A Time-Series Study of the Treatment of Panic Disorder

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DOI: 10.1177/15346501103919012011 10: 3 originally published online 6 December 2010Clinical Case StudiesSara R. Elkins and Todd M. Moore

A Time-Series Study of the Treatment of Panic Disorder

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A Time-Series Studyof the Treatment ofPanic Disorder

Sara R. Elkins1 and Todd M. Moore1

Abstract

Although efficacy of cognitive-behavioral therapy (CBT) in the treatment of panic disorder has

been well documented, far fewer studies have investigated treatment outcome for panic disorder

among real-world patients with a range of complicating factors. The current study employeda time-series approach to examine the effectiveness of CBT for panic disorder for a patient

who sought services at a university psychology clinic. Following a 16-session CBT treatmentprotocol, the patient demonstrated significant decreases in self-reported distress, anxiety andpanic symptoms, and worry about having a panic attack. Several qualitative changes were also

notable following termination, including decreased tobacco and psychiatric medication usageas well as decreased comorbid depressive symptoms and agoraphobia behaviors. Outcomeswere maintained 9 months post treatment. This study supports effectiveness of implementing

a CBT approach to the treatment of panic disorder with agoraphobia among complex patients.Treatment implications and applications are discussed.

Keywords

time-series, panic disorder, agoraphobia, cognitive-behavioral therapy, treatment outcome

1 Theoretical and Research Basis

Panic disorder is a serious condition with 12-month and lifetime prevalence rates of approximately2.7% and 4.7%, respectively (Kessler, Berglund, Demler, Jin, & Walters, 2005). Panic disorder

with or without agoraphobia can be associated with a number of impairments in important areas of

functioning, including increased risk for physical (Zaubler & Katon, 1996) and emotional health

problems (Andrade, Eaton, & Chilcoat, 1996; Kessler, Stein, & Berglund, 1998; Roy-Byrne &Katon, 2000); impaired social, relational, and occupational functioning (Altamura, Santini, Salvadori,

& Mundo, 2005); substance abuse (Altamura, Santini, Salvadori, & Mundo, 2005); suicidal behav-

ior (Weissman, Klerman, Markowitz, & Ouellette, 1989); and greater use of medical and psychiat-

ric resources than individuals without panic disorder (Zaubler & Katon, 1998).

Contemporary cognitive-behavioral approaches treat panic disorder using a number of spe-cific components, including information on panic, relaxation and breathing retraining, cognitive

restructuring, interoceptive and in vivo exposure, and fading of safety behaviors (Margraf, Barlow,

Clark, & Telch, 1993). Efficacy of cognitive-behavioral therapy (CBT) for panic disorder has

1University of Tennessee, Knoxville, TN

Corresponding Author:

Sara R. Elkins, University of Tennessee, Department of Psychology, Austin Peay Building, Knoxville, TN 37996

Email: [email protected]

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4 Clinical Case Studies 10(1)

been well documented across a number of independent evaluations. Findings show that CBT for

panic disorder typically produces high panic-free rates (70%-80%, for example, Barlow, Craske,Cerny, & Klosko, 1989) and that these rates are well maintained over 2-year follow-up intervals

(Craske, Brown, & Barlow, 1991). In contrast, although medication approaches to the treatment

of panic disorder, such as benzodiazepine treatment, have demonstrated comparable acute effi-cacy, studies have shown that the benefits of treatment decrease once medication is discontinued

(e.g., Ballenger et al., 1988; Pecknold, Swinson, Kuch, & Lewis, 1988; Rickels, Schweizer,

Weiss, & Zavodnick, 1993; Spiegel & Bruce, 1997). In addition, several studies have demon-

strated higher relapse rates among individuals treated with medication alone than those who

received CBT or a combination of CBT and pharmacotherapy (e.g., Gould, Otto, & Pollack,

1995; Roy-Byrne et al., 2005). Moreover, CBT has been shown to be effective even in cases ofindividuals who suffer from nocturnal panic attacks and comorbid conditions such as depression

or other anxiety disorders, or when used in studies of discontinuation from high-potency benzo-diazepines (Brown, Antony, & Barlow, 1995; Craske, Lang, Aikins, & Mystkowski, 2005; Otto,

Pollack, Sachs, Reiter, & Rosenbaum, 1993).

Randomized controlled studies on agoraphobia have also consistently established the efficacy

of CBT for agoraphobia. These studies have shown that after an average of 12 treatments, 69%

of patients demonstrate some level of clinically significant improvement, across a number of

different areas, by posttreatment (Craske, 1999) and at follow-up assessments. For example,Fava, Zielezny, Savron, and Grandi (1995) demonstrated that only 18.5% of their symptom-free

patients relapsed over a 5- to 7-year period following exposure treatment for agoraphobia.

Although there is much agreement regarding the efficacy of CBT for panic disorder, it can be

argued that the results obtained from efficacy studies cannot be assumed to generalize to other

clinical settings, populations, and treatment providers (Hollon, 1996; Jacobson & Christensen,

1996; Seligman, 1996). Important factors in this distinction include comorbidity and severity of

disorders experienced by clinicians (e.g., extreme agoraphobia that may limit consistent clinicattendance) but excluded from participation in many randomized controlled trials of CBT for

panic disorder. The effectiveness study method, therefore, adds the additional step of determin-

ing generalizability of the treatment and answers the question for whom does such treatment

work? The importance of the effectiveness study method is therefore highlighted in an era of

rising health care costs and declining benefits for patients, as it provides vital knowledge about

individual factors important in treatment and maintenance of treatment gains.

