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Murray B. Stein, Laura Campbell-Sills: Chapter 29. Panic Disorder, in Gabbard’s Treatments of Psychiatric Disorders, 4th

Edition. Edited by Glen O. Gabbard. Copyright ©2009 American Psychiatric Publishing, Inc. DOI:

10.1176/appi.books.9781585622986.258062. Printed 5/10/2009 from www.psychiatryonline.com

Gabbard’s Treatments of Psychiatric Disorders > Part VI. Anxiety Disorders, Dissociative Disorders, and Adjustment

Disorders >

Chapter 29. Panic Disorder

INTRODUCTION

In this chapter we review current treatments for panic disorder with or without agoraphobia. The

first section covers pharmacotherapeutic approaches, and the second section covers

psychotherapeutic approaches and discusses combining these strategies. The treatment

recommendations stem from a combination of practice guidelines (e.g., American Psychiatric

Association Work Group on Panic Disorder 1998; Bandelow et al. 2002), the published scientific

literature, and the authors’ clinical experience. For the most part, we will reference seminal reports

stemming from double-blind, randomized controlled trials (RCTs) and authoritative review papers

and will limit citing of uncontrolled case reports or open-label treatment series to areas (e.g.,

psychodynamic psychotherapy) where no other literature exists. We will also avoid providing

specific dosing recommendations for particular drugs, as this information is better obtained from

other sources that are frequently updated (e.g., manufacturers’ Web sites). We will not discuss the

treatment of panic disorder in special populations (e.g., older adults, children, pregnant women),

thereby acknowledging that these topics require additional consideration that cannot be

accomplished in the space allotted to us.

Panic disorder is a syndrome characterized by recurrent panic attacks that occur, at least early in

the illness, unexpectedly and are followed by persistent concern, worry, or change in behavior in

relation to the attacks. In many cases, the change in behavior involves avoidance of places or

activities that the individual believes will be difficult to escape from if panic attacks were to occur.

When the avoidance is extensive (e.g., the individual will not leave home or will only drive the car

on quiet streets near home) or requires substantial accommodations to function (e.g., the

individual will only leave home if accompanied by a trusted friend or spouse), then the individual is

said to suffer from panic disorder with agoraphobia. Agoraphobia can also occur in the absence of a

history of panic disorder (Bienvenu et al. 2006), presumably through other etiological pathways,

but its treatment will not be discussed here.

The 12-month general population prevalence of panic disorder (with or without agoraphobia) in the

United States is 2.7% (Kessler et al. 2005b). Lifetime prevalence of panic disorder (with or without

agoraphobia) is 4.7% (Kessler et al. 2005a). In addition to being common, panic disorder is a very

impairing illness, associated with substantial reductions in functioning and health-related quality of

life (Markowitz et al. 1989; Mendlowicz and Stein 2000; Rapaport et al. 2005; Sherbourne et al.

1996; Stein et al. 2005). For all of these reasons, panic disorder is increasingly being recognized as

a serious public health problem, and efforts directed at its treatment have galvanized therapeutic

momentum for all of the anxiety disorders.

PHARMACOLOGICAL TREATMENTS FOR PANIC DISORDER

Donald Klein’s (1964) observation that the tricyclic antidepressant (TCA) imipramine blocked panic

attacks in hospitalized patients ushered in the era of psychopharmacological treatments for panic

disorder. It has subsequently been shown that several (but not all) classes of antidepressants are

effective in the treatment of panic disorder, as are certain benzodiazepines. No other class of

medication has better than equivocal evidence of efficacy, although some promising novel agents

are in development. We will begin with a review of the various types of antidepressants with known

antipanic efficacy, continue with a review of the benzodiazepines, and end this section of the

chapter with a brief appraisal of novel antipanic agents.Print: Chapter 29. Panic Disorder

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Pharmacotherapy for panic disorder assumes a model wherein panic attacks can be prevented from

occurring using pharmacological means. But the pharmacological treatment of panic disorder is

aimed not only at reducing or eliminating panic attacks but also at reducing avoidance behavior,

anticipatory anxiety, and comorbid conditions such as major depression or other anxiety disorders

(Pollack 2005). Although the neurobiology of panic disorder is far from being completely

understood, incremental advances in functional neuroimaging—such as positron emission

tomography studies with serotonin receptor subtype–specific ligands (Neumeister et al. 2004) and

magnetic resonance spectroscopy studies measuring gamma-aminobutyric acid (GABA) levels in the

central nervous system (Goddard et al. 2004)—are consonant with clinical observations that

manipulations in brain serotonergic and/or GABA systems underlie the effects of most available

panic disorder pharmacotherapies.

