety, accompanied by at least four autonomic or cognitive symptoms.

A panic attack is characterized by rapid development, anxiety culminates in a few minutes. The panic attack ends just as suddenly, lasting no more than 30 minutes, but a mild anxiety can last even more than an hour.

In DSM-IV, there are three types of panic attacks. Spontaneous panic attacks occur unexpectedly, without precursors, without provoking any factors. Situational panic attacks are triggered by certain frightening incentives or the expectation of their possible appearance. Conventionally (situationally predisposed) panic attacks occupy an intermediate position: they often arise under the influence of a certain stimulus, but this relationship is not always traced. Panic disorder is characterized by spontaneous panic attacks that occur in the absence of any trigger stimuli or situations. Diagnosis of panic disorder is possible if at least two spontaneous panic attacks occur, and at least one of these seizures should be accompanied by anxious anticipation of subsequent seizures or behavioral changes for at least 1 month.

In patients with panic disorder, there are a number of comorbid conditions. Of particular interest are the relationships between panic disorder and agoraphobia. Agoraphobia is characterized by the presence of fear or anxiety associated with visiting places from which it can be difficult to get out. There is no single answer to the question whether agoraphobia is an independent disorder, but there is no doubt that the treatment of agoraphobia is an indispensable component of panic disorder therapy. One of the main problems is the frequency with which agoraphobia occurs without panic disorder and panic attacks. Part of this problem is created by epidemiological data, according to which agoraphobia is ahead of the prevalence of panic disorders. But in this chapter, these two states are considered together, as there is doubt about the validity of these epidemiological data. Virtually all patients with agoraphobia suffer panic attacks, and antipanic therapy can lead to regression of agoraphobia. Even if agoraphobia occurs in the absence of panic attacks, it may be associated with fear of developing panic-like symptoms.

[1], [2], [3], [4], [5], [6], [7]

Pathogenesis of panic disorder with agoraphobia or without agoraphobia

Although the pathogenesis of panic disorder remains largely unclear, there are several theories. This disease is known more than about any other disorder discussed in this chapter. The following sections discuss modern theories that are relevant to the treatment of panic disorder (with or without agoraphobia).

Respiratory theories of panic disorder

One theory suggests that a spontaneous panic attack is a kind of "emergency" reaction that occurs in response to a malfunction in the regulation of breathing. According to this theory, a panic attack was provoked by a lack of breathing through the activation of a hypothetical "choking center" in the brain. The neuroanatomical model linked the development of a panic attack with the hyperactivation of stem structures, which was reflected in changes in respiratory functions, dysfunction of noradrenergic and serotonergic systems. According to this model, the remaining manifestations of panic disorder are associated with impaired functioning of other parts of the brain: for example, anxiety expectations - with dysfunction of limbic structures (eg, tonsils), and restrictive behavior - with disturbances in the prefrontal cortex.

Respiratory theories are based on a number of well-known data noted in the study of adult patients with panic disorder. First, complaints of respiratory failure are one of the most important components of a panic attack clinic. Secondly, people with respiratory diseases suffering from dyspnea have more panic-like symptoms than those without dyspnea. Third, in adults with panic disorder, an increased anxiety reaction is often observed when exposed to agents that stimulate the respiratory center, for example, carbon dioxide, sodium lactate, and doxapram, a stimulant of carotid bodies. Finally, a heightened anxiety reaction is reflected in the physiology of breathing: panic attacks are accompanied by a pronounced increase in ventilation. In patients with panic disorder, a number of violations of the neurogenic regulation of respiration have been detected, including hyperventilation and "chaotic ventilation" in the study of respiration in a special chamber. Although it remains unclear to what extent these respiratory disorders are associated with the severity of anxiety, the fact that similar changes are detected in sleep also indicates that they depend not only on cognitive factors.

The respiratory model of panic disorder has found application in the therapy of this condition. Drugs that effectively block panic attacks induced by the stimulation of the respiratory center are also effective in routine panic attacks, while drugs effective for generalized anxiety disorder (but not for panic disorder) do not block panic attacks induced by the stimulation of the respiratory center. There are data on the hereditary nature of violations of breathing regulation. In mentally healthy relatives of patients with panic attacks, a pathological reaction to the inhalation of carbon dioxide was detected. Given the reliability and good reproducibility of these results, the researchers continue to investigate the relationship between panic disorder and breathing regulation.

