This article will utilize the panic attack as a model for better insight into all of the anxiety disorders. If one can understand the symptomatology and characteristics of a panic attack, one can apply this knowledge to all of the anxiety disorders if certain modifications and limitations of this model are considered.

In a panic attack, a message of misperceived, severe danger is sent from the brainstem area to several other areas of the brain, including the cortex. There the message is intercepted as an acute lack of oxygen in the body, prompting a sense of physiological emergency and imminent threat to life. In fact, however, this message is incorrect; physiological sensors have misinterpreted the amount of carbon dioxide (CO₂) in the bloodstream (as “too much,” when levels are normal) and consequently misinterpreted the amount of oxygen O₂ in the bloodstream (as “too low,” when levels also are normal). In a panic attack, sensors have assessed that conditions in the body will soon be incompatible with life; thus, the sensors have sent emergency requests to other organs to respond to the “emergency.” As a result, the body attempts to (1) obtain more oxygen by increasing the depth and rate of breathing, (2) disperse oxygen to all parts of the body by increasing heart rate and volume, (3) prevent overheating the body by increasing perspiration, and (4) prepare the body for action by shifting blood flow away from normal vegetative functions and toward the muscles.

Despite the body’s misguided shift into physiological emergency preparedness, carbon dioxide and oxygen levels are normal. This misperception is accompanied by massive release of the neurotransmitters norepinephrine (NE) and epinephrine (E) to help the body prepare for this “emergency”…none of which is needed. This aberrant signal, or CO₂ hypersensitivity, is also known as the suffocation false-alarm theory. The false signal regarding the body’s CO₂/O₂ balance can occur anytime, such as when one is eating, relaxing, working, sleeping, or doing any other human activity, whether safe or dangerous, stressful or relaxing.

Panic Disorder (With and Without Agoraphobia)

Panic disorder (PD) is defined as a condition in which recurrent, unexpected panic attacks occur, followed by at least one month’s duration of persistent concern about having more attacks, or worry about the effects of having a panic attack (e.g., having a heart attack or “going crazy”) or a major change in behavior because of the attacks. The attacks are not related to the direct effects of a drug/medication or a known medical condition or accounted for by another known psychiatric disorder.

A number of possible medical conditions must be considered in the differential diagnosis of panic disorder. Anemia, dysrhythmias, asthma, transient ischemic attacks, and hyperthyroidism constitute a few of these conditions. Drugs capable of inducing panic attacks include most central nervous system (CNS) stimulants such as cocaine, amphetamines, and methylphenidate, as well as all antidepressants. Caffeine, nicotine, hallucinogens, and bronchodilators, such as albuterol, can also produce a panic attack. Nonprescription medications such as pseudoephedrine (found in decongestants) and ephedrine (found in herbal products) can also cause a panic attack.

The proposed hypotheses for the etiology of panic disorder include possible dysregulation of the locus ceruleus, hypersensitivity of 5-HT autoreceptors, abnormal cholecystokinin function,and the CO2 hypersensitivity theory presented earlier in this article.

Characteristics of panic disorder occur more frequently in women and have a bimodal age of onset, with the first peak occurring in late adolescence and the second one in the patient’s mid-30s.Patients with untreated panic disorder have been found to have increased rates of depression. Suicide attempts have been reported in 12% of patients with panic attacks and 20% of those with panic disorder.

Patients with panic disorder can develop agoraphobia, which is avoidance and anxiety about situations or places from which escape may be difficult or embarrassing, or help would be unavailable if a panic attack were to occur. Patients typically avoid these situations partially or completely or they may tolerate and endure them with extreme anxiety.

* Researchers at Detroit’s Wayne State University randomized 168 patients with panic disorder to receive either sertraline or a placebo for 10 weeks to collect data.

* Found that the average number of panic attacks suffered weekly by patients treated with sertraline dropped 88%, compared to a 53% drop seen in placebo recipients. – authors further note that patients treated with sertraline showed significant improvements in measures of quality of life enjoyment and on personal assessments of the severity of their illness.

* The report notes that sertraline treatment was not associated with “jitteriness,” which is a common side-effect of older antidepressants used to treat panic disorder.

