panic provocation procedures in the treatment of panic disorder: early perspectives and case studies

BEHAVIOR THERAPY 30, 305--317, 1999

Panic Provocation Procedures in the Treatment of Panic Disorder: Early Perspectives and Case Studies

STEFAN G. HOFMANN

LYNN E BUFKA

DAVID H. BARLOW

Boston University

Although panic provocation procedures have been utilized for many decades to gen- erate and test hypotheses about the pathophysiology of panic disorder, very little is known about the value of these procedures for treatment. In this article, we discuss the theoretical and practical issues related to panic provocation procedures in the treatment of panic disorder. We conclude that hyperventilation, physical exercise, and other activities that induce paniclike symptoms are among the most suitable provocation procedures for use in treatment. Two cases illustrate the use of such procedures in cognitive-behavioral intervention.

Dramatic physiological sensations are one of the key diagnostic criteria for panic disorder. Panic provocation procedures have been shown to produce intense and uncontrollable physical sensations by stressing certain neurobio- logical systems. These procedures are more likely to provoke panic attacks in panic patients than in patients with other disorders or in healthy controls (e.g., McNally, 1994). Investigators have been using panic provocation procedures in the laboratory for many decades with the goal of identifying the pathophysiological mechanism of panic disorder. Some of the most inten- sively studied laboratory panic provocation procedures are CO2 inhalation, hyperventilation, sodium lactate and bicarbonate infusions, cholecystokinin challenge, and caffeine ingestion.

One of the early studies that employed a panic provocation procedure in the laboratory was conducted by Wearn and Sturgis in 1919. The authors administered 5 mg of adrenaline intravenously to army recruits suffering from "irritable heart syndrome" and compared their response to a control group. After the infusion, patients reported typical panic symptoms, such as

We thank our anonymous reviewers for their helpful comments and suggestions. Address correspondence to Dr. Stefan G. Hofmann, The Center for Anxiety and Related Dis-

orders at Boston University, 648 Beacon Street, 6th floor, Boston, MA 02215. Tel: (617) 353- 9610; Fax: (617) 353-9609; e-mail: [email protected].

305 005-7894/99/0305-031751.00/0 Copyright 1999 by Association for Advancement of Behavior Therapy

All rights for reproduction in any form reserved.

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palpitations, dizziness, and tachycardia. Although the control subjects reported similar but less pronounced physiological symptoms, they reported much less anxiety than the patients. Numerous subsequent studies found a similar pattern of results with other provocation procedures (Breggin, 1964).

Although laboratory biological challenge tests, such as CO2 inhalation and lactate infusions, have been the most widely studied panic provocation procedures, panic attacks can also be induced through procedures that directly affect respiration or through behavioral methods, such as physical exercise (e.g., Barlow, 1988). The latter is closely related to the so-called "effort syndrome," which was one of the most popular names for panic disorder in the t940s (Barlow). The term "effort syndrome" was created by Lewis (1917) to describe soldiers from World War I who had problems tolerating the physical exertion when performing their army duty. During the period between World War I and II, this inability to engage in strenuous physical activity then be- came the most prominent sign of what is now known as "panic disorder." Shortly after World War II, Cohen and White (1947) conducted a series of studies using physical exercise as a panic provocation procedure. These studies found marked differences between panic patients and controls in their psychophysiological response during strenuous exercise (running on a tread- mill). Patients also terminated the exercise earlier than controls and they complained of numerous paniclike symptoms.

Panic Provocation Procedures in Treatment: Theoretical Issues Although panic provocation procedures have a long history, the pathophys-