Individual differences in response to pharmacological treatments for panic disorder are poorly

understood, and the current state of the art requires individualized therapeutic trials to find the

appropriate therapeutic agent and dose for a given patient. Most experts recommend starting with

an antidepressant (usually a selective serotonin reuptake inhibitor [SSRI]) rather than a

benzodiazepine, as the former has no potential for abuse and will also treat depression, which is so

often comorbid with panic disorder. Antidepressants can take 3–4 weeks to exhibit their

therapeutic effects in panic disorder; benzodiazepines, on the other hand, can have immediate

beneficial effects. It should be noted that most of the pharmacological RCTs in panic disorder have

been of relatively short duration (e.g., 12 weeks), making it difficult to extrapolate to make

recommendations about optimal duration of treatment. The recommendation is often made,

however, to continue medication management for 9–12 months and then to discuss with the patient

the possibility of a slow taper over several weeks to months. The possibility that the provision of

certain psychological therapies might prevent relapse for panic disorder is discussed later in this

chapter (see section titled “Use of Cognitive-Behavioral Therapy to Aid in Medication

Discontinuation”).

Antidepressants

Selective Serotonin Reuptake Inhibitors

Several dozen RCTs support the efficacy of the SSRIs for panic disorder. The American Psychiatric

Association Practice Guidelines for Panic Disorder recommend the SSRIs as the preferred

pharmacological treatment (American Psychiatric Association Work Group on Panic Disorder 1998)

based on their record of superior tolerability and safety compared to older antipanic agents such as

the TCAs. Paroxetine was the first SSRI approved by the U.S. Food and Drug Administration (FDA)

for the treatment of panic disorder, and there are numerous RCTs demonstrating its safety and

utility (Ballenger et al. 1998; Pollack and Doyle 2003), including that of the more recently approved

controlled-release version of paroxetine (Sheehan et al. 2005). Sertraline, another SSRI approved

by the FDA for the treatment of panic disorder, also has a large body of evidence demonstrating its

safety and utility (Londborg et al. 1998; Pohl et al. 1998; Pollack et al. 1998) and its proven

noninferiority to (i.e., it is at least as efficacious as) paroxetine (Bandelow et al. 2004). Other

SSRIs, including fluoxetine (FDA approved) (Michelson et al. 2001), fluvoxamine (Asnis et al.

2001), and citalopram (Wade et al. 1997) and its s enantiomer escitalopram (Stahl et al. 2003),

have one or more published RCTs showing their efficacy and safety in the treatment of panic

disorder.

Although some SSRIs have FDA approval for panic disorder and others do not, it is our opinion that

all drugs in this class are equally effective in the treatment of panic disorder. For patients with prior

SSRI treatment histories, the particular SSRI that proved beneficial in the past would usually be the

one to start with. A history of difficulty with particular side effects may also be taken into

consideration in choosing SSRIs with particular tolerability profiles, although most adverse events

are so idiosyncratic that trying to predict match of patient and side-effect profile may be a futile

exercise. Cost may enter into the decision: Formulary restrictions may guide the choice of SSRI in

some health care systems. Given that several of the SSRIs are now available in generic form,Print: Chapter 29. Panic Disorder

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consideration should be given to using them preferentially.

Other Antidepressants

Of the “dual” (serotonin and norepinephrine) reuptake inhibitors, venlafaxine ER at doses of

75–225 mg was found to be effective in treating panic disorder (Bradwejn et al. 2005) and recently

obtained FDA approval for this indication. Duloxetine is sufficiently new to the market that its use

for this purpose has yet to be determined.

Other atypical antidepressants such as mirtazapine (Ribeiro et al. 2001) and trazodone are of

unproven efficacy in the treatment of panic disorder. Bupropion was notably ineffective in one RCT

in patients with panic disorder (Sheehan et al. 1990). Reversible inhibitors of monoamine oxidase

type A (RIMAs), such as moclobemide, are of equivocal efficacy in the treatment of panic disorder

(Loerch et al. 1999) and are not currently available in the United States.

Imipramine, which started the pharmacology revolution in panic disorder, and some other TCAs and

heterocyclic antidepressants (e.g., desipramine, clomipramine) are efficacious in the treatment of

panic disorder. Until the arrival of the SSRIs in the mid-1980s, these and the benzodiazepines were

the only established pharmacological therapies for panic disorder, but their widespread use was

limited by the frequent occurrence of adverse events (e.g., tachycardia, jitteriness) to which

patients with panic disorder seemed particularly sensitive. Monoamine oxidase inhibitors (MAOIs)

have even more limited data supporting their efficacy in panic disorder, and their side-effect burden

and the need for patients to adhere to a special diet further limit their use. For these reasons, TCAs

and MAOIs are seldom used nowadays. They may be considered as an option for patients who are

resistant to other therapies—although their use in this context is unproven.

Benzodiazepines

Benzodiazepines are unequivocally effective in the treatment of panic disorder, although their use

is limited by concerns about potential for abuse and dependence and by their more limited

spectrum of efficacy compared to the antidepressants. Practice guidelines remind practitioners to

use benzodiazepines judiciously (e.g., do not prescribe under most circumstances to persons with

known substance abuse histories; monitor risk–benefit ratios for use on a regular basis throughout

treatment) but suggest that undue concerns about tolerance and abuse may be inappropriately

restricting use of this very effective class of medications for panic disorder (American Psychiatric

Association Work Group on Panic Disorder 1998). Even though the SSRIs have been widely touted

(and aggressively promoted by pharmaceutical companies) as the preferred pharmacological

treatment for panic disorder for the past 15 years, many patients in the community continue to

receive treatment with a benzodiazepine (often in combination with an SSRI) (S. E. Bruce et al.