Therefore, the present study will utilize a time-series design (described below) to investigate the

effectiveness of a cognitive behavioral treatment for panic disorder with an adult patient treated in

an outpatient clinic. Although this study does not claim to be a controlled trial of the effectiveness

of CBT for panic disorder, the present article aims to systematically examine this treatment approachin routine clinical practice. The following treatment outcome hypotheses were considered:

Hypothesis 1: A cognitive-behavioral approach would be effective for the treatment of

panic disorder. At termination, the patients five identified symptom clustersnumber

of panic attacks, worry about panic attacks, avoidance behaviors, overall anxiety level,

and overall distresswould be decreased relative to before therapy began.

Hypothesis 2: Treatment gains would be maintained at all follow-up sessions.

One additional exploratory hypothesis was considered:

Hypothesis 3: Will decreases in the five measured symptoms (overall distress, average anxi-

ety, worry about panic attacks, number of panic attacks, and avoidance, described below)

occur simultaneously or will changes in one symptom precede changes in other symptoms?



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Elkins and Moore 5

Although a similar article has been published in this journal demonstrating the effectiveness

of a CBT approach for panic disorder (Murad & Luiselli, 2002), the present study adds complexity

to the previous effectiveness study in significant ways. First, the present study adds the

complexity of time-series statistical analyses that provide additional scrutiny in examining

clinical outcomes. In addition, follow-up data in the present study was collected at 1, 6, 8, and9 months post treatment as compared to a follow-up period of only 3 months in the Murad and

Luiselli (2002) study, which provides important data related to the long-term benefits and costeffectiveness of this treatment. Also related to cost effectiveness is the demonstration that this

treatment can be applied successfully across relatively few treatment sessions (16 sessions in our

study as compared to 25 sessions in the Murad and Luiselli [2002] study). These differences

indicate the relative contribution of the current study to the literature on the effectiveness of

CBT for panic disorder among real-world clinical patients.

2 Case Presentation

Anthony (patients name has been changed to protect confidentiality) is a 36-year-old Whitemale who sought therapy at the University of Tennessee Psychological Clinic to treat symptoms

of anxiety and panic attacks.

3 Presenting Complaints

At the time of intake, Anthony reported experiencing a number of panic and anxiety symptoms

as well as agoraphobic behaviors. Typical panic symptoms experienced included racing

thoughts, heart palpitations, sweating, shakiness, shortness of breath, numbness from pelvis to

brain, feeling as if he was losing control, feelings of unreality, hyperattentiveness, a fear of uri-

nation during an attack, and he admits he often lost control of urination during a panic attack.Anthonys panic attacks were triggered primarily when riding with someone or driving alone in

his car. Attacks typically de-escalated when he returned home, which he identified as his safeplace. Typical attacks lasted between 5 and 30 min, but he also had several experiences where

attacks seemed to last for the better part of a day. Anthony also reported a significant amount of

anticipatory anxiety and agoraphobic avoidance behavior in situations that had triggered attacks

in the past or were similar in some way to situations where he had experienced a past panic

attack. These situations included being in hot rooms or cars, riding in elevators, being in a shop-

ping mall or other crowded place, hiking, camping, waiting in line, riding as a passenger or

driving with a passenger in a car, boating, and watching particularly arousing television pro-

grams (e.g., Deadliest Catch).At intake, Anthony was receiving psychiatric services to treat his panic attacks, but despite

medication, his panic attacks were becoming more frequent and intense. His goals for therapy

were to deal with attacks to the point Im no longer thinking of them or scheduling around when

I think they may happen and no longer avoid situations for fear of having a panic attack. He

also hoped to decrease his reliance on medication and make behavioral changes that would pre-

vent the return of panic symptoms.

4 History

Anthony grew up in Knoxville, Tennessee. He was the youngest of four children, and separated

by 8 years to his closest-in-age sibling. He lived within an intact family, although he recalled thathis parents experienced marital difficulties during his childhood and early adolescence (age 9-14).

Anthony performed well in school, maintaining a B average or above for all years of schooling.

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He attended Pellissippi State Community College and earned an associates degree in business

management. Anthony maintains a close relationship with his siblings and parents and works in

the construction business with his father. He is active in social activities and has a wide social

support network of family and friends from church and his Boy Scout troop (Anthony serves as

a scoutmaster). Anthony expressed some disappointment that he has not yet found a lifelongromantic partner, and he expressed a desire to begin dating seriously and start a family.

Anthony experienced his first panic attack in 1992 at the age of 21, triggered by a driving trip

to a church camp where he was scheduled to be a counselor. This attack appeared to be triggered

by anxiety related to his role at the camp (i.e., involving public speaking) and included a number

of cognitive and somatic symptoms (e.g., shortness of breath, heart palpitations, sweating, feel-

ing as if he was losing control, and a fear of dying). He describes the attack as quite severe, with

intense symptoms lasting almost 1 hr. He had only a handful of panic attacks during the next

5 years but experienced a second severe attack at age 26 during a long drive following a fishing

trip to Florida. This attack appeared to come out of the blue, and Anthony was unable to pin-

point why panic symptoms arose. For the next 10 years, Anthonys panic attacks continued to

increase in frequency and severity. In February of 2008, Anthony recalls that the bottom

dropped out and he began to have 3 to 4 panic attacks per week, each more severe and frighten-

ing than the last. He described this as a particularly stressful time in his work because of the crisis

within the housing market, and he began to have attacks frequently at work, on the way to job

sites, and during interviews with potential clients.

Anthony had received medication management for panic symptoms since 1999 but reported

only short-term effectiveness in the management of symptoms and noted that symptoms returnedwith discontinuation of each medication. Previous medications included Elucibar, Paxil, Prozac,

and Klonopin. At the time of treatment, Anthony was taking Xanax prescribed as needed for

panic symptoms (0.5mg, up to 3 times daily) as well as Effexor for depressive symptoms (75mg,

2 times daily). Additional medical concerns included elevated blood pressure, and Anthonyreported heavy smokeless tobacco use (equivalent to four packs of cigarettes per day) for the last

10 years. He also reported moderate caffeine use (six caffeinated beverages daily). Anthony had

received no prior psychotherapy at any time in his life.