iological mechanism of panic is still uncertain and controversial. After reviewing the literature, Barlow (1988) and McNally (1994) concluded that there is probably no single underlying biological mechanism of action that can account for all provocation procedures, and a number of competing explana- tions have been discussed, including biological (e.g., Ley, 1989; Klein, 1993; see Asnis and van Praag, 1995, for a review) and psychological mod- els. The cognitive model of panic, for example, suggests that panic attacks arise from catastrophic misinterpretations of physiological symptoms that are induced by the panic provocation procedures (e.g., Clark, 1986). Other theorists have suggested that physiological sensations induced by the provocation tests elicit fear after patients have learned to fear bodily symptoms ("fear of fear") through interoceptive classical conditioning of internal bodily sensations (Goldstein & Chambless, 1978). However, McNally (1990) has argued that the fear of fear in panic disorder is conceptually difficult to describe in terms of interoceptive conditioning because it is unclear how to identify and separate the conditioned stimulus from the conditioned response (cf. Forsyth & Eifert, 1996). Alternatively, the fear of bodily sensations might be a result of high anxiety sensitivity (Reiss & McNally, 1985), which refers to the person's belief that physiological arousal might lead to harmful consequences.

PANIC PROVOCATION IN TREATMENT 307

Probably the first experiment that used a biological challenge procedure as an anxiety reduction technique was conducted by Bonn, Harrison, and Rees (1971). The authors hypothesized that "anxiety states might be maintained by inadequate severity and quantity of fear attacks in neutral situations" (p. 469). Therefore, Bonn and colleagues assumed that repeated administration of a biological challenge procedure should lead to a gradual decrease in the patients' anxiety response. In their experiment, the investigators administered sodium lactate to 33 patients suffering from "intractable anxiety states without marked specific phobia" for 3 weeks twice-weekly. The results showed a significant drop in the patients' general anxiety level as measured by self- report instruments. The authors concluded: "We were impressed by the ob- servation that the phobophobic element, which was so frequently seen in our patients, was substantially reduced after treatment, leading to interruption of a pathogenic somato-psychic sequence which helped to maintain the anxiety neurosis" (p. 470).

Surprisingly, this exciting line of research has been largely ignored with the exception of a few studies (Beck & Shipherd, 1997; Beck, Shipherd, & Zebb, 1997; Griez & van den Hout, 1983, 1986; Rachman & Levitt, 1988; van Hout, Emmelkamp, & Scholing, 1994; van den Hout, van der Molen, Griez, Lousberg, & Nansen, 1987). These studies confirmed the findings by Bonn et al. (1971), but also showed that repeated trials of the same procedure do not lead to fear reduction in all individuals. For example, Beck and Shipherd (1997) administered two sessions of 12 repeated inhalation trials of 35% COz to 12 individuals with panic disorder. Following the methodology introduced by Rachman and Levitt (1988), individuals were classified into mutually exclusive groups based on the slope of their subjective anxiety response over the exposure trials. Half of the patients (n = 6) were classified as "habituators" because they showed decrements in anxiety from pre- to post-inhalation during both sessions with a more rapid decline during the sec- ond session. Five individuals were classified as "sensitizers" because they showed an increase in anxiety as a result of the repeated exposure trials. One subject was classified as "nonresponder" because neither a decrease nor an increase in anxiety was detected. Although all patients received the same stimulus, the nonhabituators seemed to evaluate the resulting physical sensations as being more intense. As discussed by the authors, these results are in line with studies on habituation and sensitization suggesting that repeated presentation of the same stimulus can lead to habituation or sensitization depending on the perceived intensity of the stimulus. If a stimulus is perceived as intense, it leads to sensitization and increased likelihood of responding to the stimulus, whereas a stimulus that is perceived as "weak" is more likely to result in habituation after repeated exposure to it (Kilnmel, 1973; Thompson, Groves, Tyler, & Roemer, 1973; van Olst, 1971).

In addition, Breggin (1964) noted that the perception of the situation seemed to moderate the patient's emotional response because a situation that appeared to be more "dangerous" (due to the presence of medical equipment

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and research staff in the experiment) elicited relatively greater anxiety in patients undergoing a panic provocation procedure. These findings are in line with more recent studies which showed that panic patients who were informed about the effects of CO2 inhalation reported less anxiety and fewer catastrophic thoughts than uninformed individuals (Rapee, Mattick, & Murell, 1986). Furthermore, nonanxious individuals who were told that lactate infusion would produce unpleasant bodily sensations experienced more anxiety than nonanxious subjects who were told that lactate would induce pleasant feelings (van der Molen, van den Hour, Vromen, Lousberg, & Griez, 1987). Moreover, panic patients who believed they had control over the amount of CO2 they inhaled by turning an inoperative dial were less likely to panic than individuals who knew that they had no control over it (Sanderson, Rapee, & Barlow, 1989). Similarly, panic patients who underwent a CO2 challenge were less anxious in the presence of their "safe person" than patients without their "safe person" present (Carter, Hollon, Carson, & Shel- ton, 1995). Finally, a study by Schmidt, Trakowski, and Staab (1997) suggested that cognitive behavioral treatment of panic disorder significantly reduces CO2-induced panic attacks.