Vegetative theories of panic disorder

Assumptions about the close connection between the autonomic nervous system and panic disorder were expressed quite a long time ago. In earlier studies, there was a trend toward accelerating the heart rate in patients with panic disorder, especially in the laboratory. This result was explained by the influence of personal anxiety on the patient's status, since such changes in cardiac activity were less often found in natural conditions. More recent studies were based on the study of cardiac parameters of the interaction of parasympathetic and sympathetic systems and reactions to noradrenergic drugs. These data confirm that panic disorder may occur due to the delicate dysfunction of the sympathetic nervous system, the parasympathetic nervous system, or the disruption of interaction between them.

The most reliable evidence of parasympathetic dysfunction in patients with panic disorder was obtained in the study of heart rate variability. Although the results of these studies did not always coincide, in adults with panic disorder there was a tendency to reduce the high-frequency component of the spectral power of the variability of the cardiointervals, indicating a lack of parasympathetic influence. However, significantly more often when studying the variability of cardiointervals, there are signs of imbalance between the sympathetic and parasympathetic systems with a predominance of sympathetic influence. Panic disorder is associated with an increase in the ratio of the power of low-frequency and high-frequency components of the variability of the cardiointervals. This increased ratio is particularly evident in situations where sympathetic activity is enhanced, for example, with an orthostatic test or with the administration of yohimbine. Preliminary data indicate that the acceleration of the heart rhythm during a panic attack is due to the weakening of parasympathetic influences.

However, the significance of these findings very significantly limits their non-specificity. Symptoms of weakening parasympathetic influences in the analysis of heart rate variability are revealed not only in panic disorder, but also in other mental illnesses, for example, major depression or generalized anxiety disorder.

The role of the noradrenergic system in panic disorder is also investigated with the help of neuroendocrinological methods. The most conclusive results were obtained with the help of clonidine - a selective agonist of alpha2-adrenergic receptors. In adults with panic disorder, the growth hormone secretion curve was smoothed in response to the administration of clonidine, indicating a decrease in the sensitivity of hypothalamic alpha-1 adrenergic receptors. Since such a response persists with the successful treatment of panic disorder, it can be considered a marker of predisposition to this disease. In patients with panic disorder, an increase in blood pressure and a level of 3-methoxy-4-hydroxyphenylglycol (MHPG) in response to the administration of clonidine is also detected. The obtained data may indicate a disruption in the functioning of the hypothalamic-pituitary-adrenal axis, due to a violation of its interaction (separation) with the noradrenergic system. Data from the clonidine test indicate a disruption in the functioning of the noradrenergic system, more likely by the type of disregulation, rather than by the type of hyperactivity or hypoactivity.

In panic disorder, a more chaotic MHPG response is observed in response to stimulation of alpha2-adrenergic receptors, but on the background of successful treatment, a normal reaction in the form of a decrease in the level of MHPG in response to the administration of clonidine occurs. Adult patients with panic disorder exhibit an increase in anxiety in response to yohimbine and alpha2-adrenoreceptor agonists that stimulate locus ceruleus. These data, as well as the results of the study of heart rate variability, indicate the possible role of vegetative regulation disorders in the pathogenesis of panic disorder.

However, the results presented are also not completely specific: smoothing of the growth hormone secretion curve in response to the administration of clonidine is detected not only in panic disorder, but also in case of major depression, generalized anxiety disorder and social phobia. Moreover, in adults with posttraumatic stress disorder there is an increased anxious reaction to yohimbine, while with a large depression and generalized anxiety disorder, a normal response to yohimbine is revealed.

Serotonin theory of panic disorder

The most convincing data on the role of serotonin in the pathogenesis of panic disorder are obtained in pharmacological studies. Separate reports from several researchers that patients with panic disorder are predisposed to the development of anxiety at the beginning of treatment with selective inhibitors of reuptake were subsequently confirmed in more systematic studies.