2003). This observation raises the likelihood that patients and practitioners continue to use

benzodiazepines in panic disorder because other available treatments (e.g., antidepressants) fail to

adequately meet their therapeutic needs. Thus, until even more effective and safe alternatives

become available, the prescription of benzodiazepines for some patients with panic disorder will

remain a clinical necessity.

Benzodiazepine Monotherapy

Most RCTs of benzodiazepines have involved the high-potency agents alprazolam or clonazepam.

Both of these medications are safe and effective in the treatment of panic disorder (Pecknold et al.

1994; Rosenbaum et al. 1997), although concerns have been raised about the toxicity of alprazolam

in the case of overdose (Isbister et al. 2004). Alprazolam, which has a shorter duration of action

than clonazepam, may also be more difficult to taper, and withdrawal symptoms may mimic panic

symptoms and therefore complicate discontinuation or dosage reduction. There is no reason to

believe that these two benzodiazepines are unique in their antipanic efficacy, and others (e.g.,

lorazepam) would be expected to work equally well, if given at equipotent doses. As previously

noted, although concern about tolerance to the effects of benzodiazepines is often voiced as an

issue that limits their use, tolerance to the antipanic effects of alprazolam or clonazepam is seldom

encountered (Nagy et al. 1989; Worthington et al. 1998).Print: Chapter 29. Panic Disorder

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Adjunctive Use of Benzodiazepines

As noted earlier in this chapter, benzodiazepines are frequently prescribed for panic disorder in

conjunction with SSRIs. This presumably reflects better symptom control than is obtained with

adjunctive benzodiazepine use, although evidence in the literature for such effects is sparse. One

special better-documented niche for adjunctive benzodiazepines is to accelerate the speed of

response to pharmacotherapy, compared with SSRIs alone—which typically take 3–4 weeks to

achieve their effects, and even longer to achieve full effect. By the time some patients with panic

disorder seek treatment, they may be at the point where their symptoms are compromising their

ability to function (e.g., to function in the workplace or to care for their children) and the luxury of

waiting 3–4 weeks for an SSRI to work is not an option. In such cases, it is possible to administer

an adjunctive benzodiazepine for the first few weeks (with the plan to taper it once the SSRI has

achieved some measure of efficacy) and obtain quicker antipanic effects than if the SSRI is used

alone (Goddard et al. 2001; Pollack et al. 2003).

Other Pharmacotherapeutic Agents

Although a variety of anticonvulsants (including but not limited to valproate, gabapentin, and

levetiracetam) have been proposed as potentially useful in the treatment of panic disorder (and

other anxiety disorders) (Van Ameringen et al. 2004), the only published RCT is a study in which

gabapentin was not found to be superior to placebo (Pande et al. 2000). Thus, a role for

anticonvulsants in the treatment of panic disorder remains to be elucidated.

Beta-adrenergic blocking agents (beta-blockers) have a long history of use in various anxiety

states, but their efficacy in panic disorder is equivocal at best, and their side-effect profile (e.g.,

sleep disturbance, possible worsening of depression, exercise intolerance) even further limits their

utility.

Buspirone, although effective in the treatment of generalized anxiety disorder, is ineffective in the

treatment of panic disorder (Sheehan et al. 1990, 1993).

PSYCHOLOGICAL TREATMENTS FOR PANIC DISORDER

This section reviews nonmedication treatments for panic disorder. One psychological treatment,

cognitive-behavioral therapy (CBT), has been rigorously tested and can be recommended with

confidence as a first-line treatment for panic disorder. We describe the major components of CBT,

review its evidence base, and consider its special applications (e.g., modified forms of CBT for

medication discontinuation). Other psychological treatments, such as panic-focused psychodynamic

psychotherapy and eye movement desensitization and reprocessing (EMDR), have shown some

promising but very preliminary results. These treatments are not recommended as initial

treatments for panic disorder; however, we review them to provide an understanding of their

empirical status and the future work that is needed to establish or disprove their utility.

Cognitive-Behavioral Therapy

CBT is a well-validated and effective treatment for panic disorder. A number of rigorously executed

RCTs support its efficacy (e.g., Barlow et al. 2000; Clark et al. 1994). CBT is effective when

delivered on an individual basis (e.g., Clark et al. 1994) and when presented in a group format

(Telch et al. 1993). During the acute-treatment phase, the effects of CBT are approximately equal

to the effects of first-line pharmacotherapies. However, CBT may be associated with lower rates of

relapse following treatment discontinuation than medication (Barlow et al. 2000). Positive

outcomes resulting from CBT have been shown to persist for up to 2 years following treatment

withdrawal (Craske et al. 1991).