In summary, the literature suggests that repeated trials of the same panic provocation procedure reduce panic-related fears in some individuals. Although the pathway of fear-reduction is not well understood (Beck et al., 1997), the fearful responding during the provocation procedure is probably a function of perceived stimulus intensity and other cognitive variables, such as perceived controllability of the stimulus.

Panic Provocation Procedures in Treatment: Practical Issues CO2 inhalation, lactate infusion, and other traditional laboratory biological

challenge tests are often impractical for clinicians to use in therapy. Such tests are costly and require sophisticated equipment or medical expertise. Furthermore, these procedures are often invasive and induce symptoms that are perceived as being too "strong," which could lead to an increase rather than a decrease in the fear responding.

In contrast, hyperventilation or physical exercise seem to be much better suited for use in treatment. These exercises, often referred to as "interocep- tire exposure practices," can be designed to elicit dusters of physical sensations that are very similar to the patients' panic attacks. For example, the therapist might create "mini" panic attacks in the office by having patients perform physical exercises to elevate their heart rate. Alternatively, patients may be asked to hyperventilate or breath through a thin straw to create smothering sensations. Patients are also assigned certain practices between sessions which include activities that precipitate the development of anxiety- provoking physiCal sensations (e.g., drinking caffeine and going to scary movies). In contrast to most other panic provocation procedures, such practices do not require any invasive medical procedures or complicated medical


equipment. Moreover, many of these practices are under the patient's direct control and are more likely to be perceived as "weak" (i.e., less intense and shorter lasting) symptoms. Therefore, these practices are less likely to "sensitize" patients (Beck & Shipherd, 1997; Beck et al., 1997; Rachman & Levitt, 1988) as compared to many laboratory panic provocation procedures.

Nevertheless, our experience has shown that not all patients benefit from these interoceptive exposure practices. Therefore, therapists might want to consider the following general guidelines concerning the use of panic provocation procedures in the treatment of panic disorder.

Prior to starting treatment, it is important to know whether patients exhibit any overt avoidance behaviors that may suggest an elevated fear of bodily sensations. Individuals who avoid activities and situations due to the physiological arousal associated with them are more likely to benefit from certain panic provocation procedures. Therefore, a thorough diagnostic assessment often provides some of the most valuable information for the subsequent treatment process. For example, as part of the Anxiety Disorders Interview Schedule (ADIS-IV-L; DiNardo, Brown, & Barlow, 1994), a structured diagnostic interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) lifetime diagnoses, patients are asked the question: "Have the attacks caused you to change your behavior/lifestyle in any way?" Individuals with a heightened level of fear of arousal symptoms often avoid situations and activities such as hot and stuffy areas (e.g., cars, stores), shopping malls, running up a flight of stairs, walking outside in intense heat or in very cold weather, aerobics, lifting heavy objects, dancing, watching horror movies, eating heavy meals, watching exciting movies or sports events, getting involved in "heated" debates, having a shower with the doors and windows closed, being in a sauna, hiking, sports, drinking coffee, eating chocolate, standing quickly from a sitting position, and getting angry (Barlow & Craske, 1994).

Additional information comes from standardized self-report questionnaires that measure fear of arousal symptoms. Two self-report instruments that measure fear of arousal symptoms often provide useful information: The 18-item BSQ (Chambless, Caputo, Bright, & Gallaher, 1984) and the 16-item Anxiety Sensitivity Index (ASI; Peterson & Reiss, 1987). The BSQ was developed to measure "fear of fear" by asking subjects to indicate the degree of fear of certain physical sensations, including heart palpitations, shortness of breath, and dizziness. Similarly, items of the ASI include, "It scares me when my heart beats rapidly," "It scares me when I feel short of breath," and "It scares me when I feel faint." Elevated scores on these measures further suggest that the subject might benefit from interoceptive exposure tests.

