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A Time-Series Study of the Treatment of Panic Disorder

Sara R. Elkins and Todd M. Moore Clinical Case Studies 2011 10: 3 originally published online 6 December 2010 DOI: 10.1177/1534650110391901 The online version of this article can be found at: http://ccs.sagepub.com/content/10/1/3

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A Time-Series Study of the Treatment of Panic Disorder

Sara R. Elkins1 and Todd M. Moore1

Clinical Case Studies 10(1) 322 The Author(s) 2011 Reprints and permission: http://www. sagepub.com/journalsPermissions.nav DOI: 10.1177/1534650110391901 http://ccs.sagepub.com

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 employed a 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 treatment protocol, the patient demonstrated significant decreases in self-reported distress, anxiety and panic symptoms, and worry about having a panic attack. Several qualitative changes were also notable following termination, including decreased tobacco and psychiatric medication usage as well as decreased comorbid depressive symptoms and agoraphobia behaviors. Outcomes were 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 approximately 2.7% 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 behavior (Weissman, Klerman, Markowitz, & Ouellette, 1989); and greater use of medical and psychiatric resources than individuals without panic disorder (Zaubler & Katon, 1998). Contemporary cognitive-behavioral approaches treat panic disorder using a number of specific 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
1

University of Tennessee, Knoxville, TN

Corresponding Author: Sara R. Elkins, University of Tennessee, Department of Psychology, Austin Peay Building, Knoxville, TN 37996 Email: ssmith74@utk.edu

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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 efficacy, 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 demonstrated 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 of individuals 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 benzodiazepines (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 clinic attendance) but excluded from participation in many randomized controlled trials of CBT for panic disorder. The effectiveness study method, therefore, adds the additional step of determining 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 approach in 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 anxiety, 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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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, and 9 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 cost effectiveness 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 White male 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 urination 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 safe place. 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 shopping 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 programs (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 prevent 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 that his 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 lifelong romantic 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, feeling 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 pinpoint 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 frightening 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 returned with 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 Anthony reported 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 individuals 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 indicated a family history of panic attacks (brother) and a high frequency and severity of panic symptoms (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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In addition to the above-listed, research-based measure, Anthony was administered the Minnesota Multiphasic Personality Inventory2 (MMPI-2) as well as the Anxiety Disorders Interview 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 of mental 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 pathology and personality dimensions, and yields validity, clinical, and content scales. The MMPI-2 is considered 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 psychasthenia (Pt, T-score = 57), indicating a profile with the following descriptors: overcontrolled, tense, anxious, passive, ingratiating, somatization. This profile suggests a moderate anxiety disorder 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 within this scale. The ADIS-IV (Di Nardo, Brown, & Barlow, 1994) is a structured clinical interview designed to evaluate the presence of anxiety disorders and allow differential diagnosis among anxiety disorders, based on Diagnostic 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 of DSM-IV anxiety 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 the DSM-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, sweating, 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) unexpected 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 situations 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 support 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 met criteria for the following diagnostic conditions:
Diagnostic code Axis I Axis II Axis III Axis IV Axis V 300.21 305.10 V71.09 Diagnostic category Panic disorder with agoraphobia Nicotine dependence None Elevated blood pressure Occupational stressors Current: 50 Highest past year: 65

GAF

It was therefore recommended that Anthony begin individual cognitive behavioral psychotherapy 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 indicated 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 psychological perspective, the initial panic attack is viewed from a stress-diathesis model, such that the first 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 physiological 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 reinforcing 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 fastacting 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, treatment phase, and follow-up phase to test whether treatment gains were maintained.

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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 a 45-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. Individual items measure symptom status across a wide variety of disorders and assess personal and social 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 complete 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 the DSM-IV-TR criteria for panic disorder with 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 the treatment phase, which lasted 16 sessions. Anthony returned the daily rating sheets when he came to the weekly therapy session. The OQ-45.2 was administered monthly during the treatment 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 to observations 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-established, evidence-based treatment approach that typically yields high panic-free rates at termination and 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., physical sensations, thoughts, and behavior) and the difference between symptoms of panic and symptoms 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 overbreathing and its relation to panic symptoms were discussed. The process of slowed diaphragmatic breathing utilizing a one-in-relax-out procedure as well as attention to the breaths was demonstrated 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 muscle group 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 decatastrophizing 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, the therapist 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 planning 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 inductions based on similarity to those in a real panic attack and amount of anxiety these symptoms produced. 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 reported that 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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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-session practices. 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 graduated trials 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 exercises 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, particularly during symptom induction or in vivo exposure exercises. In addition to interoceptive exercises, Anthony was also trained in exposure to feared agoraphobia 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 practices. 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 discussion 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 activities. Long-term life goals identified included go on a boating trip to Florida; make my business 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 program for short time-series data streams. SMA employs a bootstrapping methodology that enables analysis 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 statistics, Pearsons correlations, and level change statistics for baseline and treatment phases. Autocorrelation 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 indicating 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 treatment 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 Bonferroni 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 significant 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 visually 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) M Overall distress Average anxiety Average worry about having a panic attack Number of panic attacks Avoidance behaviors 4.56 4.94 8.75 0.31 0.25 SD 1.97 2.25 0.66 0.68 0.43