New York, London: The Guilford Press; 1997. 261 pp. with index

ISBN 1-57230-237-2

Anxiety is a profound human experience. Anxiety disorders are universal in human societies, although the diagnostic patterns vary over time and from one place to another. This volume describes some culturally bound anxiety syndromes, but dwells on the diagnostic categories of the Diagnostic and Statistical Manual of Mental Disorders, third (DSM-III), third revised (DSM-III-R) and fourth (DSM-IV) editions. This manual provides diagnostic criteria for panic disorder, phobias, obsessive-compulsive disorder, post-traumatic stress disorder and the generalized anxiety disorder. Twenty-seven prominent psychiatrists, psychologists and experts from related fields contributed to this volume, offering guidelines for diagnosis and culturally informed treatment.

The first part of the book deals with general issues in the cross-cultural treatment of anxiety disorders. The second part of the volume deals with the treatment of specific ethnic groups in the US, including Hispanic-, Caribbean-, Asian- and African-Americans, as well as Orthodox Jews, and Asian-Indian-Americans. The third part of the book examines the relations between psychopharmacology and ethnicity, and modern aspects of the clinical and research agenda in culture and anxiety.

P.J. Guarnaccia addresses risk factors, symptoms of distress, and the diagnosis of post-traumatic stress disorder (PTSD) among refugee groups from Southeast Asia and Central America. PTSD occurs with depressive disorders, and its prevalence rates vary in populations of trauma victims. E. Horwath and M.M. Weissman analyze epidemiological data on anxiety based on DSM-III and DSM-III-R criteria, comparing prevalence rates from the United States with data from other countries. The lifetime prevalence rates of panic disorder are remarkably consistent across community studies and ethnic boundaries. Data on agoraphobia show more variation across studies and cross-culturally.

The chapters in the second part of the book are organized around common themes. These include a description of the culture of the group, its view of mental illness and anxiety, treatment expectations, the possibilities of a therapeutic alliance and family involvement. E. Salman and colleagues examine anxiety disorders of Hispanic-Americans. The authors analyze the culturally bound syndrome of “ataque de nervios,” which is a folk label for loss of control, often with anxiety. The authors stress the need to reconcile the folk diagnoses with the DSM-IV framework.

S.-A. Gopaul-McNicol and J. Brice-Baker compare indigenous and western treatments of anxiety disorders in the Caribbean. G.Y. Iwamasa analyzes demographic and clinical variables in Asian-Americans, who tend to underuse both outpatient and inpatient mental health services. The author points out that, in many Asian ethnic groups, the needs of the family take precedence over those of the individual, that and religion and spirituality are important in everyday family life. CM. Paradis and her colleagues focus on the cognitive-behavioural treatment of anxiety disorders and emotional problems of Orthodox Jews, a minority in their own community. Confidentiality is important in this culture, and mental illness often has to be concealed. The assessment and treatment of patients with strong religious beliefs remain a mental health challenge.

There is still limited information on anxiety disorders in African-Americans. A.M. Neal-Barnett and J. Smith argue that the African-Americans have been targets of misdiagnosis. The authors discuss the clinical importance of spirituality, of the extended family and the therapeutic alliance in the treatment. R. Viswanathan and colleagues stress the fact that some attitudes of patients from the Indian subcontinent tend to be sociocentric rather than egocentric. Family and neighbours are valued, gender and hierarchical roles are rule-bound, and behaviour is influenced by the concept of shame.

In the third part of the volume, I.M. Lesser and colleagues provide a valuable overview of the clinical research on psychopharmacology and ethnicity, mechanism of drug effects and response to treatment. The authors highlight the interplay of ethnic background and genetics, but many of the important variables and relations need more research. In his closing chapter, L.J. Kirmayer reflects on the role of culture in emotional experience, considering the variations of anxiety symptoms in an increasingly ethnically diverse society.

The authors offer an updated and deep insight into factors inherent in the development, manifestation and treatment of anxiety in subjects from different cultures and ethnic groups. The book is well structured and clearly written, though the anxietynculture relations are complex and the evidence is still fragmented. This useful book will interest students and scholars in transcultural psychiatry/psychology and mental health professionals working with patients from ethnic groups.