But even if a patient scores within the normal range in these self-report instruments or does not show any clear avoidance of activities and situations due to the physiological arousal associated with them, repeated interoceptive exposure practices can still be an effective anxiety-reducing treatment com- ponent. Therefore, therapists are advised to determine the patient's anxiety

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response during standardized interoceptive exposure tests as a standard procedure when treating panic disorder patients. For example, as part of the Panic Control Treatment (Barlow & Craske, 1994; Barlow, Craske, Cerny, & Klosko, 1989), patients are often asked to engage in a number of practices, including holding one's breath for 30 seconds, running in place for 1 minute, spinning in an office chair for 1 minute, hyperventilating for 1 minute, and breathing through a thin cocktail straw for 2 minutes. After each exercise, the therapist then explores any physical sensations that the patient experienced during the practice. Furthermore, the patient is asked to rate his or her anxiety and the similarity to naturally occurring panic attacks.

Some patients report high anxiety during exercises that predominantly induce an increase in heart rate (e.g., when hyperventilating or when running in place), whereas others are more fearful of exercises that predominantly induce feelings of breathlessness or smothering sensations (e.g., when holding one's breath or when breathing through a thin cocktail straw). Therefore, the therapist is advised to pay close attention to the patient's physiological response to these procedures when evaluating the fear response to these exercises. Physiological recordings can be a valuable source of information when used in addition to the patient's subjective report, which is often subject to distortion. A heart-rate monitor, for example, might show that the patient's subjective anxiety report is positively correlated with his or her heart-rate response during different interoceptive exposure tests, although the patient might not state that heart palpitations are particularly fear-provoking. This could then provide the therapist with useful information when designing the interoceptive exposure practices for a particular patient. Unfortunately, however, such data have rarely been considered in the diagnostic assessment and treatment of panic disorder. In the past, this might have been due to the high costs of physiological equipment and, possibly, the lack of technical expertise with these devices. However, recent technological advances make it now pos- sible to ambulatorily record a person's autonomic activity using low-cost and user-friendly monitoring devices (e.g., Hofmann & Barlow, 1996).

Practices that induce mild or moderate anxiety and physical sensations are most useful for the initial exposure sessions because panic patients are more likely to show a decrease in their anxiety response if the stimulus is perceived as "weak." In some cases, interoceptive exposure practices might have to be modified in order to gradually increase the intensity of the targeted symptom so that patients are able to develop tolerance at a lower level of intensity before further increasing the intensity to the targeted symptom. For example, a patient who fears dizziness might first be asked to roll or shake his or her head. Once the patient's anxiety has significantly declined after repeated trials of this exercise, the therapist may then ask the patient to walk in circles or to spin in an office chair for subsequent exposure practices. Similarly, the level of perceived controllability of a target symptom (e.g., heart palpitation) can gradually be reduced by first eliciting this symptom under structured conditions (e.g., running in place in the therapist's office) before eliciting the


symptom under less structured and more naturalistic conditions (e.g., drinking coffee).

Case Examples Two cases will illustrate the use of panic provocation procedures as part of

Panic Control Treatment (PCT), a structured 11-session cognitive-behavioral intervention for panic disorder (cf. Barlow & Craske, 1994; Barlow et al., 1989) that combines psychoeducation, cognitive therapy, and exposure techniques. During the initial sessions, patients are provided with psychoeduca- tional information regarding the nature of anxiety and panic attacks, and they are taught a breathing technique that focuses on strengthening diaphragmatic breathing to reduce the physical sensations associated with hyperventilation. Furthermore, cognitive restructuring techniques are applied to change catastrophic predictions typical of individuals with panic disorder. At week 6 of the PCT protocol, interoceptive exposure exercises are introduced, such as running in place, hyperventilating, and spinning in an office chair. After learning the exposure exercise in session, the patient is instructed to practice the exercise three times daily as part of the "homework" assignments. The patient is then assigned different exercises that evoke at least moderate anxiety to practice daily outside the therapy session. Once the patient has habituated to an exercise, a new exposure practice is introduced. In later sessions, more naturalistic panic provocation tests are assigned, including engaging in a vari- ety of avoided activities that precipitate the development of anxiety-provoking physical Sensations (e.g., drinking caffeine and going to scary movies).