Despite these well-documented benefits, CBT remains an underutilized treatment for panic disorder

(Goisman et al. 1999). Although this underutilization is not completely understood, one likely factor

is incomplete dissemination. Effective medications for panic disorder are highly visible to the public

and professional community through advertising, whereas CBT does not benefit from this type of

promotion. Most individuals with panic disorder have access to a physician, who may prescribePrint: Chapter 29. Panic Disorder

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medication, but fewer have access to mental health professionals. In addition, many mental health

professionals have not received training in empirically validated psychological treatments such as

CBT. In certain settings and geographic regions, there may be a lack of professionals who are

competent to deliver this treatment. Improving dissemination and training efforts will continue to

be an important focus for researchers and clinicians who want to ensure that CBT is a readily

available treatment for individuals suffering from panic disorder (Stirman et al. 2004).

Theoretical Basis of Cognitive-Behavioral Therapy

The cognitive-behavioral conceptualization of panic disorder is based on behavioral theories of fear

conditioning (Bouton et al. 2001) and cognitive theories that highlight the role of anxious thinking

(Clark 1986). More behaviorally oriented CBT models hypothesize that anxiety and panic have

become conditioned reactions to certain internal and external cues. Common internal or

interoceptive cues include changes in heart rate, breathing, and dizziness, whereas common

external or situational cues include driving, enclosed spaces, and public places. When interoceptive

or situational cues have been associated with panic on multiple occasions, they come to reliably

elicit the panic response in a classical conditioning fashion (Bouton et al. 2001). Treatment

therefore must address the learned associations between these situational cues and panic

responses.

Most CBT models also acknowledge a role for anxiety-escalating cognitions in panic disorder. Clark

(1986) notably referred to this type of thinking as “catastrophic misinterpretations of bodily

sensations.” Patients with panic disorder are thought to hold anxious beliefs about the significance

of fluctuations in bodily sensations. Common misinterpretations of sensations associated with panic

attacks include the beliefs that one is having a heart attack, fainting, “going crazy,” or even dying.

When physical sensations are detected, these beliefs may contribute to an escalation of fear that

culminates in a panic attack. Individuals with panic disorder also may be preoccupied with anxious

thoughts about nonphysical consequences of panic symptoms (e.g., social embarrassment).

Consequently, correcting anxious cognitions about physical sensations is considered an integral

part of treatment for panic disorder.

Components of Cognitive-Behavioral Therapy

A number of different forms of CBT for panic disorder have proven efficacious, including Barlow’s

Panic Control Treatment (Barlow et al. 1989) and Clark’s Cognitive Therapy (Clark et al. 1994).

Although specific CBT protocols vary somewhat in their elements and emphases, they share several

core components. These components are psychoeducation, identification and modification of

panic-related cognitions (cognitive restructuring), exposure to feared sensations and situations,

and relapse prevention. Each of these components is reviewed in detail below.

Psychoeducation

Psychoeducation serves several important purposes in CBT including facilitating a strong

therapeutic alliance, providing the patient with a sense of hope and self-efficacy, enhancing

motivation, and beginning to challenge the patient’s fearful cognitions about panic symptoms.

Psychoeducation aids in the development of the therapeutic alliance because it fosters a common

understanding of panic disorder between therapist and patient. This approach translates into a

collaborative working relationship in which therapist and patient work together to help the patient

achieve symptom reduction and life improvement. Describing the cognitive-behavioral

conceptualization of panic disorder also enhances patients’ understanding of why they will be asked

to practice certain skills in therapy. Comprehension of why certain exercises are necessary to break

the cycle of panic may increase compliance with the more challenging phases of treatment.

Educating the patient about the possible causes and maintaining factors of panic disorder also lays

the groundwork for challenging anxious cognitions that contribute to the disorder. Many patients

enter therapy with beliefs that panic symptoms are dangerous and may lead to disastrous outcomes

such as fainting, having a heart attack, “going crazy,” or dying. The CBT therapist provides

corrective information centered on the idea that the symptoms of panic disorder result from aPrint: Chapter 29. Panic Disorder

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harmless (albeit uncomfortable) misfiring of the body’s “fight-or-flight” system. This new

information provides a radically different interpretation of panic symptoms for some

patients—namely, that panic symptoms are part of a reaction that is intended to protect the

organism in dangerous situations. This information alone may help some patients reinterpret their

symptoms in a less anxiety-provoking manner, leading to less severe and less frequent panic

attacks.

Finally, the psychoeducational component of CBT addresses the role of avoidance in maintaining

fear. Patients learn that avoidance (of sensations or situations) sends a message of danger and

prevents the natural process of habituation from occurring. CBT therapists emphasize the negative

effects of avoidance early and often, because doing so provides a rationale and may enhance

motivation for the exposure phase of treatment.

Cognitive Restructuring

Patients with panic disorder endorse a wide range of anxious cognitions focused on physical

catastrophes, loss of control, negative social evaluation, and inability to maintain role functioning

due to panic (Raffa et al. 2004). Most forms of CBT for panic disorder include a systematic approach

for altering these anxious thoughts called “cognitive restructuring.” The first step of cognitive

restructuring is to identify the anxious thoughts that contribute to panic disorder. This may seem

simple and obvious; however, sometimes patients’ anxious cognitions have become so automatic

that they barely recognize what they are thinking during panic episodes. Keeping records or diaries

of anxious thoughts can help patients pay more attention to the cognitive processes that contribute

to anxiety.