Answer. I sympathize with your situation. From your description, your husband either has an extremely severe form of panic disorder or a very dependent and “clingy” way of dealing with his anxiety – or a combination of the two scenarios. I think it is important that you discuss the situation with his psychiatrist. Someone having 3-4 panic attacks per hour despite vigorous treatment is not within the expected level of control for the disorder.

You don’t say what medication he’s taking, but I would certainly take another look at them. If his psychiatrist isn’t willing to do so, I would obtain a second opinion from an expert in panic disorder (PD). Start by seeking a referral from a medical school-based department of psychiatry.

Secondly, you don’t say if your husband has received cognitive-behavioral therapy (CBT). I believe this is an essential part of managing severe panic disorder, and would urge you to explore this with the psychiatrist. Do not accept general forms of relaxation therapy or supportive therapy – the therapist must be an expert in cognitive-behavioral therapy. A good behavioral psychologist would be my first pick.

If your insurance would cover it, your husband might benefit from some sort of day program. It doesn’t sound like sitting around at home is a good idea for him. Frankly, if he has spoken of suicide recently, I would take that very seriously, and let his psychiatrist know. He should NOT be “home alone” if he is strongly suicidal. When you got to work, I’d recommend that you arrange in advance a number of times in the day when you will call him. I would advise against responding to non-scheduled calls from him – to do so will only reinforce his neediness.

On the other hand, it is neither wise nor appropriate to punish a cry for help (from someone who is suicidally depressed) by ignoring it – so if this is really the case, your husband shouldn’t be at home alone. You may want to contact the Anxiety Disorders Association of America for more information about panic disorder, or call the Panic Disorder Info Hotline at NIMH. Good luck.

In The American Journal of Psychiatry, Ellen Frank, Ph.D., and colleagues at the University of Pittsburgh School of Medicine released their findings that the same holds true for patients who exhibit panic symptoms belonging to the panic-agoraphobic spectrum.

The researchers looked at a cohort of 61 women, who were subjects in a larger depression study, to determine their treatment outcome, based on how they scored on the Panic-Agoraphobic Spectrum Self-Report scale.

All patients in the larger study were female, ranging in age from 20 to 60, and in at least their second episode of major depression, as determined by DSM-IV. Patients were treated for 12 to 24 weeks to achieve remission of the current depressive episode. Patients were first treated with interpersonal psychotherapy until remission. If they were not responsive to psychotherapy alone, fluoxetine (Prozac) 10 mg/day to 20 mg/day was added to the treatment regimen. Patients who did not meet remission criteria after 24 weeks, or who deteriorated or relapsed, were removed from the study and offered other standard pharmacotherapy treatments.

Within this larger group, 61 women were given the Panic-Agoraphobic Spectrum Self-Report to assess their lifetime history of panic-agoraphobic spectrum symptoms. A score of 35 or higher was used to characterize patients as having clinically significant panic-agoraphobic symptoms. A chi-square test was used to compare the proportion of high- to low-scorers who responded to interpersonal psychotherapy alone. Next, the median time to remission (defined as a Hamilton Depression [HAM-D] Scale rating of 7 or lower during the first of three consecutive weeks) was compared for patients above and below the cut-off score.

Of the 61 patients, 23 (37.7%) were classified as high-scorers. As expected, more of these patients reported a lifetime history of panic disorder than did those who scored below the threshold. Only two (5.3%) of the 38 women who scored below 35 reported a lifetime history of panic or agoraphobia, as compared to nine (39.1%) who had high scores.

As predicted, women who had low scores responded better to psychotherapy (26 of 38, 68.4%) than those with high scores (10 of 23, 43.5%). In addition, high scorers were more likely to need pharmacologic treatment and had a longer median time to remission than low scorers (18.1 weeks versus 10.3 weeks, respectively).

The authors acknowledged several weaknesses in their study. First, only women were studied. Second, assessment with the Panic-Agoraphobic Spectrum Self-Report was only done at one point in the study, rather than longitudinally. Third, the sample size did not lend itself to separate analyses of time to remission for the psychotherapy group and the pharmacology group.

Nevertheless, the investigators summarized, “High levels of panic-agoraphobic spectrum symptoms over the lifetime are associated with a delayed response to treatment whether or not fluoxetine is added to the patient’s treatment regimen”.