The following two cases will illustrate the use of repeated interoceptive exposure exercises as part of treatment for panic disorder. Treatment was conducted by doctoral level psychologists who underwent special training in PCT. Shortly before and after the intervention, the clients were interviewed by independent and experienced clinicians using the ADIS-IV-L. Further- more, clients were asked to fill out the ASI.

Case 1

The patient was a 30-year old white female who met DSM-IV criteria for Panic Disorder with Agoraphobia with an additional diagnosis of Anxiety Disorder Not Otherwise Specified (NOS). At the onset of treatment, her panic was moderate and agoraphobic avoidance was mild. However, she occasion- ally avoided elevators and being at home alone due to the fear of panic and associated physical sensations. She also had mild to moderate anxiety associated with interstate driving, air travel, and tunnels. Her ASI score of 34 at pretreatment suggested strong sensitivity to the physical sensations of anxiety.

After the patient performed the initial interoceptive exposure tests during the sixth treatment session, the therapist decided to instruct the patient to practice breathing through a thin cocktail straw first because it elicited a mod-

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erate level of anxiety and moderately intense physical sensations. The patient was asked to practice three consecutive trials of the exercise each day as part of her daily homework assignment between sessions 6 and 7 and to record her level of anxiety and the intensity of her bodily sensations during each trial on a scale from 0 (not at all) to 8 (extreme).

Figure 1 shows her anxiety ratings and intensity ratings of her bodily sensations after each trial of breathing through a thin straw. The patient practiced the homework irregularly but did perform three trials each day for a total of 8 days. Breathing through a thin straw initially evoked moderate anxiety and she appeared to first sensitize to the experience. At the fifth day of practice, her anxiety finally declined with repeated exposure trials. Although the patient was instructed to conduct each exposure trial in the same way, she reported less intense physical sensations as her anxiety decreased. This might have been related to the common difficulty among panic patients to distin- guish between intensity of bodily sensations and intensity of anxiety.

After the patient habituated to this first exercise, the therapist instructed the patient to practice spinning in a chair and hyperventilating after sessions 8 and 10, respectively. As treatment progressed, her ASI score dropped to 25, the moderate range of reactivity to the physical sensations of anxiety. At the posttreatment assessment, her diagnosis of Panic Disorder with Agoraphobia was in partial remission, and her ASI score had dropped slightly to 22. She

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FIG. 1. Subjective ratings of anxiety and intensity of bodily sensations after repeated trials of breathing through a thin straw.


still had occasional panic attacks but less panic-related fear and avoidance. She did still avoid driving, especially at night, but was not avoiding any other situations. Furthermore, she no longer met diagnostic criteria for Anxiety Disorder NOS at the posttreatment assessment.

Case 2

The patient was a 25-year-old white female who met DSM-IV criteria for Panic Disorder with Agoraphobia (mild agoraphobia and panic) and Anxiety Disorder NOS. She exhibited moderate avoidance of flying, drinking caffeine, traveling far from home, saunas, and hot and stuffy rooms. Her ASI score of 25 at pretreatment indicated moderate sensitivity to the physical sensations of anxiety.

During the initial interoceptive exposure tests the patient reported moderately intense sensations when running in place for 1 minute and holding her breath for 30 seconds. Most of the other exercises induced very intense physical sensations. For example, spinning in an office chair for 1 minute induced intense sensations of dizziness and lightheadedness (subjective rating of 8) and a moderate to high level of anxiety (subjective rating of 6).

