Panic disorder: effective treatment options

Author: S. Atezaz Saeed, Timothy J. Bruce
Date: May 15, 1998

Panic disorder is an anxiety disorder characterized by unexpected panic attacks. It is often associated with situational (agoraphobic) avoidance stemming from fear of further attacks.[1] Epidemiologic studies suggest that panic disorder, with or without agoraphobia, has a lifetime prevalence between 1.5 and 3.0 percent[1] and a familial tendency. It can run a chronic, relapsing course and can produce significant disability and personal distress. Panic disorder is commonly seen in the family practice setting, but it often eludes detection or is misdiagnosed because its clinical presentation mimics that of other medical conditions.[2] A large body of evidence shows that panic disorder responds to various pharmacotherapies and to cognitive and cognitive-behavioral therapies. Early recognition and prompt, appropriate treatment are the keys to managing this disorder effectively.

Identifying Panic Disorder With and Without Agoraphobia

Panic disorder is characterized by the unexpected, "out of the blue" panic attack. A panic attack is defined as a discrete episode of intense symptoms that peak within 10 minutes and primarily involve sympathetic nervous system manifestations. According to criteria given in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV),[1] a panic attack must include at least four of the symptoms listed in Table 1.

TABLE 1 Symptoms of Panic Attacks

Neurologic symptoms

Dizzy, light-headed or unsteady feeling



Fainting Cardiac symptoms

Chest pain or discomfort

Palpitations, heart pounding or tachycardia

Sweating Respiratory symptoms

Shortness of breath

Feeling of smothering or choking Gastrointestinal symptoms


Abdominal distress Psychologic symptoms


Fear of losing control, going crazy or dying Miscellaneous symptoms

Chills or hot flushes

A diagnosis of panic disorder is made if the patient has experienced recurrent, unexpected panic attacks and shows at least one of the following characteristics: (1) persistent concern about having another attack (anticipatory anxiety); (2) worry about the implications of an attack or its consequences (e.g., suffering a catastrophic medical or mental consequence), or (3) a significant change in behavior related to the attacks.

In clinical populations, panic disorder is usually accompanied by agoraphobia. Agoraphobia refers to avoidance behavior motivated by fear of having another panic attack. It may involve activities that patients fear could provoke an attack, situations where escape may not be readily available or routine activities during which patients are not accompanied by a "safe person" whom they believe could help in case of an attack. Table 2 lists common types of agoraphobic fear and avoidance.

TABLE 2 Examples of Activities And Situations that May be Avoided by Patients with Agophobia

Being far away from home Being without the company of a "safe" person Physical exertion that patients believe could provoke a panic

attack Going to places where escape is not readily available (e.g.,

restaurants, theaters, stores, public transportation) Driving Places where embarrassment could be a consequence of suffering

a panic attack (e.g., social gatherings) Ingesting substances that patients believe could provoke panic

(e.g., foods, medicines, alcohol, caffeine)

Clinical Management of Panic Disorder

Patients presenting with panic-like symptoms should receive a thorough initial evaluation that goes beyond assessment of their primary somatic complaints. Areas of initial evaluation are outlined in Table 3. Several authors[3,4] have recommended a specific work-up for these patients to reduce unnecessary assessments. Panic disorder can be treated effectively with pharmacotherapy, cognitive and cognitive-behavioral therapies or a combination of therapies.

TABLE 3 Areas of Evaluation for Patients with Panic Symptoms

Criteria for an unexpected panic attack Agoraphobic avoidance Use of caffeine and other anxiety-provoking substances Substance-use history Medical history to eliminate organic etiology Psychiatric comorbidity (e.g., depression, interpersonal conflicts) Previous assessments and treatments (psychiatric, medical) Family history

The National Institutes of Health Consensus Development Conference on Treatment of Panic Disorder[5] recommends that patients who are diagnosed with panic disorder should be,provided with a description of indicated treatment options and the advantages and disadvantages of each option. Treatment selection should then be made with the patient's input and in consideration of the severity of the presenting complaints, and the patient's specific history and preferences. The following sections outline treatment options for patients with panic disorder and their known advantages and disadvantages. Considerations for selecting treatment also are presented.

Drug Therapy

Table 4 lists pharmacologic agents used to treat panic disorder and their common therapeutic dosage ranges.

TABLE 4 Drugs Used For Treating Panic Disorder

Drug Dosage rangeTricyclic antidepressants Imipramine (Tofranil) 50 to 300 mg per day Clomipramine (Anafranil) 25 to 250 mg per day Nortriptyline (Pamelor) 25 to 100 mg per day Desipramine (Norpramin) 25 to 300 mg per daySRIs Fluoxetine (Prozac) 20 to 80 mg per day Paroxetine (Paxil) 10 to 50 mg per day Sertraline (Zoloft) 50 to 200 mg per day Fluvoxamine (Luvox) 50 to 300 mg per dayMAOIs Phenelzine (Nardil) 45 to 90 mg per day Tranylcypromine (Parnate) 30 to 60 mg per dayBenzodiazepines Alprazolam (Xanax) 2 to 10 mg per day Lorazepam (Ativan) 2 to 6 mg per day Clonazepam (Klonopin) 1 to 3 mg per day

SSRIs = selective serotonin reuptake inhibitors; MAOIs = monoamine oxidase inhibitors,

Tricyclic Antidepressants

Imipramine (Tofranil) is the medication for panic disorder that has been most thoroughly studied, with at least 10 double-blind, placebo-controlled studies supporting its efficacy in the acute treatment of panic disorder.[6] Clomipramine (Anafranil) has shown similar results in several double-blind trials as well. Other tricyclic antidepressants that have shown promise are listed in Table 4.