5 Assessment

Baseline Measures

Several measures were provided at baseline to obtain an accurate symptom picture of panic and

agoraphobia as well as to rule out other clinical symptomatology.Panic symptoms were measured with the Panic Attack Questionnairerevised (PAQ-R; Cox,

Norton, & Swinson, 1992). The PAQ-R gathers information on the phenomenology of an indi-viduals panic attacks, including family history, onset and frequency, situational triggers, and

coping styles. The measure also instructs individuals to respond to a list of 26 Diagnostic and

statistical manual of mental disorders (DSM) symptoms that address physical and cognitive

aspects of panic. Internal consistency, construct validity, and factor structure have been shown for

this measure (Bouchard, Pelletier, Gauthier, Cote, & Laberge, 1997). Anthonys responses indi-

cated a family history of panic attacks (brother) and a high frequency and severity of panic symp-

toms (although this measure does not provide a specific score or cutoff). He reported experiencing

approximately 20 panic attacks within the past year, 7 within the past month, and 3 within the

week prior to beginning therapy. Situational triggers listed included traveling, fishing, riding in

vehicles with friends, or situations where it would be difficult to leave if a panic attack occurred.



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Elkins and Moore 7

In addition to the above-listed, research-based measure, Anthony was administered the Min-nesota Multiphasic Personality Inventory2 (MMPI-2) as well as the Anxiety Disorders Inter-view Schedule (ADIS-IV) Clinical Interview.

The MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) is a self-report

personality assessment designed to evaluate psychopathology and assist with the diagnosis ofmental disorders as well as provide information related to the personality profile of an individual.

The MMPI-2 is composed of 567 true or false items assessing a wide range of clinical pathologyand personality dimensions, and yields validity, clinical, and content scales. The MMPI-2 isconsidered the gold standard in personality assessment and has demonstrated moderate to high

internal consistency estimates for validity, clinical, and content scales as well as high testretest

reliability (Butcher et al., 1989). Anthonys results produced a valid clinical profile, indicating

that his scores are a good picture of his present level of personality functioning. Although Anthonys

results on the MMPI-2 did not produce any clinically significant elevations of pathology (65),it is valuable to consider the relative frequency of endorsed dimensions within his personality

profile. His two highest endorsed clinical scales included hysteria (Hy, T-score = 57) and psych-

asthenia (Pt, T-score = 57), indicating a profile with the following descriptors: overcontrolled,tense, anxious, passive, ingratiating, somatization. This profile suggests a moderate anxiety disor-

der in a psychologically naive individual who is likely to develop hysterical symptomatology in

response to psychological stress. In addition, Anthonys results indicated a clinically significant

elevation (T-score = 70) for the anxiety content scale, and he endorsed 10 critical items withinthis scale.

The ADIS-IV (Di Nardo, Brown, & Barlow, 1994) is a structured clinical interview designedto evaluate the presence of anxiety disorders and allow differential diagnosis among anxiety

disorders, based onDiagnostic and statistical manual of mental disorders (4th ed., text revision;

DSM-IV-TR; American Psychiatric Association, 2000) criteria. The ADIS-IV has demonstrated

good to excellent reliability for the majority ofDSM-IVanxiety categories (Brown, Di Nardo,Lehman, & Campbell, 2001) and convergent and discriminant validity (Brown, Chorpita, &

Barlow, 1998). Based on his responses on this measure, Anthony met criteria for panic disorder

with agoraphobia.

Diagnosis

Based on theDSM-IV-TR diagnostic system, Anthony met seven of the symptom criteria for a

panic attack (four or more symptoms required for diagnosis), including heart palpitations, sweat-

ing, shakiness, shortness of breath, numbness, feelings of losing control, and derealization. In

addition, he met criteria for panic disorder, characterized by (a) recurrent panic attacks, (b) unex-pected attacks, (c) at least 1 month of persistent worry about the recurrence of panic symptoms or

consequences associated with exhibiting panic symptoms, and (d) significant behavioral changes

related to the attacks. Anthony also met criteria for agoraphobia, as he repeatedly avoided situa-

tions where he feared having an attack or where he believed escape would be difficult.

Differential diagnosis would suggest one additional diagnostic category to be investigated.

Although Anthony met several of the criteria for social phobia, his avoidance was not limited to

social situations. In fact, Anthonys panic attacks often occurred when he was alone, therefore he

actively limited his amount of time spent alone, preferring to surround himself with a wide sup-

port network of friends and family. In addition, Anthony reported subclinical depression that did

not meet criteria for diagnosis at that time. However, his reported quantity of nicotine (equivalent

to four packs of cigarettes per day), as well as associated features of tolerance and withdrawal,

indicate he also met criteria for nicotine dependence. Therefore, based on the results from



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baseline measures and self-report provided during the initial intake interview, Anthony metcriteria for the following diagnostic conditions:

Diagnostic code Diagnostic category

Axis I 300.21 Panic disorder with agoraphobia305.10 Nicotine dependence

Axis II V71.09 NoneAxis III Elevated blood pressure

Axis IV Occupational stressors

Axis V GAF Current: 50Highest past year: 65

It was therefore recommended that Anthony begin individual cognitive behavioral psycho-

therapy to treat panic and agoraphobia symptoms.