Once patients are adept at identifying thoughts that contribute to panic episodes, they learn about

common errors in thinking that frequently accompany anxiety, which are sometimes called

“cognitive distortions.” For example, individuals who are experiencing anxiety often overestimate

the probability of negative events (“probability overestimation”) and underestimate their ability to

cope with feared outcomes (“catastrophizing”). This combination of negative thought patterns

contributes to an overall feeling of helplessness and dread (e.g., “Something terrible is going to

happen and I won’t be able to handle it”). In CBT, patients learn to recognize cognitive distortions

in their own thinking. They are subsequently taught to question their anxious assumptions and

generate more realistic and less anxiety-provoking alternatives.

Practicing cognitive restructuring allows patients to develop thinking patterns that increase their

comfort level and their self-confidence. For example, a patient who initially feared causing a car

accident due to panic symptoms might practice thinking, “Even though I feel out of control during

panic attacks, I am actually completely in control of my driving. I have been able to successfully

control my car numerous times while having panic symptoms, and not once have I caused a wreck.

Panic symptoms may be uncomfortable, but they do not cause car accidents.” The new belief

focuses on the objective evidence for the feared outcome (e.g., no car accidents despite numerous

instances of panic symptoms while driving) and the patient’s ability to cope (e.g., the ability to

control the car and to deal with discomfort). Patients typically need to repeat cognitive

restructuring exercises many times before this type of adaptive nonanxious thinking can compete

with the previously held anxious beliefs.

Patients with panic disorder also may challenge their anxious beliefs by carrying out “behavioral

experiments.” In these exercises, individuals first identify feared outcomes of a commonly avoided

situation (e.g., “If I drink coffee, my heart will race so quickly that I will need to go to the

hospital”). Patients then confront the situation with the aim of collecting “data” that will either

support or challenge their anxious predictions. When patients compare the actual outcomes to their

fearful predictions, they usually find that their fears were unfounded. In this way, therefore,

behavioral experiments can undermine anxious beliefs and strengthen the more rational thinking

that is promoted in therapy.

Interoceptive and Situational ExposurePrint: Chapter 29. Panic Disorder

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Exposure is considered one of the most powerful and challenging aspects of CBT for anxiety

disorders. In the case of panic disorder, exposure interventions typically focus on physical

sensations and external situations that commonly provoke panic.

Interoceptive conditioning is the process by which an internal cue becomes associated with a fear

reaction. Patients with panic disorder are thought to develop conditioned fear reactions to some

benign physical symptoms such as heart racing or dizziness (e.g., Bouton et al. 2001).

Interoceptive exposure entails deliberately eliciting physical symptoms in a repeated fashion in

order to break the association between the symptoms and the fear reaction. The level of fear of

various physical symptoms is first assessed through a series of exercises designed to bring on

different sensations (e.g., breathing through a straw for breathlessness, spinning in a chair for

dizziness). Patients often report very high levels of fear when they first attempt these exercises.

The therapist assigns repeated practice of each feared exercise until the patient can experience the

physical symptoms without significant fear. Interoceptive exposure is a central component of many

CBT protocols, because it targets the “core” of panic disorder—the fear of physical sensations.

Most patients with panic disorder also develop a pattern of fear and avoidance of specific situations

in which having a panic attack would be particularly distressing. Common agoraphobic situations

include driving, enclosed spaces such as elevators and airplanes, and public places such as malls or

grocery stores. Patients are encouraged to confront these situations during a phase of CBT called

situational or in vivo exposure. Typically, patients develop a “fear and avoidance hierarchy” that

lists situations by their level of difficulty. Through the course of CBT, they gradually confront each

situation repeatedly until their level of fear subsides. The goal of situational exposure is to facilitate

habituation, or the natural abatement of fear that occurs with repeated exposure to the same

situation. In vivo exposures can be conducted between sessions by the patient alone or within

sessions with the assistance of the therapist. Preliminary studies also suggest that virtual reality

technology can be used to expose patients to feared situations, with reductions in fear that may

approximate those achieved with in vivo techniques (Pull 2005).

Relapse Prevention

Most patients with panic disorder have experienced a significant alleviation of panic disorder

symptoms by the end of a standard course of CBT. The final few sessions of treatment generally

focus on consolidating skills and increasing independence. Therapists remind patients that their

“old habits” of anxious thinking and behavior are still quite strong and that continued practice of

CBT skills is necessary in order to maintain and extend improvement. Patients are encouraged to

become their own therapists by setting aside time each day to work on cognitive restructuring or

exposure exercises. The therapist normalizes and anticipates that the patient will experience

“lapses,” or times when panic symptoms or anxious avoidance returns. In their final collaboration,

the therapist and patient work together to develop a specific relapse prevention plan that provides

a blueprint for how to intervene quickly when lapses are detected. The goal of this phase of CBT is

to reduce the likelihood of relapse (return to pretreatment symptom levels) following treatment

withdrawal.