The onset of therapeutic action for tricyclic antidepressants typically takes three to four weeks. The average length of treatment is approximately six months but depends on several factors, including the efficiency with which panic suppression is achieved and agoraphobic avoidance, if any, is overcome. In obtaining an optimal response, the physician may find it helpful to assess plasma levels. For example, a therapeutic response should be evident at a level greater than 150 mg per ml, (imipramine and desipramine [Norpramin] combined) in patients receiving imipramine.

Approximately one fourth of patients cannot tolerate the side effects of tricyclic antidepressants. Side effects are commonly anticholinergic (constipation, dry mouth, blurred vision and urinary retention), histaminergic (sedation and weight gain) or adrenergic (orthostatic hypotension).

One of the most burdensome adverse effects for patients with panic disorder, who often fear their own bodily sensations, is the "activation syndrome" that occurs on initial titration in approximately 25 to 40 percent of patients. The syndrome often can be mitigated by education, reassurances and initiating a low starting dosage (e.g., 10 mg of imipramine per day), then increasing gradually and flexibly at a rate of approximately 10 mg every two to three days until a dosage of 50 to 75 mg is achieved. An increment of 25 mg every two to four days from that point is usually well tolerated.

Since patients with panic disorder are often very sensitive to side effect symptoms, they may need more reassurance throughout pharmacotherapy than other patients. Physicians should also be aware that a withdrawal syndrome following abrupt cessation of these agents has been described.[7]

Imipramine and clornipramine are considered first-line treatment options for panic disorder. Some advantages and disadvantages of these agents are listed in Table 5.

TABLE 5 Selected Advantages and Disadvantages of Major Treatment Modalities in Patients with Panic Disorder

Acute relapse is common when pharmacotherapy for panic disorder is discontinued.[35] Since recent studies have shown that cognitive-behavioral therapy can effectively reduce discontinuation and relapse difficulties associated with the discontinuation of pharmacotherapy, its adjunctive use with any pharmacotherapy should be considered to help reduce these risks. Other considerations for selecting a first-line treatment include the patient's preference for an approach that includes medication versus one that does not, as well as the availability of cognitive-behavioral treatment in the community.

Once treatment is selected, patients should be monitored periodically. When stabilized, patients should be encouraged to reenter previously avoided situations gradually, regardless of the treatment approach being used. If the treatment response is inadequate after approximately eight weeks of therapy, alternatives should be reconsidered.

Finally, patients with panic disorder often need sensitive clinical management. Many of these patients have been ill for several years and tend to have a history of varied, ineffective and failed treatments. Establishing a therapeutic alliance with patients, as described in Table 8, is an important aspect of any treatment selected.

TABLE 8 Establishing a Therapeutic Alliance in the Treatment of Patients with Panic Disorders

Establish a therapeutic relationship by providing the

following: respectful attention to patient's concerns,

realistic reassurance and instillation of hope, and a

willingness to be available in case of unexpected problems. Provide the patient with some knowledge about panic

disorder (e.g., it is common, it is not life-threatening, it

is treatable). Discuss the components of panic disorder (panic attacks,

anticipatory anxiety and avoidance) and how treatment targets

changes in each component. Explore and discuss patient's concerns about medications. Explain treatment options and their advantages and disadvantages.


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S. ATEZAZ SAEED, M.D., is acting chairman of the Department of Psychiatry and Behavioral Medicine and director of education in psychiatry at the University of Illinois College of Medicine at Peoria. He is also co-director of the Anxiety and Mood Disorders Clinic of the university. Dr. Saeed is a graduate of Dow Medical College, Karachi, Pakistan, and completed a residency in psychiatry at the Illinois State Psychiatric Institute, Chicago.

TIMOTHY J. BRUCE, PH.D., is assistant professor of psychology and director of undergraduate medical education at the University of Illinois College of Medicine at Peoria. He also is co-director of the Anxiety and Mood Disorders Clinic of the university. Dr. Bruce is a graduate of the State University of New York at Albany and completed a residency in clinical psychology at Wilford Hall USAF Medical Center, San Antonio, Tex.

Address correspondence to S. Atezaz Saeed, M.D., Acting Chairman, Department of Psychology and Behavioral Medicine, University of Illinois College of Medicine at Peoria, 7725 N. Knoxville Ave., Lower Level, Peoria, IL 61614. Reprints are not available from the authors.

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