6 Case Conceptualization

Studies on the etiology of panic disorder have emphasized a psychobiological conceptualization

of the development of the disorder (Barlow, 2000; Craske, 2003). Genetically, studies have indi-

cated that panic disorder has substantial genetic heterogeneity and that a complex linkage of genes

may participate to confer vulnerability through yet-to-be determined pathways. From a psycho-logical perspective, the initial panic attack is viewed from a stress-diathesis model, such that thefirst attack is prone to occur within a stressful situation (Craske & Barlow, 2007a). Indeed, Anthonys

initial attack occurred during a trip where he was scheduled to speak in a group setting, and he

endorsed significant anxiety related to this event, displaying a range of cognitive and physiologi-cal symptoms of panic. According to the psychobiological conceptualization of panic, attacks are

maintained because of the fear of fear, or fear of bodily sensations associated with panic, that

develops after the initial attack. This fear is reinforced through interoceptive conditioning (i.e.,

learned anxiety about internal states through aversive associations) and the misappraisal of bodily

sensations as dangerous or catastrophic. In addition, anxiety becomes tied to specific contexts in

which panic attacks have previously occurred or where escape might be difficult, thereby reinforc-

ing avoidance behaviors related to these contexts. Consistent with the theory, Anthonys attacks

appeared to be maintained by fear that his symptoms were harmful (predicted impending cardiac

problems) and that these attacks would occur while he was in confined spaces or in the presence

of others. These erroneous beliefs contributed to avoidance of malls, restaurants, church meetings,or any other setting where he would become embarrassed by panic symptoms or escape might be

difficult. His belief about the harmfulness of his symptoms also contributed to his reliance on fast-acting medication to reduce his symptoms (and use of the medication bottle as a safety signal,

even if he did not consume the medication). As Anthony continued to restrict his social encounters

and other life behaviors, negative cognitions became more frequent and more catastrophic, thereby

strengthening the connection between symptoms and negative outcomes.

7 Course of Treatment and Assessment of Progress

Treatment Measures

The treatment protocol utilized an A-B outcome design with a pretreatment baseline phase, treat-

ment phase, and follow-up phase to test whether treatment gains were maintained.



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Elkins and Moore 9

At intake, Anthony was administered the Outcome Questionnaire 45.2 (OQ-45.2; Lambert,Gregersen, & Burlingame, 2004) as a baseline measure of overall distress. The OQ-45.2 is a45-item measure used to measure patient progress (symptom reduction) in therapy by repeated

administration during the course of treatment, at termination, and at follow-up sessions. Indi-

vidual items measure symptom status across a wide variety of disorders and assess personal andsocial factors related to overall quality of life. Several studies report that the OQ-45 is a highly

reliable measure and report high criterion validity with other measures of psychological distress,

interpersonal functioning, and social performance (Lambert et al., 1996; Lambert, Gregersen, &

Burlingame, 2004; Umphress, Lambert, Smart, Barlow, & Clouse, 1997). The OQ-45 has also

demonstrated excellent sensitivity to change during outpatient psychotherapy (Lambert, Okiishi,

Finch, & Johnson, 1998; Vermeersch et al., 2004).

In addition, following the collection of interview data, five questions were developed in

cooperation with Anthony and specified to address his most prevalent reported symptoms.

Anthony was then provided the forms with the five listed questions and he was asked to com-

plete questions once daily. The questions were intended to measure treatment outcome and

were completed by Anthony during the baseline period and throughout the course of treatment,

termination, and follow-up. Questions were based on theDSM-IV-TR criteria for panic disorderwith agoraphobia. The first three questions were measured on a Likert-type scale ranging from

1 (not at all) to 9 (extremely) and included the following:

1. Overall distress (this is a general overall rating of how you felt)

2. Overall level of anxiety

3. Level of worry about having a panic attack

The fourth question was recorded as a discrete number with no top range.

4. How many panic attacks did you experience today? Please list the number of panic

attacks experienced (If one or more panic attacks occurred, please complete a panic

attack record for each attack).

The fifth question required a dichotomous (yes or no) response.

5. Was there a time when you did not do something you wanted to do because of worry

about having a panic attack? If yes, please explain on a separate sheet of paper.

Following a 14-day baseline period of answering daily questions, Anthony began thetreatment phase, which lasted 16 sessions. Anthony returned the daily rating sheets when hecame to the weekly therapy session. The OQ-45.2 was administered monthly during thetreatment phase, at termination, and at four additional follow-up sessions (1, 6, 8, and 9 months;

8 month follow-up session was by patient request). Baseline observations were compared toobservations during the treatment phase as well as observations at follow-up.

Treatment Sessions

The cognitive behavioral treatment approach utilized for the study was based on the Mastery of

Your Anxiety and Panic manual by Craske and Barlow (2007a). This treatment is a well-estab-lished, evidence-based treatment approach that typically yields high panic-free rates at terminationand at subsequent follow-up visits, as long as 2 years from termination (Barlow, Craske, Cerny, &

Klosko, 1989; Brown & Barlow, 1995; Craske, Brown, & Barlow, 1991; Tsao, Mystkowski,



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Zucker, & Craske, 2002, 2005). Treatment is typically completed in between 12 and 15 sessions,

depending on the patients speed of comprehension and implementation of various tasks, level of

avoidance behavior (requiring additional sessions for exposure practices), and the presence of

coexisting disorders. Treatment sessions emphasize five main components, including education on

panic and agoraphobia, coping skills for panic symptoms (breathing retraining, muscle relaxation,positive visualization), cognitive skills (overestimations, catastrophic cognitions), interoceptive

and in vivo exposure, and consolidation and maintenance of progress. The therapy was delivered

by a clinical psychology doctoral student receiving training in CBT. Therapy was supervised by a

licensed clinical psychologist with training and experience in CBT.

