In 1988, Barlow examined the evidence from around the world and concluded that “with specifically targeted psychological treatments, panic is eliminated in close to 100% of all cases, and these results are maintained at follow-ups of over 1 year. If these results are confirmed by additional research and replication, it will be one of the most important and exciting developments in the history of psychotherapy”. The question facing researchers and clinicians alike is, with the benefit of more than a decade of subsequent research and replication, “Is it possible to concur with Barlow’s statement?”. The place to begin this evaluation is by addressing the criteria of effective treatment for panic disorder and agoraphobia.
Aims of treatment
Panic disorder and agoraphobia are currently conceptualized as two separate, but frequently related, disorders. Specifically, panic attacks are considered the “motor” that “drives” the agoraphobic avoidance. Therefore, it would be expected that effective long-term treatment for agoraphobia would require effective long-term management of panic attacks. By extension, the first aim of an effective treatment for agoraphobia (with panic disorder) would be to stop panic attacks and their interference in an individual’s life. The second aim would be to reduce any concurrent agoraphobic avoidance. Just as with the specific phobias, avoidance will involve anticipatory anxiety and anxiety triggered upon exposure and treatment will be more than simply “turning off’ avoidance. However, an ideal treatment would do more than modify the existing symptoms; it would reduce the vulnerability to the disorder. If the vulnerability to panic disorder and agoraphobia (e.g., trait anxiety) could be modified, relapse would presumably be decreased. In summary, effective treatment of panic disorder and agoraphobia will involve (1) the control of panic attacks, (2) the cessation of fear-driven avoidance, and (3) reduction of the vulnerability.
Combining drug and nondrug treatments
Examining the effects of combining treatments is not simple. Any grouping runs the risk of combining dissimilar categories (e.g., different drugs within one class, different dosages, different durations of administration, different forms of exposure, different cognitive interventions). The interested reader is referred to recent reviews by Spiegel and Bruce (1997) and Schmidt (1999) for more detailed discussions. For present purposes, the two main classes of drug that have been combined with behavioral treatments are the high-potency benzodiazepines and the tricyclic antidepressants. Van Balkom et al. (1997) conducted a meta-analysis on the combination of pharmacological and cognitive behavioral treatments of panic disorder with and without agoraphobia. Focusing on their indices of panic and agoraphobia, they concluded that among these studies high potency benzodiazepines, antidepressants, and cognitive behavioral treatments were all equally superior to a control and the gains were maintained following the termination of treatment. Interestingly, while in vivo exposure was no more effective than the control condition in alleviating panic symptoms, it was markedly effective in alleviating agoraphobic symptoms. Further, the effects of in vivo exposure were dramatically increased (effect size (Cohen’s d) = 2.47) by the addition of tricyclic antidepressants. This effect clearly warrants further investigation (especially because Fava et al. (1997) found that supplementing exposure with imipramine reduced the efficacy of in vivo exposure), but some light maybe shed on it by the work of Murphy et al. (1998). They found that patients with panic disorder and agoraphobia who were also depressed exhibited a reduction in the benefit derived from in vivo exposure sessions. Thus, given the potential mediating role of depression, antidepressants may enhance the efficacy of in vivo exposure by removing the otherwise inhibiting effects of depression. Continuing this speculation, similar increases in outcome may also be achieved by using the skills the client has acquired in cognitive behavioral therapy to focus on the symptoms of depression when these are comorbid with the anxiety disorder.
Considering the combination of psychological treatment with benzodiazepines, the picture seems less favorable. For instance, Schmidt (1999) concluded that the combination of cognitive behavioral therapy and benzodiazepines appears to produce poorer end-state functioning than cognitive behavioral therapy alone. Wade et al. (1998) found that the only predictor of posttreatment panic was pretreatment anxiolytic medication use, which they noted was primarily benzodiazepines. Further, if nonhuman data are considered, Bouton et al. (1990) found a dose-dependent interference with fear extinction in rats from two benzodiazepines. Thus these animal data suggested that relapse rates may be elevated when behavior therapies are combined with increasingly more potent benzodiazepines. Although the appropriate human studies have not been conducted, it is apparent that there is presently strong support neither for nor against combining benzodiazepines with cognitive behavioral therapy. Thus a reasonable position would seem to be that combining benzodiazepines with cognitive behavioral therapies should await research support before being recommended as routine clinical practice.
The treatment of panic disorder with agoraphobia is consistent with the etiology models discussed. A comprehensive nondrug treatment package involves panic control (e.g., education about anxiety, breathing retraining, panic provocation exercises) as well as modification of the agoraphobic avoidance and catastrophic misinterpretations (in vivo exposure and cognitive restructuring). Drug treatments, using high-potency benzodiazepines or the tricyclics, have been found to yield similar rates of treatment success probably because they also decrease anxiety and thereby facilitate exposure. However, while drug and nondrug treatments are both effective, there is one added bonus that is often not mentioned. There is evidence that cognitive behavioral therapy modifies the vulnerability factors that give rise to the disorder. For instance, Andrews and Moran (1988) found that an earlier version of the Clinician Guide and Patient Manual substantially reduced neuroti-cism scores and that the size of the decrease was predictive of subsequent relapse. Given the long-term advantages of reducing vulnerability, a cognitive behavioral intervention should probably be the treatment of choice.
Yet, despite the success of cognitive behavioral therapies for panic disorder and agoraphobia, there are two words of caution. First, surveys of clients serve as a salutary reminder of state of clinical practice. In a survey of 100 patients with panic disorder and agoraphobia, Bandelow et al. (1995) found that unproven treatments (e.g., herbal preparations) were overutilized and treatments with demonstrated efficacy (e.g., cognitive behavioral therapy and tricyclic antidepressants) were underutilized. Further, Wade et al. (1998) noted that clinicians are often ambivalent about using a structured, short-term treatment that requires adherence to a protocol, preferring to revert to more familiar approaches of selecting treatments that they believe will be effective for this particular patient. Therefore, it is not only important that the outcomes of research be disseminated, it is important that clinicians routinely use (and be encouraged by their management structures to continue to use) established and efficacious treatments.
A closing word of caution can be taken from more recent work of Barlow (1997). The present chapter opened with Barlow’s enthusiasm for this form of treatment, and he quite reasonably persists with this enthusiasm, commenting that “cognitive-behavioral treatments yielded the highest mean effect sizes [comparing] favorably with pharmacologic as well as combination drug and cognitive behavioral therapy treatments”. However, his enthusiasm is now tempered by data indicating that not insignificant numbers of patients continue to suffer from panic continuously or continually following treatment. For instance, Barlow described data from his group indicating that “while 74% of our patients remained panic free at a 24-month follow-up when followed cross-sectionally and 57% had reached a state of ‘high end-state functioning’ that would represent a state close to ‘cured,’ these numbers dropped notably when patients were followed longitudinally… Thus, it seems that at least some of these patients do reasonably well over the long term but continue to suffer from periods of exacerbation of their Panic Disorder and Agoraphobia”. Therefore, attention needs to continue to be allocated to those people who are less successful during therapy and identify how treatment can be delivered or targeted more effectively.