Although the results did not always coincide, the study of neuroendocrine reactions in response to the administration of serotonergic drugs such as fenfluramine, iZapiron, meta-chlorphenyl finerinazine (mCPP) revealed definite changes in patients with panic disorder. The most impressive result was a change in the secretion of cortisol in response to the administration of fenfluramine and mCPP. Patients with panic disorder also showed a change in the serotonin-associated platelet protein, although these results were inconsistent. It was suggested that the panic disorder is related to the production of autoantibodies to xerotonin.

In some studies on the role of serotonin in the pathogenesis of panic disorder, the importance of the interaction between serotonergic and other neurotransmitter systems was emphasized. In particular, the close relationship between serotonergic and noradrenergic systems suggests a link between dysfunction of the serotonergic system and a violation of autonomic regulation in panic disorder. Thus, selective serotonin reuptake inhibitors can reduce the symptoms of panic disorder indirectly, through an effect on the noradrenergic system. This can be proved by the fact that fluoxetine, which is a selective inhibitor of serotonin reuptake, can normalize a chaotic MHPG reaction to the administration of clonidine in patients with panic disorder.

Conditional-reflex theory of panic disorder

The development of a conditioned reflex phobic reaction in experimental animals makes it possible to create a laboratory model of anxiety. To do this, neutral conditional stimuli (for example, a flash of light or sound) were paired with negative or unconditional stimuli, for example, electric shock. As a result, in response to the conditioned stimulus, the same physiological and behavioral reaction occurred, as on the unconditional stimulus. The neuronal circle associated with the elaboration of this conditioned reflex has been studied. This circle includes somatosensory pathways resulting from exteroceptors to the thalamus and the central core of the amygdala. The central nucleus of the amygdala also receives cortical projections capable of regulating the functioning of the subcortical circle, which mainly ensures the development of a conditioned reflex phobic reaction. Of particular importance are projections from the gigocampal region and the prefrontal cortex. It is assumed that any alarming reaction, including a panic attack, occurs as a result of the interaction of the amygdala with stem structures, basal ganglia, the hypothalamus and cortical pathways.

The theory of conditioned reflex fear was proposed in relation to the panic disorder LeDoux (1996). According to this theory, internal stimuli (for example, increased blood pressure or changes in breathing) are considered as conditional stimuli capable of triggering a panic attack. Thus, a panic attack can occur as a result of the activation of the neural pathways that provide the formation of a conditioned reflex phobic reaction in response to normal fluctuations in physiological functions. Clinical studies indicate that the brain structures that provide the realization of the conditioned reflex phobic reaction in experimental animals can also be used in humans. This theory was also confirmed by neuroimaging data, which revealed in patients with panic disorder the signs of dysfunction of structures projected onto the amygdala, in particular the prefrontal cortex and the hippocampus. The fact that a conditioned reflex can be elaborated on the basis of a respiratory and physiological response to the inhalation of carbon dioxide also supports this model. Agoraphobia can also be considered as a form of conditioned reflex phobic reaction, while panic attacks play the role of unconditional stimulus in the formation of fear. To study the mechanisms of development of panic attacks, a model of an affectively enhanced startle reflex was proposed, but the results of the study proved to be ambiguous.

[8], [9], [10], [11], [12], [13], [14], [15]

Cognitive theories of panic disorder

Most specialists recognize the existence of a strong biological component underlying the panic attacks, but they differ in their views on the causes of this condition. Some believe that the cause may be cognitive factors.

It is suggested that a number of cognitive factors influence the development of panic attacks. It is noted that patients with panic disorder are characterized by increased anxiety sensitivity and a lower threshold of perception of signals from internal organs. In favor of this theory is evidenced by the fact that people with anxious sensitivity report a more significant number of symptoms when triggering an anxiety exercise. At the same time, this theory was not significantly confirmed in experiments with biological feedback, when subjects were able to control their physiological parameters, for example, the heart rhythm.

According to another theory, close to the above mentioned, patients with panic disorder have a tendency to "catastrophize" (catastrophic thinking), especially in situations that they are not in a position to fully control. This theory is confirmed by studies showing that learning to control the situation affects the sensitivity to stimuli provoking panic attacks.