The early stage of treatment involved education about the concepts of anxiety and panic. The

therapist provided a description of the three component system of panic and anxiety (i.e., physi-

cal sensations, thoughts, and behavior) and the difference between symptoms of panic and symp-

toms of anxiety, and decomposed a typical panic sequence with Anthony. The physiology of

panic was discussed and the adaptive function of anxiety was explored. This stage also included

discussion of daily monitoring of symptoms, and Anthony was provided an explanation and

rationale for use of the daily mood record to record symptoms of panic, anxiety, and depression.

He was also encouraged to utilize the panic attack record to aid him in noticing triggers and early

warning signs for his panic attacks, thus making attacks somewhat more predictable.

During the second phase of treatment, Anthony was taught physical coping skills that would

aid him in managing and reducing panic symptoms. A hyperventilation (i.e., overbreathing)

exercise was utilized to induce symptoms similar to a panic attack, and the physiology of over-

breathing and its relation to panic symptoms were discussed. The process of slowed diaphrag-

matic breathing utilizing a one-in-relax-out procedure as well as attention to the breaths wasdemonstrated by the therapist and practiced with Anthony in session. Anthony was also instructed

about the practice of progressive muscle relaxation, which helped him to gain better control of

physical tension produced by anxiety and involves deliberately applying tension to one musclegroup at a time and then releasing tension and directing attention to noticing and experiencing

the relaxation of these muscle groups. The final relaxation skill taught was positive visualization

that involved Anthony imagining himself successfully managing and surviving panic symptoms.

The third phase of treatment involved incorporation of cognitive coping skills for managing

and reducing panic symptoms. The therapist and Anthony analyzed current worry thoughts,

overestimations, and catastrophic thinking and discussed how to modify these types of thinking

patterns using analysis, alternative evidence, and prediction testing, as well as learning decatastro-

phizing strategies (e.g., so what statements). During this phase of treatment, the therapist also

instructed Anthony in in-session breathing practice with a distracting stimulus as well as applied

breathing practice when experiencing panic symptoms. At the end of this phase of treatment, thetherapist and Anthony established a hierarchy of agoraphobia situations that were ranked in

increasing order of anxiety. Situations avoided included driving, flying, waiting in lines, crowds,

restaurants, being long distances from home, hairdressers, long walks, boats, and elevators.

During the fourth phase of treatment, the techniques of interoceptive exposure and in vivo

exposure were explained, demonstrated, and practiced. This phase began with a period of plan-

ning for interoceptive exposure, which included a rationale for interoceptive exposure and the

benefits of learning new ways of responding to physical sensations. The therapist instructed

Anthony in in-session induction of panic-similar physical sensations and ranked these inductionsbased on similarity to those in a real panic attack and amount of anxiety these symptoms pro-

duced. Each exercise was performed until anxiety and fear were decreased to a mild level (2 or

below on a scale from 0 to 8). During between-session practices in this phase, Anthony reportedthat he had completed all symptom induction exercises while alone and was concerned that he

would not be able to reduce his anxiety if completing the exercises in front of others. The



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Elkins and Moore 11

therapist and Anthony discussed including a friend in his induction exercise to determine whether

he would be able to reduce his anxiety, and this was implemented in subsequent between -sessionpractices. During this phase of treatment, Anthony reported feeling more confident about his

ability to control his panic attacks using physical and cognitive strategies. Finally, the therapist

and Anthony worked together to create a natural activities hierarchy and determine graduatedtrials for between-session practices (e.g., hot stuffy rooms, hot stuffy car, camping). It was

explained that the physical sensations might be the same when completing the induction exer-

cises and natural activities exercises but that after repeated practice, his anxiety and fear about

the sensations would start to decrease for the natural activities just as for the induction exercises.

The therapist and Anthony also discussed reasons why panic might recur during treatment, par-

ticularly during symptom induction or in vivo exposure exercises.

In addition to interoceptive exercises, Anthony was also trained in exposure to feared agora-

phobia situations so that he might gain better tolerance of fear and anxiety symptoms. A hierarchy

of agoraphobia situations was created cooperatively with Anthony and practice situations were

initiated between sessions in a graduated fashion. Areas of difficulty and avoidance behavior were

addressed during therapy sessions as well as an analysis of what was learned from exposure prac-

tices. The final portion of the exposure component involved inducing physical sensations during

planned exposure exercises, which emphasized simultaneous exposure to internal and external

cues, in an attempt to prepare Anthony for what will be experienced in situations in the future.

The final phase of treatment involved a review of the main components of treatment, an

evaluation of progress made toward goals, discussion of strategies to maintain goals, and discus-

sion of long-term life goals. Anthony reported a belief that all therapeutic goals had been met,including reduction of panic and anxiety symptoms, reduction of depressive symptoms (which

was not a target of treatment), and an increase in his participation in previously avoided activi-

ties. Long-term life goals identified included go on a boating trip to Florida; make my busi-

ness successful and hopefully work less; find my life partner, get married, and start a family;and go, do, and function without ever having to think about panic.

Treatment Outcome Results

Tracking of symptom improvement relative to the psychological intervention was conducted

through simulation modeling analysis (SMA; Borckardt, 2008), a time-series analysis programfor short time-series data streams. SMA employs a bootstrapping methodology that enables anal-

ysis of symptom change with a relatively small number of observations per phase and accounts

for the autocorrelation inherently present in temporal research. SMA provides descriptive statis-

tics, Pearsons correlations, and level change statistics for baseline and treatment phases. Auto-correlation values for the overall data set (rather than individual values) were utilized in all tests

of level change to determine significance of treatment effects, per SMA recommendations indi-

cating this is the most conservative approach to reduce the Type I error rate (Borckardt, 2008).