Other Components of Cognitive-Behavioral Therapy

Many CBT protocols have taught patients breathing retraining (BR) or relaxation strategies for

alleviating physical symptoms of panic disorder. These techniques provide short-term relief from

anxiety symptoms without necessarily addressing the diatheses that make persons vulnerable to

panic disorder, causing some experts to question their value. Indeed, using BR to alleviate panic

symptoms runs counter to the core message of CBT: that physical sensations associated with

anxiety are harmless and do not need to be avoided. Concern also exists about BR becoming a

“safety behavior” that patients rely on to get through anxiety-provoking situations. Safety

behaviors are hypothesized to maintain fear of physical symptoms (and therefore panic disorder) in

the long term. For this reason, BR is sometimes viewed as counterproductive to the goals of CBT

(e.g., Schmidt et al. 2000). Given the evidence that BR may be an extraneous (or detrimental)

component of CBT, it should be de-emphasized in favor of other CBT skills that promote long-termPrint: Chapter 29. Panic Disorder

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resolution of panic disorder symptoms.

Combining Cognitive-Behavioral Therapy and Pharmacotherapy

Combination Treatment

A recent multisite study of treatment for panic disorder provided the most systematic examination

of the effects of combining CBT and medication to date (Barlow et al. 2000). Four treatment sites

were used in this investigation: two with more commitment to CBT and two with more allegiance to

pharmacotherapy. The RCT compared the acute and long-term effects of CBT alone, imipramine plus

medical management, the combination of CBT plus imipramine, pill placebo plus medical

management, and the combination of CBT and pill placebo. Individuals who were classified as

responders to 11 sessions of acute treatment received 6 months of maintenance treatment (one

session monthly of whichever treatment they received in the acute phase).

All four active treatment conditions were superior to pill placebo. There were no significant

differences in the effects of CBT alone and imipramine alone in the acute or maintenance phases of

the study. The combination of CBT and imipramine produced mixed results, and only limited

benefits over monotherapy were observed. More improvement was seen in the CBT plus imipramine

group than in the CBT alone group on some posttreatment measures; however, the CBT plus

imipramine combination was never superior to CBT plus placebo. This suggests that the short-term

benefit of adding imipramine to CBT approximated a placebo effect. By the end of the 6-month

maintenance phase, the combination of CBT and imipramine produced the best response (superior

to CBT alone and CBT plus placebo); however, CBT plus imipramine also was associated with the

highest relapse rate 6 months after treatment withdrawal. The researchers concluded that addition

of CBT did not help reduce relapse following imipramine discontinuation, and addition of

imipramine actually appeared to reduce the durability of the effect of CBT. At best, combination

treatment appeared to produce a superior short-term response; however, this appeared to have

been at the expense of greater relapse following withdrawal of CBT (Barlow et al. 2000).

The results of the multicenter study suggest that more treatment is not necessarily better

treatment when it comes to panic disorder. For patients who are motivated for psychological

treatment, CBT alone appears to be at least as good a choice as combination treatment. For patients

who prefer pharmacotherapy, addition of concurrent CBT does not necessarily address the problem

of relapse after treatment withdrawal. However, it is important to note that the study results were

specific to the acute combined treatment with Panic Control Treatment (Barlow et al. 1989) and

imipramine. Combinations of other variants of CBT and medication and other time sequences may

produce different outcomes. In addition, as we discuss below, CBT can be very helpful for

individuals who are motivated to discontinue medications for panic disorder.

Use of Cognitive-Behavioral Therapy to Aid in Medication Discontinuation

Many patients who take medications for panic disorder wish to terminate pharmacotherapy at some

point. Reasons for medication discontinuation may be practical (e.g., cost), medical (e.g., side

effects), or personal (e.g., dislike of being “dependent” on medication). As noted earlier in this

chapter, benzodiazepines are effective in treating the symptoms of panic disorder but are

notoriously difficult for some patients to discontinue. The characteristic benzodiazepine withdrawal

syndrome includes nervousness, irritability, sleep disturbance, dizziness, and tremor. Several of

these symptoms are precisely those that can trigger panic attacks in panic disorder sufferers.

Several independent RCTs have shown that CBT is more beneficial than supportive medical

management in helping patients to discontinue benzodiazepines (Otto et al. 1993; Spiegel et al.

1994). The majority of patients who receive CBT while completing a benzodiazepine taper are

successful in discontinuing medication use by the end of acute treatment (usually 10–12 sessions).

A long-term follow-up study of patients from two benzodiazepine discontinuation studies

demonstrated that approximately 75% of patients who received CBT did not require any further

treatment for panic disorder during the subsequent 2–5 years (T. J. Bruce et al. 1999). By contrast,Print: Chapter 29. Panic Disorder

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70% of patients who received the same taper program with supportive medical management

required further treatment for panic disorder during this interval.