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Treatment (n = 140) M 2.65 2.57 2.64 0.02 0.08 SD 1.63 1.86 2.24 0.19 0.27

Overall (N = 156) r p .0001 .0001 .0001 .006 .03

-.329 -.353 -.655 -.299 -.176

9 8 7 6 5 4 3 2 1 0

II

III

IV

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 measure 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 using the 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 followup 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 baseline to treatment (Cohens d = 3.10, r = 0.84) and a moderate effect size from treatment to followup phases (Cohens d = 1.53, r = 0.61).

Overall Distress

I. Education II. Relaxation III. Cognitive Skills IV. Exposure-Interoceptive V. Exposure-In Vivo

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9 8 7 Average Anxiety 6 5 4 3 2 1 0

II

III

IV

I. Education II. Relaxation III. Cognitive Skills IV. Exposure-Interoceptive V. Exposure-In Vivo

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

9 8 Worry About Having a Panic Attack 7 6 5 4 3 2 1 0

II

III

IV

I. Education II. Relaxation III. Cognitive Skills IV. Exposure-Interoceptive V. Exposure-In Vivo

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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II III

IV

Number of Panic Attacks

I. Education II. Relaxation III. Cognitive Skills IV. Exposure-Interoceptive V. Exposure-In Vivo

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

I 1

II III

IV

Avoidance Behaviors

I. Education II. Relaxation III. Cognitive Skills IV. Exposure -Interoceptive V. Exposure -In Vivo

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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Table 2. Autocorrelations and Level Change From Baseline to Treatment Phases
Baseline (n = 16) Autocorrelation (Lag-1) Overall distress Average anxiety Average worry about having a panic attack Number of panic attacks Avoidance behaviors .213 .238 .086 .148 .022 p .288 .103 .368 .351 .619 Treatment (n = 140) Autocorrelation (Lag-1) .611 .536 .637 .395 .212 p .0001 .0001 .0001 .0040 .011 Overall (N = 156) Autocorrelation (Lag-1) .549 .556 .793 .125 .189 Level change R .329 .353 .655 .299 .176

15

p .0001 .0001 .0001 .0510 .008

p .0002 .0006 .0001 .0001 .0226

70 60 50 OQ-45 Total Score 40 30 20 10 0

II

I. Start of Treatment Period II. Start of Follow-Up Period

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

slope), and as such, level of worry about having a panic attack was cross-correlated with both number 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-correlated with 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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0.4

Extent of Influence |r|

0.35 0.3 0.25 0.2 0.15 0.1 0.05 0 5 4 3 2 1

worry leads # of attacks

** ** ** * *

# of attacks leads worry

Direction and Timing of Influence

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

0.35

Extent of Influence |r|

0.3 0.25 0.2 0.15 0.1 0.05 0

* ** ** ** **

**

5 4 3 2 1
avoidance leads worry

worry leads avoidance

Direction and Timing of Influence

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.

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 correlations 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 preceded the dramatic decreases in number of attacks, worry about future panic attacks, and avoidance behaviors. Examination suggests that the 6-week period of education about panic and

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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 avoidance behaviors. 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 participation 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 psychotherapy 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, Anthony reported 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 avoidance behavior led to improved self-efficacy to control panic and anticipatory worry, which allowed 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 Anthonys avoidance 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 demonstrated 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 behavior 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 that treatment 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 suggest 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-Byrne et 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 modified 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 practice 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 require extensive training in administration and can be tailored to meet the specific symptoms or complicating factors of each patient (e.g., comorbid mental health problems, physical health problems, 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, problemsolved 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 encouragement. As noted above, Anthony completed the OQ-45.2 at each follow-up session. Findings demonstrated a decrease in symptoms from treatment to follow-up sessions with a moderate effect size (Cohens d = 1.53, r = 0.61). Throughout the follow-up period, Anthony submitted periodic email updates regarding his progress. 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 treatment period, 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 of the 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 of panic 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 measured by the daily mood record, completed during treatment; beginning of treatment = 4.2, termination = 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 randomized controlled trials of treatment for panic disorder.

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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 participation in 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 emphasize 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 and completed all in-session and between-session exercises without interruption, factors which are not 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-case designs among those who have additional risk factors (e.g., comorbidity with other psychological disorders, low income or other resources, low levels of support), to determine how this treatment 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 initial activities) and maintenance of treatment gains (follow-up sessions were used for review and problem 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 indications regarding the generalizability of this treatment approach for complex clinical populations and implies that future research should continue to examine this approach in clinical practice 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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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 in research 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.

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