Descriptive results examining mean comparisons of daily variables across baseline and treat-

ment phases revealed significant mean differences for each of the five measured variables, such

that levels of distress decreased between baseline and treatment phases (see Table 1). A Bonfer-

roni correction was employed to account for multiple comparisons, and p values 0.01 were

considered significant. Using this method, all of the measured daily variables remained signifi-

cant except for reported avoidance behaviors. In addition, regression slopes across baseline and

treatment demonstrated decreases for each of the five daily variables, and these trends are visu-

ally represented in Figures 1 to 5.

After controlling for autocorrelation present across time points, overall distress (R=-0.329,

p= .0002), average anxiety (R=-.353,p= .0006), average worry about having a panic attack



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Table 1. Descriptive Statistics and Pearsons Correlations for Daily Measures

Baseline (n= 16) Treatment (n= 140) Overall (N= 156)

M SD M SD r p

Overall distress 4.56 1.97 2.65 1.63 -.329 .0001Average anxiety 4.94 2.25 2.57 1.86 -.353 .0001

Average worry abouthaving a panic attack

8.75 0.66 2.64 2.24 -.655 .0001

Number of panic attacks 0.31 0.68 0.02 0.19 -.299 .006

Avoidance behaviors 0.25 0.43 0.08 0.27 -.176 .03

0

1

2

3

4

5

6

7

8

9

OverallDistress

I. Education

II. Relaxation

III. Cognitive Skills

IV. Exposure-Interoceptive

V. Exposure-In Vivo

I II III IV V

Figure 1. Daily ratings for overall distress across baseline and treatment

(R=-.655,p= .0001), and number of panic attacks (R=-.299,p= .0001) showed statistically

significant decreases between baseline and treatment phases, supporting significant treatment

effects for these variables not because of random error (see Table 2). The only daily mea-

sure that did not meet statistical significance (p= .01) was avoidance behaviors (R=-.176,

p= .0226), though the trend effect was in the expected direction (decreased from baseline to

treatment).

Monthly OQ-45.2 assessments were utilized during baseline, treatment, and follow-up phases.Although there was an insufficient number of follow-up data points for statistical analysis usingthe SMA program, visual analysis of the trend line (see Figure 6) demonstrates a decrease in

overall symptomatology from baseline (score = 63), to termination (score = 32), and last follow-up visit (score = 14). In addition, effect sizes were calculated for this measure from baseline to

treatment as well as from treatment to follow-up. Findings showed a large effect size from base-

line to treatment (Cohens d= 3.10, r= 0.84) and a moderate effect size from treatment to follow-up phases (Cohens d= 1.53, r= 0.61).



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Elkins and Moore 13

0

1

2

3

4

5

6

7

8

9

AverageAnxiety

I. Education

II. RelaxationIII. Cognitive Skills


V. Exposure-In Vivo

I II III IV V

Figure 2. Daily ratings for average anxiety across baseline and treatment

0

1

2

3

4

5

6

7

8

9

WorryAboutHavingaPanicAttack

I. Education

II. Relaxation



V. Exposure-In Vivo

I II III IV V

Figure 3. Daily ratings for worry about panic across baseline and treatment

Cross-lagged correlations were utilized to determine statistical patterns of symptom change

across treatment. Per patient report, the predominant and most negative symptom experienced

was worry about having future panic attacks. This is consistent with target symptom reporting



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0

1

2

3

NumberofPanicAttacks

I. Education

II. RelaxationIII. Cognitive Skills


V. Exposure-In Vivo

I II III IV V

Figure 4. Daily ratings for number of panic attacks across baseline and treatment

0

1

Av

oidanceBehaviors

I. Education

II. Relaxation


IV. Exposure -Interoceptive

V. Exposure -In Vivo

I II III IV V

Figure 5. Daily ratings for avoidance behaviors across baseline and treatment

across treatment, as the patient only experienced eight panic attacks throughout baseline and

treatment phases but reported high levels of anticipatory anxiety throughout baseline and much

of the treatment phase. In addition, this symptom exhibited the largest change over time (steepest



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Elkins and Moore 15

Table 2. Autocorrelations and Level Change From Baseline to Treatment Phases

Baseline (n= 16) Treatment (n= 140)Overall (N= 156)

Autocorrelation

(Lag-1) p

Autocorrelation

(Lag-1) p

Autocorrelation

(Lag-1) p

Levelchange

R p

Overall distress .213 .288 .611 .0001 .549 .0001 .329 .0002

Average anxiety .238 .103 .536 .0001 .556 .0001 .353 .0006

Average worryabout havinga panic attack

.086 .368 .637 .0001 .793 .0001 .655 .0001

Number ofpanic attacks

.148 .351 .395 .0040 .125 .0510 .299 .0001

Avoidancebehaviors

.022 .619 .212 .011 .189 .008 .176 .0226

0

10

20

30

40

50

60

70

OQ-45Tota

lScore

I. Start of Treatment Period

II. Start of Follow-Up Period

I II

Figure 6. Monthly ratings of overall distress on the OQ-45.2 across baseline, treatment, and follow-upphasesNote: OQ-45.2 = Outcome Questionnaire 45.2.

slope), and as such, level of worry about having a panic attack was cross-correlated with bothnumber of attacks experienced and reported avoidance behaviors. Reported levels of overall

distress and average anxiety demonstrated strong cross-correlations with worry about attacks

(distress and worry, r= .75; anxiety and worry, r= .80) and therefore were not cross-correlatedwith number of attacks and avoidance behaviors. A range of lags from -5 to +5 was employed,

and a Bonferroni correction was used to adjust for multiple comparisons based on the number of

lags of interest (i.e., -5 to +5 and 1 correlation at lag 0, total of 11 comparisons). Lagged results

for the target symptoms are presented in Figures 7 and 8. As Figure 7 illustrates, for number of



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Figure 7. Cross-correlational analyses showing direction of temporal relationship of change in numberof attacks with change in level of worry about panic during therapy*p .01. **p .001.