Most recently, the selective serotonin reuptake inhibitors (SSRIs) have provided an alternative to the older pharmacologic treatments. Although paroxetine and, very recently, sertraline have FDA-approved indications for the treatment of panic disorder, a significant body of literature exists, as well, for fluvoxamine and, to a lesser extent, fluoxetine. Sheehan and Harnett-Sheehan have comprehensively reviewed the role of SSRIs and Jefferson has reviewed the antidepressants in general in the treatment of panic disorder. As a group, these agents are significantly different from the tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines. They demonstrate little or no abuse potential, orthostatic hypotension, anticholinergic side effects, sedation, or ability to produce hypertension secondary to drug-drug and drug-food interactions. On the whole, they display a profile of CNS-stimulating side effects (e.g., anxiety, insomnia, headaches, nausea, weight loss). Among the serotonin reuptake inhibitors, fluoxetine is the most stimulating and fluvoxamine the least. In addition, paroxetine appears to have some mild anticholinergic properties, and they differ from one another with respect to the drug-drug interactions in which they are involved via P450 isoenzymes. Half-lives of elimination of the parent compounds and their active metabolites constitute another important difference among the four (see Table 2). All four of the SSRIs have been studied in panic disorder with the greatest number of published reports involving fluvoxamine, the largest number of patients treated with paroxetine, and the least number of published reports involving fluoxetine and sertraline.

• Fluoxetine: Based on a total of 195 patients in three open-label studies and one double-blind comparison with desipramine, fluoxetine (10-80 mg/day) has shown some efficacy in the treatment of panic disorder. However, patients appear to be very sensitive to its activating effects, resulting in high dropout rates. Starting doses as low as 2.5 mg/day may be necessary for successful treatment of patients; employing this approach, Schneier et al. reported that 76% of 25 patients with panic disorder markedly improved.

• Fluvoxamine: In multiple double-blind studies, involving over 1,000 patients, fluvoxamine has been shown to be more effective than placebo, maprotiline, and ritanserin (not available in the U.S.) and equal in efficacy to clomipramine and imipramine in the treatment of panic disorder. In one such study, lasting 8 weeks, Black et al. compared fluvoxamine (up to 300 mg/day), cognitive behavior therapy, and placebo in 75 patients. At week 4, 57% of patients taking fluvoxamine, 40% receiving cognitive therapy, and 22% of those taking placebo showed at least moderate improvement. At week 8, 81% of the fluvoxamine group, 53% of the cognitive therapy group, and 29% of the placebo group were free of panic attacks; the difference between the fluvoxamine and placebo groups was statistically significant.

• Sertraline: Sertraline (50, 100, and 200 mg/day fixed doses), in a 12-week, multicenter, placebo-controlled study of 320 patients with panic disorder, significantly reduced the number of panic attacks at the 100 and 200 mg/day doses. Of concern, 22% of patients receiving sertraline discontinued treatment secondary to adverse effects, while there were no dropouts in the placebo group.

• Paroxetine: The efficacy of paroxetine in the treatment of panic disorder has been studied in over 1,200 patients and reported in three published studies and three presentations. All of these trials were double-blind and placebo-controlled, and overall, paroxetine (40-60 mg/day) was found to be superior to placebo and equal to either clomipramine (150 mg/day) or alprazolam (6 mg/day). Onset of action can be slow, however, with a 50% reduction in panic attacks not occurring until week 6 and a reduction to one or zero attacks lasting three consecutive weeks not occurring until week 12. In a 10-week, fixed-dose (10, 20, and 40 mg/day) study of 278 patients, significant differences from placebo were seen only in the patients treated with 40 mg/day.

Conclusions

Currently available data indicate that the serotonin reuptake inhibitors are emerging as distinct options in the treatment of panic disorder. As with the older treatments, onset of action can be slow, effective doses are similar to those needed in treating major depression, and, at times, drug discontinuation secondary to adverse effects can be a significant problem. Overall, however, the SSRIs have a number of advantages over the older options, particularly with respect to adverse effects and abuse and dependence potential, and are already viewed by many prescribers as first-line agents, especially in patients with panic disorder and concomitant major depression. Further information on long-term efficacy as well as comparisons of each of the serotonin reuptake inhibitors with the others would be helpful in fully assessing their place in the treatment of panic disorder.