According to some theories, the experience of separation from a loved one, especially in childhood, predisposes to the development of panic disorder. In favor of these theories are evidence of a number of studies, which, however, not always succeeded in reproducing. In a recent study, it was noted that separation from a person who personified safety affects the occurrence of panic attacks in response to the inhalation of carbon dioxide. Thus, there is a tendency to integrate modern versions of cognitive theories and the biological theories described above.

[16], [17], [18], [19], [20], [21], [22], [23]

The course of a panic disorder with agoraphobia or without agoraphobia

Panic disorder usually begins at a youthful or young age, although cases with the onset in childhood and adulthood are described. There are only approximate data on the course of panic disorder. More reliable data can only be obtained through prospective epidemiological studies, whereas retrospective and clinical studies often produce inaccurate data that is difficult to interpret. Data obtained in retrospective and clinical studies indicate that panic disorder has a fluctuating course with a variable outcome. Approximately one-third or half of patients on subsequent observation are mentally healthy, and the majority lead a relatively normal life, despite fluctuations in the severity of symptoms or the presence of relapses. Usually with chronic disorders, there is an alternation of exacerbations or remissions, and not a constant level of symptoms. Clinicians often observe patients in the onset of a disorder or during periods of exacerbation. Therefore, when examining a patient with panic attacks, it is especially important to obtain detailed anamnestic information about the preceding symptoms. It is necessary to find out about the results of the conducted surveys, calls for "first aid" or emergency hospitalizations for unexplained somatic symptoms, as well as about drugs or narcotic substances that the patient may have used.

Diagnostic criteria for panic attack

A clearly defined period of pronounced fear or discomfort, accompanied by at least four of the following symptoms that appear suddenly and reach a peak within 10 minutes

1. Palpitation, a feeling of heart pounding or heart rate increase
2. Sweating
3. Trembling or chills
4. Shortness of breath or shortness of breath
5. Sensation of suffocation
6. Pain or discomfort in the chest
7. Nausea or discomfort in the abdomen
8. Feeling dizzy and unstable
9. Derealization (a sense of unreality of what is happening) or depersonalization (alienation from oneself)
10. Fear of losing control or going insane
11. Fear of dying
12. Paresthesia
13. Waves of heat or cold

Note: a panic attack does not have a special code; a disease is identified in which panic attacks are noted (for example, 200.21 - panic disorder without agoraphobia).

[24], [25], [26], [27], [28], [29], [30]

Diagnostic criteria of agoraphobia

• Anxiety in connection with getting into places or situations, from which it can be difficult (or uncomfortable) to get out or where it can not be helped in case of an unexpected or conditionally-situation panic attack or panic-like symptoms. Fear of agoraphobia is usually associated with certain groups of situations, including being alone outside the home, staying in a crowd, standing in line, being on a bridge, riding a bus, train or car.

If the patient avoids only one or more specific situations, then a specific phobia should be diagnosed; if avoidance is limited only by communication situations, diagnose social phobia

• The patient avoids certain situations (for example, restricts walking routes), or if they get into them, he experiences severe discomfort or anxious fears about the possible development of a panic attack or panic-like symptoms, or insists on accompanying another person
• Anxiety or phobic avoidance can not be better explained by the presence of other psychiatric disorders, such as social phobia (if the patient avoids only public situations and is afraid of being embarrassed), specific phobias (if the patient avoids only one specific situation, for example, trips to lift), obsessive-compulsive disorder (for example, if avoidance is caused by obsessive fears of contamination or contamination), post-traumatic stress disorder (with avoidance of stimuli associated with the loi trauma) or separation anxiety disorder (for the avoidance of possible separation from home or relatives)

Note: agoraphobia does not have a special code; the disease in which agoraphobia occurs (for example, 300.21 - panic disorder with agoraphobia or 200.22 - agoraphobia without panic disorder) is coded.