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

5 4 3 2 1 0 1 2 3 4 5

ExtentofInflue

nce

|r|

Direction and Timing of Influence

worry leads # of attacks # of attacks leads worry

**

****

* *

Figure 8. Cross-correlational analyses showing direction of temporal relationship of change in level of

worry about panic with change in avoidance behaviors during therapy*p .01. **p .001.

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

5 4 3 2 1 0 1 2 3 4 5

ExtentofIn

fluence

|r|

Direction and Timing of Influence

avoidance leads worry worry leads avoidance

**

*** ****** **

attacks and worry, significant cross-correlations were obtained at the 0, +1, +2, +4, and +5 lags,indicating that decreases in number of attacks preceded decreases in level of worry by 1, 2, 4, and

5 weeks. As Figure 8 illustrates, for worry and avoidance behavior, significant cross-correlations

were obtained at the +1,+2,+3, and +5 lags, indicating that decreases in worry preceded decreases

in avoidance behavior by 1, 2, 3, and 5 weeks. However, results also indicate significant correla-

tions at -1and -3 lags, suggesting that at these time points, decreases in avoidance behavior may

also precede decreases in worry about future panic attacks.

Visual examination of Figures 3 to 5 was used to determine which aspects of treatment pre-

ceded the dramatic decreases in number of attacks, worry about future panic attacks, and avoid-

ance behaviors. Examination suggests that the 6-week period of education about panic and



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Elkins and Moore 17

incorporation of coping skills (relaxation and cognitive skills) was effective for reducing the

patients number of panic attacks from five, experienced during baseline, to none, experienced

during these first three components of treatment. This information, combined with results of

cross-lagged correlations, suggests that education and coping skills led to a decrease in number

of attacks, which led to a decrease in worry about attacks and subsequent decrease in avoidancebehaviors. However, results from cross-lagged correlations for worry and avoidance behaviors

also suggest the presence of a possible reverse pattern, where reductions in avoidance behavior

may also fuel further decreases in worry about future attacks. In fact, this pattern is consistent

with Craske and Barlows (2007a) treatment conceptualization such that increases in participa-

tion in previously enjoyed activities may lead to increases in competency or feelings of control

about future panic symptoms.

8 Complicating Factors

Anthonys use of antidepressant and antianxiety medication throughout the course of treatment

may have contributed somewhat to the significant gains achieved during the period of psycho-

therapy intervention. However, Anthony reported decreased use of Xanax to manage anxiety

symptoms during the course of treatment and discontinuation of use entirely at termination and

all subsequent follow-up sessions. In addition, at the 9-month follow-up session, Anthonyreported that his psychiatrist was aiding him in a program to taper off his use of Effexor because

of a significant decrease in depressive symptoms following termination. It may be that the effect

of treatment to reduce panic symptoms, improve management of symptoms, and decrease avoid-

ance behavior led to improved self-efficacy to control panic and anticipatory worry, whichallowed Anthony to reduce coping strategies (medication) no longer perceived as necessary to

manage his anxiety.

A complicating factor related to the interpretation of the results is that although Anthonysavoidance behavior decreased over the course of treatment, the decrease did not meet statistical

significance after correcting for multiple comparisons. This result may be related to the pattern

of results for the treatment phase of the study. Specifically, two peaks in avoidance behavior

occurred during the latter portion of treatment (see Figure 5). This finding is not surprising from

a clinical perspective, as later treatment sessions involved interoceptive and in vivo practice of

exposure exercises defined in session. As exposure exercises involve facing physical sensations

and situations that have prompted panic symptoms in the past, such exposure can prompt a return

to avoidance behaviors in an attempt to decrease anxiety. Similar findings have been demon-

strated in theoretical and clinical literature (see Barlow & Craske, 1994; Craske & Barlow,

2007a, 2007b, for review). It is interesting to note that when these two peaks in avoidance behav-ior were removed from the data stream, we achieved statistical significance for level change

from baseline to treatment phases (R=-0.204,p= 0.0106), thus supporting our conjecture thattreatment gains had been achieved in this area, despite a temporary return of symptoms.

9 Managed Care Considerations

As health care costs in the United States continue to rise, the importance of determining cost

effective forms of mental health treatment steadily grows. The results of the current study sug-

gest that treatment of panic disorder with agoraphobia can be successfully conducted within

more complex clinical populations. In addition, CBT treatments for panic have been routinely

examined in community mental health and medical settings with positive results (Roy-Byrneet al., 2005; Wade, Treat, & Stuart, 1998) and are becoming more frequently utilized in these

settings with increased focus on providing behavioral health in primary care settings. Typical



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CBT approaches for panic disorder can be completed in as few as 12 sessions and can be modi-

fied to incorporate simultaneous pharmacological treatment if necessary. In addition, the patient

self-help manual can be used to enable the patient continue to process information and prac-

tice techniques between sessions, which may serve to facilitate a faster rate of change and

decrease the likelihood of attrition. Finally, CBT approaches for panic disorder do not requireextensive training in administration and can be tailored to meet the specific symptoms or com-

plicating factors of each patient (e.g., comorbid mental health problems, physical health prob-

lems, severity of symptoms; Craske & Barlow, 2007a).

10 Follow-Up

Following termination, Anthony was contacted for 1-month, 6-month, and 9-month follow-up

sessions during which the therapist and patient discussed maintenance of treatment gains, problem-solved areas of difficulty, and discussed new achievements made toward goals. During the 8th

month, Anthony contacted the therapist to discuss anxiety and depressive symptoms regarding a

trip his parents (primary support group) planned to take overseas. The therapist met briefly with

Anthony to process and validate his emotions, discuss coping strategies to manage symptoms

(e.g., journaling, maintaining routine, seeking other social support), and offer support and encour-

agement. As noted above, Anthony completed the OQ-45.2 at each follow-up session. Findingsdemonstrated a decrease in symptoms from treatment to follow-up sessions with a moderateeffect size (Cohens d= 1.53, r= 0.61).