Epidemiology and Clinical Features

Panic disorder is one of the primary anxiety disorders described in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association. It is a chronic disorder with a lifetime prevalence estimated to be between 1.5% and 3.5% and an onset generally in early adulthood. It is characterized by the occurrence of recurrent, unexpected panic attacks followed by at least one month of persistent concern about experiencing further attacks, worry about the consequences of the attacks, or a significant change in behavior secondary to the attacks. The attacks may last seconds to minutes and are characterized by dyspnea, palpitations, tremulousness, dizziness, hot and cold flashes, diaphoresis, chest pain, feelings of unreality, numbness or tingling, faintness, fear of going crazy, and fear of dying (see Table 1). These attacks are extremely frightening and disabling; many of these patients are seen in the medical emergency room because they think they are having a heart attack. If a sufficient number of panic attacks occur, patients may develop anticipatory anxiety (i.e., anxiety associated with the fear of the next occurrence) as well as avoidant behavior. When this avoidant behavior severely restricts the daily activity of the individual (i.e., avoiding public places and/or leaving home for fear of having a panic attack during which help will not be available), the diagnosis of panic disorder with agoraphobia is made. Up to 70% of patients with panic disorder fulfill the diagnostic criteria for major depression at some point in their lives.

Traditional Treatments

Until recently, primarily three drugs have been used in the pharmacotherapy of panic disorder: the tricyclic antidepressant imipramine; the monoamine oxidase inhibitor phenelzine; and the benzodiazepine alprazolam. Among the three, only alprazolam has an FDA approved indication for the treatment of panic disorder; however, all three have demonstrated efficacy. Often, imipramine would be selected for patients with concomitant depression and avoided in patients who could not tolerate the sedative, anticholinergic, hypotensive, or cardiac conduction adverse effects. Phenelzine may have an advantage in patients with significant phobic avoidance; however, it is commonly reserved as a last resort due to fear over drug-drug and drug-food interactions resulting in possible hypertensive crises. Alprazolam would be given to patients with significant anticipatory anxiety, as well as those who could not tolerate imipramine, and avoided in patients who would be adversely affected by the drug’s tendency to produce sedation and psychomotor impairment. In addition, most prescribers would avoid use of this agent in any patients with a history of alcohol or substance abuse due to its abuse potential. More recently, clonazepam was approved by the FDA for the treatment of panic disorder. Compared with alprazolam, it has the advantage of a longer half-life of elimination, reducing the frequency of dosing as well as the inter-dose rebound anxiety sometimes seen with alprazolam.

Five leading mental disorders affect 10 million Americans, but many people, especially those suffering from depression and panic disorder, do not seek help. It is estimated that during any one year, almost 18 million American adults will suffer from a depressive illness. Among people 65 years of age and older, an estimated 3% suffer from clinical depression.

Five Major Disorders

There are five major mental disorders.

Schizophrenia is a chronic disabling illness. About 100,000 patients with schizophrenia are in public mental hospitals. Schizophrenia affects men and women equally, but onset is earlier in men. The first psychotic symptoms are often seen in the teens or early 20s. Onset past the age of 40 is rare. A schizophrenic person may appear quite normal much of the time. Schizophrenia is not “split personality,” which is an entirely different, and rare, disorder. The children of a parent with schizophrenia will have a 10% chance of developing the condition.

Depression, the most prevalent mental disorder, is divided among a number of clinical conditions, ranging from transient depression to clinical depression, or depression that lasts for months on end. Two serious types of clinical depression are major and bipolar depression. Major depression frequently presents in one’s lifetime as one or more depressive episodes. First depressive disorders generally appear in one’s mid-20s. Major depression is more common in women, but in
children strikes boys and girls equally.

Bipolar disorder, also known as manic depression, is characterized by mood swings and affects two million Americans at any given time. The disorder usually manifests in one’s early 20s.

Obsessive-compulsive disorder (OCD) is one of the anxiety disorders, and affects males and females equally.

Panic disorders affect more people than is realized because many sufferers do not seek help. A combination of drugs and psychotherapy is effective in alleviating this disorder.