[31], [32], [33], [34], [35], [36], [37]

Differential diagnosis of panic disorder

Diagnosis begins by carefully identifying the symptoms described above. This should take into account the possibility of other diseases that can cause similar symptoms. Like other anxiety disorders, panic disorder is often combined not only with agoraphobia, but also with other anxiety and depressive mental disorders. Comorbid conditions include specific and social phobias, generalized anxiety disorder, major depression, drug addiction, bipolar disorder, suicidal behavior. The high degree of comorbidity between anxiety and depressive disorders, apparently, can partly be explained by the characteristics of the contingent of patients being referred to specialists, but the comorbidity between these states is also revealed in epidemiological studies.

Panic disorder with or without agoraphobia should be differentiated with these comorbid conditions. First of all, it is necessary to establish whether the seizures are spontaneous or provoked by a specific situation, which the patient fears. Spontaneous panic attacks patients describe as having happened "in the midst of full health" or "like a bolt from the blue". At the same time, in a patient with a social phobia, a panic attack may occur before a public appearance, in a patient with posttraumatic stress disorder, an attack can be triggered by overwhelmed painful memories, and in a patient with a specific phobia - by falling into a specific situation that causes him fear.

Having established the spontaneous nature of panic attacks, their frequency and severity should be clarified. Single spontaneous panic attacks are often found in adults, but the diagnosis of panic disorder is made only in the presence of multiple repeated panic attacks. The diagnosis is confirmed by the apparent anxiety that the patient is experiencing in connection with the attacks, and he either should have anxious fears about a possible recurrence of attacks, or restrictive behavior should be identified, with the aim to reduce the possible adverse effects of seizures. Differential diagnosis with generalized anxiety disorder is also complicated. Classical panic attack is characterized by a rapid onset and short duration (usually no more than 10-15 minutes) - this is the main difference from a generalized anxiety disorder, in which anxiety builds up and weakens more slowly.

However, this difference is not always easy to identify, because after a panic attack, there is sometimes a diffuse alarm that can regress slowly. Severe anxiety can occur with many mental illnesses, including psychoses and affective disorders, but it is quite difficult to differentiate panic disorder from other psychopathological conditions. The main thing in differential diagnosis is the analysis of the course of psychopathological symptoms. If repeated panic attacks occur only against the background of another mental disorder, the treatment should be directed, first of all, to the underlying disease. But in this case, you should choose the drugs in such a way that they are effective and with panic disorder. For example, panic attacks may occur during episodes of major depression in which tricyclic antidepressants, monoamine oxidase inhibitors or selective serotonin reuptake inhibitors are prescribed; all these drugs are effective in panic disorder. As a rule, panic disorder should be diagnosed only if repeated panic attacks can not be attributed to another patient suffering from a mental disorder.

Panic disorder (with or without agoraphobia) should also be differentiated from somatic diseases, which may manifest similar symptoms. Panic attacks can occur with a variety of endocrine diseases, including hypothyroidism, thyrotoxicosis, hyperparathyroidism, pheochromocytoma. Episodes of hypoglycemia in insulinoma are also accompanied by panic-like symptoms and other signs of damage to the nervous system. In such patients, a thorough physical examination of the systems and organs, a biochemical blood test, endocrinological tests usually reveal signs of endocrine dysfunction. Although these conditions can cause almost the same symptoms as idiopathic panic disorder, extremely rarely endocrine dysfunction is not accompanied by other somatic manifestations. Symptoms of panic disorder can also occur with organic pathology of the central nervous system, including epilepsy, vestibulopathy, tumors, and also under the influence of drugs or narcotic substances. A thorough examination can reveal signs of a neurological disease. Electroencephalography (EEG) and neuroimaging (computed tomography or magnetic resonance imaging) are not shown in all cases, however, in case of suspected neurologic disease, these methods, as well as neurologic consultation, should be included in the survey complex. So, if a panic attack is preceded by an aura, and after it confusion remains, then a thorough neurological examination and EEG carrying out are necessary. With newly discovered neuropsychological disorders or focal neurological symptoms, neurologist consultation is required. Diseases of the heart and lungs, including heart rhythm disturbances, obstructive bronchopulmonary diseases, bronchial asthma, can cause vegetative symptoms and growing anxiety, which can be difficult to distinguish from manifestations of panic disorder. Correct diagnosis in these cases is helped by signs of a physical illness.

[38], [39], [40], [41], [42], [43], [44], [45], [46]