Throughout the follow-up period, Anthony submitted periodic email updates regarding hisprogress. Information communicated in these updates indicated that he had not only maintained

treatment gains (no panic symptoms) but had also completed the life goal of accompanying his

father on a boating trip to Floridaa trip the two had not made together in the last 7 years because

of Anthonys symptoms. Thus, in addition to measurable improvements during the treatmentperiod, anecdotal evidence supports Anthonys continued progress toward his long-term goals.

At the final follow-up session 9 months post termination, Anthony provided a description ofthe most important parts of treatment that had aided his reduction of symptoms and maintenance

of treatment gains. Specific treatment mechanisms identified included an increased sense of

control as a result of improved coping skills and exposure practices which helped me to face

what I feared.

11 Treatment Implications of the Case

Overall, the results of the current study indicate that CBT was successful in the reduction ofpanic symptoms, worry, and avoidance behaviors for a client diagnosed with panic disorder with

agoraphobia, as well as reductions in other symptoms and behaviors not specifically targeted

during treatment. Specifically, Anthony reported a decrease in depressive symptoms (as mea-

sured by the daily mood record, completed during treatment; beginning of treatment = 4.2, ter-

mination = 1.6 on a scale from 0 to 8) as well as a decrease in smokeless tobacco use (from 2 cans

per day at baseline to less than half a can per day at termination). These findings suggest that

treatment of panic disorder in more complex clinical populations and potentially with complex

patients in other settings (medical, community mental health) may have the added benefit of

reducing comorbid mental health symptoms as well as negative health-related behaviors. In fact,

a simultaneous decrease in depressive symptomatology during the course of treatment for panic

disorder is supported by prior empirical literature (Barlow, Craske, Cerny, & Klosko, 1989;

Telch et al., 1993; Wade, Treat, & Stuart, 1998), although this has been less measured in ran-

domized controlled trials of treatment for panic disorder.



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Elkins and Moore 19

It is also important to highlight Anthonys lengthy medication treatment history for panic

symptoms. In medication treatment trials, Anthony might have been classified as treatment

resistant because of the continued presence of significant panic symptoms despite 10 years of

medication treatment. Yet, Anthony responded quite well to CBT treatment, which may bring

into question the validity of defining an individual as treatment resistant without participationin a CBT trial. This finding is consistent with other studies demonstrating remittance of panic

symptoms after CBT for individuals who responded poorly to medication treatments (e.g., Heldt

et al., 2003; Otto, Pollack, Penava, & Zucker, 1999; Pollack, Otto, Kaspi, Hammerness, &

Rosenbaum, 1994), as well as sustained benefit of these CBT effects well after discontinuation

of therapy (e.g., Heldt et al., 2006).

In addition to effectiveness of these components of treatment, it is also important to empha-

size the impact of Anthonys effortful participation in his treatment in reduction of symptoms

and maintenance of progress. In fact, Anthony attended all treatment and follow-up sessions andcompleted all in-session and between-session exercises without interruption, factors which arenot the experience of many clinicians. Although this study adds to the existing literature related

to treatment effectiveness, it would be important to test this treatment approach with single-casedesigns among those who have additional risk factors (e.g., comorbidity with other psychologi-

cal disorders, low income or other resources, low levels of support), to determine how this treat-

ment approach might impact outcome within these additional constraints.

An important clinical application indicated in the current study relates to the importance of

balancing a manualized approach to treatment with clinical flexibility. For example, although the

typical length of treatment identified by the Mastery of Your Anxiety and Panic manual is

between 12 and 15 treatment sessions and treatment length in the current study was 16 sessions

with four follow-up booster sessions, these additional booster sessions were important in

Anthonys sense of mastery (completed all exposure activities on hierarchy rather than just ini-

tial activities) and maintenance of treatment gains (follow-up sessions were used for review andproblem solving). Clinical flexibility may also be an important factor to consider when applying

this treatment to patients with comorbidity or significant barriers to treatment.

12 Recommendations to Clinicians and Students

Overall, the present case study builds on the existing empirical base supporting the use of

CBT in the treatment of panic disorder and provides an application of this approach using a

single-participant, time-series research design. This study provides important clinical indica-tions regarding the generalizability of this treatment approach for complex clinical popula-

tions and implies that future research should continue to examine this approach in clinicalpractice settings to determine important individual factors that may contribute to treatment

outcome.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interests with respect to the authorship and/or publication

of this article.

Funding

The author(s) received no financial support for the research and/or authorship of this article.

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Zaubler, T., & Katon, W. (1996). Panic disorder and medical comorbidity: A review of the medical and

psychiatric literature.Bulletin of the Menninger Clinic,60(2 Suppl. A), A12-A38.Zaubler, T., & Katon, W. (1998). Panic disorder in the general medical setting. Journal of Psychosomatic

Research,44, 25-42.

Bios

Sara R. Elkins, MA, is a doctoral student at the University of Tennessee. Her research interests focus on

internalizing and externalizing problems in childhood and adolescence, parenting practices, and treatment

outcome studies.

Todd M. Moore, PhD, is an assistant professor of psychology at the University of Tennessee. His research

interests and publications focus on intimate partner violence and addiction. He is particularly interested inresearch using handheld computers to examine the extent to which the immediate effects of alcohol lead to

partner violence, and to examine the effects of cravings and negative emotions on risk for relapse among

substance abusers.

Documents

A Time-Series Study of the Treatment of Panic Disorder