The cardinal feature of panic disorder is the sudden, unexpected, and often overwhelming feeling of terror and apprehension accompanied by somatic symptoms in multiple organ systems such as dyspnea, palpitations, and faintness. The symptoms and signs of panic disorder are similar to those occurring during intense physical exertion or in a life-threatening situation.
Incidence, and epidemiology
Panic disorder is estimated to occur in 1 to 2 percent of the population, with women outnumbering men two to one. The most frequent age of onset of panic attack is the late teen years and early twenties. Panic disorders tend to be familial, and both panic disorder and affective disorder often coexist in the same family. If an individual has a diagnosed panic disorder, up to 18 percent of first-degree relatives also will have panic disorder. Furthermore, twin studies demonstrate a greater incidence in monozygotic twins, suggesting that panic anxiety may have a genetic basis.
A typical panic attack often begins abruptly and without warning while a patient is involved in a relatively nonthreat-ening and nonstressful activity, like entering a store, driving a car, or sitting at a desk working. The patient becomes flushed, lightheaded, and sweaty and is overwhelmed by feelings of terror, apprehension, and impending doom. Dyspnea may occur with a subjective sense of choking or smothering, and palpitations or chest pain are often so severe that patients believe they are having a heart attack or are dying. The symptoms of panic attacks usually peak in less than 10 min and resolve in 20 to 30 min. Most patients experiencing their first panic attack obtain help, sometimes going to a doctor’s office or emergency room, but the fear has usually subsided by this time. Fatigue or exhaustion frequently follows a panic attack, and the patient may sleep.
After repeated panic attacks, most patients develop some degree of anticipatory anxiety and try to avoid those situations that have been paired with panic attacks in the past. Some patients develop agoraphobia—an irrational fear of being alone or in public places. Without effective treatment, the course of panic attacks and agoraphobia leads to an increasingly restricted life-style marked by preoccupation with avoiding those situations that might trigger an attack. Cases of severe panic disorder with agoraphobia may result in patients remaining house-bound for one or more decades, convinced that leaving the house will induce an attack.
Other complications of panic disorder include major depressive syndrome, higher death rates from both suicide and cardiovascular disease, and drug and alcohol dependency. Losses from unemployment and health care costs are estimated to exceed $100 million a year.
Lactate infusions precipitate panic attacks in vulnerable individuals, although at present this is only used as a test in research paradigms. One study employing positron emission tomography demonstrated a decreased rate of blood flow in the left parahippocampus during panic attacks.
Many patients with panic disorder complain of chest pain, cardiac extrasystoles, and palpitations. The diagnostic challenge is to differentiate anxiety with cardiovascular symptoms from the organic diseases it mimics. Because there may be an increased prevalence of mitral valve prolapse in patients with panic disorder this condition should be investigated; however, in the vast majority of patients wtih panic disorder, no significant cardiac pathology is ever found.
Other diagnostic possibilities include both hyperthyroidism and hypothyroidism, a catecholamine-secreting pheochromocytoma, complex partial seizures, and hypoglycemia. Drug ingestions (amphetamine, cocaine, caffeine, sympathomimetic nasal decongestants) and drug withdrawal (alcohol, barbiturates, opiates, minor tranquilizers) may produce symptoms that simulate panic attacks.
Etiology and pathophysiology
The etiology of panic disorders is uncertain and involves an interplay of multiple psychological and biologic determinants.
In the psychodynamic model, anxiety is considered to be a response to the threatened emergence into consciousness of painful, unacceptable thoughts, impulses, or desires, physiologic factors Clinical and experimental evidence point to the involvement of noradrenergic neurons, particularly those projecting rostrally from the locus coeruleus in the upper brainstem, in the pathophysiology of panic disorder. Three lines of evidence suggest that hyperactivity of noradrenergic pathways may play a role in the pathogenesis of panic. First, the clinical manifestations of panic attacks are similar to those induced by sudden, massive stimulation of beta-adrenergic receptors. Second, isoproterenol hydrochloride, a beta agonist, and yohimbine, an alpha-adrenergic receptor antagonist that increases noradrenergic function, produce signs and symptoms that mimic panic attacks. Third, clinical studies support a role for noradrenergic beta blockers, such as propranolol, in successful treatment of pathologic anxiety.
Another avenue of investigation is based on the finding that infusions of sodium lactate into patients with a history of panic disorder often provoke a panic attack indistinguishable from a spontaneous one. Normal subjects without a history of panic disorder are unaffected. In addition, patients whose panic attacks are controlled by antidepressants are protected against lactate-induced panic attacks. Although the mechanism of lactate’s effect is unclear, the findings appear to have diagnostic usefulness and provide a good model of anxiety for further clinical investigation.
Overall, the evidence suggests that the main contribution to panic disorder may be a genetic vulnerability to a biologic disease state. Over time, panic attacks may become associated with environmental events that by themselves are able to elicit symptoms. The particular constellation of environmental stimuli that precipitate panic attack may be influenced by past experience or particular psychological conflicts. A full understanding of the etiology of anxiety probably will require knowledge of a combination of genetic, biologic, and psychological factors.
A comprehensive treatment program combines both pharmacologic and psychotherapeutic approaches. The first step is to block the attacks pharmacologically, usually with tricyclic antidepressants or monoamine oxidase inhibitors (see Chap. 364). These drugs have 80 to 90 percent effectiveness in the treatment and prevention of spontaneous panic attacks. New antianxiety medications such as alprazolam given in high dose are as effective as antidepressants, have fewer side effects, and work within 1 or 2 days. Other benzodiazepines have not proved efficacious. Antidepressant medication may take 4 to 6 weeks before being effective. Beta blockers, e.g., propranolol or atenolol, may block the peripheral manifestations of the panic attacks but have proved ineffective in preventing the psychic fear or panic and may also predispose to or worsen depressive symptomatology. Clonidine may also block panic manifestations, but its efficacy is usually only transient. Relapse is common on discontinuance of pharmacotherapy.
For some patients with panic disorder, particularly those with debilitating agoraphobia, psychotherapy is indicated. The exact form of psychotherapy needed is controversial, but approaches that seek to understand the anxiety and encourage the patient to confront the feared situations are the most effective.