SSRIs are now widely recommended as the preferred form of pharmacotherapy for panic disorder

(American Psychiatric Association Work Group on Panic Disorder 1998). Although SSRIs may not be

associated with the same degree of physiological dependence as benzodiazepines, patients may

nevertheless find them hard to discontinue and may relapse after treatment withdrawal. Therefore,

the question of whether CBT can aid patients in SSRI discontinuation is pertinent. In one case

series (Whittal et al. 2001), 8 patients taking SSRIs were treated with CBT in a group setting. The

treatment focused on interoceptive exposure and cognitive restructuring and specifically addressed

issues related to medication discontinuation. Medication taper was gradual and was coordinated

with the referring physician. All 8 patients were able to discontinue their SSRI medications during

the 11-session course of CBT. In another study, 21 patients with panic disorder on stable doses of

SSRIs were assigned to 12 weeks of group CBT and then were randomized to either discontinue or

keep taking their SSRI at week 8 of treatment (Schmidt et al. 2002). The two groups did equally

well at posttreatment and follow-up 6 months later, suggesting that antidepressants may be

discontinued when patients receive CBT.

Use of Cognitive-Behavioral Therapy With Medication Nonresponders

There are no published RCTs that have tested the efficacy of CBT in patients with panic disorder

failing to respond to pharmacotherapy (or vice versa). This is surprising given that CBT and

pharmacotherapy are two very different, yet equally efficacious, treatments for panic disorder.

More research is needed to determine whether CBT can be used successfully in patients who remain

symptomatic after a pharmacotherapy trial, and vice versa.

Overcoming Barriers to Successful Implementation of Cognitive-Behavioral

Therapy

Transportability From Research to Practice Settings

One barrier to utilization of CBT may be doubts that the results of RCTs will generalize to service

settings. Differences may exist between research- and service-oriented settings in clientele,

resources, and treatment providers; therefore, it is important to extend research on CBT into more

practice-oriented settings. A study of 81 community mental health center (CMHC) patients showed

that they achieved as much benefit from a 15-session CBT protocol as participants in stringently

controlled efficacy studies (Wade et al. 1998). In the CMHC sample, 87% of CBT completers were

panic free at posttreatment. These patients manifested significant improvement on measures of

anxiety, agoraphobia, and depression and decreased their use of benzodiazepines. These results

suggest that the benefits of CBT are not restricted to clinicians or patients who are willing to

conform to the stringent formats that accompany research studies.

A recent multicenter trial also investigated the effectiveness of combined CBT and

pharmacotherapy delivered in primary care settings (Roy-Byrne et al. 2005). Patients were

randomized either to treatment as usual or to an intervention that provided up to 6 sessions of CBT

plus algorithm-based pharmacotherapy. To maximize comparability to typical primary care settings,

the clinicians who delivered CBT were behavioral health specialists who were mostly naive to CBT

prior to their training for the study. Results showed that patients who received CBT plus

pharmacotherapy achieved higher rates of remission and response than the group who received

standard care. They also scored lower on measures of disability. The superiority of the combined

intervention was observed at all assessment points of the study (with the longest follow-up

occurring 12 months postbaseline). Moreover, the authors concluded that, based on several aspects

of the data, “the improved outcomes for the intervention group might be attributed primarily to the

CBT component of the intervention” (Roy-Byrne et al. 2005, p. 295). The beneficial effects of CBT

observed in this study provide additional evidence that CBT can be adapted to the demands of

typical practice settings.

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Delivery of mental health care is increasingly constrained by the need to conserve resources such

as therapist time. Although CBT is a relatively brief psychosocial treatment, recent efforts have

been made to streamline it without decreasing efficacy. A 5-session (augmented with self-study)

version of CBT for panic disorder has been directly compared to a standard 12-session CBT protocol

and waiting list in an RCT (Clark et al. 1999). The abbreviated and full CBT protocols both produced

clinically significant improvements, with no differences between groups at 3- and 12-month

follow-ups. In both treatment groups, 71%–79% of patients were panic free and had achieved high

end-state functioning at posttreatment and 12-month follow-up. Therefore, self-study may be used

to decrease the amount of therapist time necessary to deliver effective CBT.

Patients also face economic and geographic barriers to obtaining CBT. Treatments that make use of

self-help materials may help overcome these issues. Studies have been conducted that evaluate the

impact of fully self-administered treatments and predominantly self-administered treatments with

minimal therapist contact. One RCT failed to show differences between fully self-administered CBT

bibliotherapy, self-monitoring, and wait-list control groups on measures of panic disorder severity

(Febbraro et al. 1999). Moreover, many patients dropped out of this study, suggesting that patients

may find it difficult to continue CBT without any support from a professional.

Results are much more encouraging when self-directed CBT treatments are combined with minimal

therapist contact. Minimal therapist contact typically includes brief phone calls or meetings to

provide encouragement, clarify treatment materials, and troubleshoot problems. Several trials have

shown that CBT-oriented bibliotherapy with minimal therapist contact is superior to a wait-list

control condition and no less effective than traditional therapist-administered CBT. In addition,

change with these protocols has been clinically significant and maintained over follow-up intervals

of up to 8 months (for a review, see Newman et al. 2003). Overall, self-administered CBT

treatments with minimal therapist contact are considered effective treatments for panic disorder,

although more extensive therapist contact may be required for patients with severe agoraphobia

(Newman et al. 2003).