The therapist initially instructed the patient to repeatedly practice running in place for 1 minute (as a homework assignment between session 6 and 7), and then holding her breath for 30 seconds (as a homework assignment between session 7 and 8). Once the patient habituated to these exercises, the therapist then asked the patient to practice spinning in an office chair for 1 minute as a homework assignment between session 9 and 10. As with the pre- vious exercises, the patient was asked to practice three consecutive trials of this exercise daily, and to record her level of anxiety and the intensity of her bodily sensations during each trial on a monitoring sheet.

Figure 2 shows her anxiety ratings and intensity ratings of her bodily sensations after each trial. The patient performed at least two consecutive trials of this exercise for 11 days. Spinning in the chair initially evoked moderate to high anxiety which declined with repeated exposure practices. Her ASI score dropped from 25 to 10 at posttreatment, indicating a mild sensitivity to the physical sensations of anxiety. At the posttreatment assessment, both anxiety disorder diagnoses were no longer clinically significant and were classified as "in partial remission;' She no longer avoided any situations except for some mild avoidance of situations that caused her to feel excited, and she reported only mild fear of driving and moderate fear of flying.

Summary and Conclusion Panic provocation procedures induce potentially fear-provoking bodily

sensations and panic attacks in some people. Although such procedures have been used for many years by anxiety researchers to study the biological mechanism of panic attacks, we know little about their value for the treatment of panic disorder. Recent research shows that repeated trials of some panic

314 HOFMANN ET AL.

Case 2: Spinning in Chair

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FIG. 2. Subjective ratings of anxiety and intensity of bodily sensations after repeated trials of spinning in an office chair.

provocation procedures can lead to a decrease in anxiety in some individuals with panic disorder. Although the mechanism of anxiety reduction is not well understood, it seems that it is more likely to occur if the stimulus is initially perceived as "weak" and if exposure to the stimulus leads to a greater degree of perceived emotional controllability (e.g., Eifert, Coburn, & Seville, 1992).

Interoceptive exposure exercises, such as hyperventilating, breathing through a thin cocktail straw, or spinning in a chair, seem to be particularly useful challenge tests for the treatment of panic disorder because they induce moderate and controllable sensations. Although little is known about the relative importance of such interoceptive exposure exercises for the treatment of panic disorder, they have become a critical part of most cognitive-behavioral treatment protocols (e.g., Barlow & Craske, 1994; Barlow et al., 1989).

We reported the effects of interoceptive exposure exercises (breathing through a thin cocktail straw and spinning in a chair) on subjective anxiety ratings in two case examples. Both cases showed a gradual decline in their anxiety response to the exercises over time. However, they differed in the type and intensity of the target symptom and the changes in anxiety response with repeated practices. Based on our experience, these two cases are typical examples and they illustrate the individual differences between patients and their responses to the interoceptive exposure practices.


Despite the differences, both cases no longer met diagnostic criteria for panic disorder by the end of treatment. It is uncertain what the relative contri- bution of the interoceptive exposure exercises for treatment response is because we did not isolate and systematically control this variable. However, the results of the two case examples are consistent with the findings from recent studies showing that repeated panic provocation procedures can significantly reduce panic-related anxiety in some patients (Beck & Shipherd, 1997; Beck et al., 1997). Furthermore, a meta-analysis on 43 studies compar- ing the efficacy of various panic disorder treatments (pharmacological treatments, cognitive-behavioral treatments without interoceptive exposure exercises, cognitive-behavioral treatments with interoceptive exposure exercises, and combined pharmacological and cognitive-behavioral treatments) found that treatments that combined cognitive-behavioral treatments with interoceptive exposure exercises yielded the strongest effect sizes (Gould, Otto, & Pollack, 1995).

In summary, we conclude that interoceptive exposure practices (e.g., hyperventilation, breathing through a thin straw, or spinning in a chair) are potentially useful and therapeutically effective components of cognitive- behavioral treatment of panic disorder. More studies are needed to systematically evaluate the therapeutic efficacy of interoceptive exposure exercises, to clarify the mechanism of action, and to explore the reason why such practices are beneficial for some patients but not for others.

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panic provocation procedures in the treatment of panic disorder: early perspectives and case studies

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