Most investigations of self-administered CBT have focused on bibliotherapy; however,

computer-assisted therapy is another option under study. One Internet-delivered self-help program

has been shown to produce superior outcomes relative to a wait-list control group (Calbring et al.

2001). This program consisted of sequential modules that took patients through the major

components of CBT for panic disorder. Patients read information that explained each module and

completed a quiz to assess their comprehension. They also were provided forms for homework

assignments, and minimal therapist contact was provided via e-mail to help patients implement the

treatment successfully. Patients who completed the Internet program manifested significant

decreases in frequency, intensity, and duration of panic attacks. They also experienced relief from

daily anxiety, uncomfortable somatic sensations, anxious thoughts, agoraphobic avoidance, and

depression (Calbring et al. 2001).

Other Forms of Psychological Treatment for Panic Disorder

Psychodynamic Psychotherapy

There is some controlled (Wiborg and Dahl 1996) and uncontrolled (Milrod et al. 2001) evidence

supporting psychodynamic therapies specifically formulated for panic, but the RCTs that have

established the efficacy of pharmacotherapy and CBT are not available for psychodynamic

psychotherapy. However, psychodynamic psychotherapy remains a popular mode of nonmedication

treatment for psychiatric problems, and many patients with panic disorder may receive this type of

intervention in the community. Therefore, it is important to review the existing literature on the

efficacy of this method.

Evidence suggests that brief insight-oriented psychotherapy is inferior to medication and CBT in the

treatment of panic disorder (Craske et al. 1995; Shear et al. 2001). One of these studies examined

the efficacy of “emotion-focused psychotherapy” (EFP), a treatment that featured exploration,Print: Chapter 29. Panic Disorder

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empathic listening, and supportive strategies (Shear et al. 2001). EFP techniques were based on

the conceptualization of panic attacks as reactions to unrecognized emotions that stem from

interpersonal problems (e.g., fears of abandonment). Patients receiving EFP were aided in

identifying and managing painful emotions and difficult life situations so that they might achieve

insight into the emotional and relational sources of their panic symptoms. The efficacy study

compared 3 months of weekly EFP sessions with equal doses of CBT, imipramine, and placebo. EFP

produced an inferior rate of acute treatment response when compared with the other active

treatments (52% EFP patients recovered vs. 82% of CBT patients and 92% of imipramine patients).

Patients receiving EFP also had higher panic disorder severity and anxiety sensitivity scores at

posttreatment. Of the individuals who responded to EFP, 15% relapsed at 6-month follow-up

(compared with 22% for imipramine and 0% for CBT). In general, the effect of EFP on panic

disorder symptoms was approximately equivalent to placebo. These results led the researchers to

warn that although it is a common form of treatment in the community, nonspecific psychotherapy

is suboptimal treatment for panic disorder (Shear et al. 2001).

Eye Movement Desensitization and Reprocessing

EMDR is both a popular and a controversial psychological treatment for posttraumatic stress

disorder. Proponents of EMDR have suggested that it may also be adapted to treat other clinical

problems, including panic disorder. One RCT has been published in which it was established that six

sessions of EMDR were superior to a wait-list control condition (Feske and Goldstein 1997). At

posttreatment, large differences were found between the EMDR and wait-list control groups on

panic frequency, concerns about physical symptoms, agoraphobia, and social concerns. However,

additional analyses showed that while EMDR was statistically superior to the wait-list control

group, the clinical significance of the impact of EMDR was questionable. Only 1 of 15 EMDR patients

achieved high end-state functioning at posttreatment, and none met criteria for high end-state

functioning at 3-month follow-up. Although the criteria for high end-state functioning were quite

stringent, these results naturally temper enthusiasm for the use of EMDR in treating panic disorder.

In addition, EMDR needs to be compared to a credible placebo and other established treatments

(e.g., medication, CBT) before it can be recommended as a treatment for panic disorder (Feske and

Goldstein 1997).

CONCLUSION

Panic disorder is a prevalent serious condition that deleteriously impacts the lives of individuals

who suffer from it. A great variety of pharmacological and psychological treatments are available

for panic disorder, and some of these have strong evidence of their efficacy and safety. Among the

available treatment options, SSRIs and CBT have the most substantial evidence for utility, with

much of this evidence having accrued over the past 15 years. But many questions about optimal

approaches to therapy for panic disorder remain unanswered. Which treatment(s) should be

offered first to patients (i.e., pharmacological or psychological)? Should patient preference be the

only consideration in this regard, or can other predictors of outcome to the various treatment

modalities be developed? What is the ideal approach for patients with panic disorder who fail their

initial treatment of preference? What about approaches for patients with panic disorder who are

refractory to standard treatments? Under what circumstances should pharmacological and

psychological treatments be combined? How can CBT approaches for panic disorder be more widely

disseminated? How can we improve the care for patients with panic disorder treated in primary

care settings? These and other questions will drive the therapeutic research agenda in panic

disorder for years to come.

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