Psychological Medicine, Page 1 of 10. f 2007 Cambridge University Press doi:10.1017/S0033291707000670 Printed in the United Kingdom

Prognostic indices with brief and standard CBT for panic disorder : I. Predictors of outcome M I C H A E L G. T. D O W 1 *, J U S T I N A. K E N A R D Y 2 , D E R E K W. J O H N S T O N 3, M I C H E L L E G. N E W M A N 4, C. B A R R T A Y L O R 5 A N D A I L E E N T H O M S O N 6 1

NHS Fife, Department of Clinical Psychology, Stratheden Hospital, Cupar, Fife, UK; 2 Centre for National Research on Disability and Rehabilitation Medicine, and School of Psychology, University of Queensland, Brisbane, Queensland, Australia ; 3 Department of Psychology, Kings College, University of Aberdeen, UK; 4 Department of Psychology, Pennsylvania State University, PA, USA; 5 Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Stanford, CA, USA ; 6 Health Psychology Department, Gloucestershire Royal Hospital, Gloucester, UK

ABSTRACT Background. Although the effectiveness of cognitive behavioural therapy (CBT) in the management of panic disorder (PD) is now well established, there have been few studies of predictors of outcome with this patient group using clinical effectiveness trial data, a hypothesis-testing model, and a dependent measure of clinically significant change. Method. The data for this study came from a randomized controlled trial of three forms of CBT delivery for PD with and without agoraphobia (two 6-week CBT programmes, one of which was computer assisted, and one therapist-directed 12-week CBT programme), comprising a total of 186 patients across two sites. Based on previous related research, five hypothesized predictors of posttreatment and follow-up outcome were identified and examined, using a series of bivariate and multivariate analyses. Results. The results in general supported the hypotheses. Strength of blood/injury fears, age of initial onset of panic symptoms, co-morbid social anxieties and degree of agoraphobic avoidance were predictive of both measures of post-treatment outcome. Degree of residual social difficulties and the continued use of anxiolytics at post-treatment were also shown to predict poor outcome at the 6-month follow-up. However, strength of continuing dysfunctional agoraphobic cognitions by the end of active treatment did not predict outcome at follow-up for the sample as a whole. Conclusions. The identification of consistent predictors of outcome with CBT has many clinical and research benefits. As CBT, however, is being delivered increasingly in a variety of brief formats, further research is required to identify moderators of response to these ‘non-standard’ treatment formats. and duration of panic episodes and self-rated anxiety have been shown to be predictive of post-treatment or follow-up outcome in some studies (Ronalds et al. 1997; Scheibe & Albus, 1997; Sharp & Power, 1999), but not others (e.g. Keijsers et al. 1994; O’Rourke et al. 1996 ; Katschnig & Amering, 1998). A higher degree of consistency has been reported for psychological co-morbidity as a negative correlate of outcome (Liebowitz, 1997 ; Lecrubier, 1998), including severity of associated agoraphobic avoidance

INTRODUCTION Despite significant recent advances in the use of cognitive behavioural treatment of panic disorder (PD), research has failed to identify consistent prognostic indices (Keijsers et al. 1994; Steketee & Shapiro, 1995). Baseline frequency * Address for correspondence: Dr Michael G. T. Dow, Department of Psychology, University of Stirling, Stirling FK9 4LA, UK. (Email : [email protected])

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(Hafner & Ross, 1983; Mavissakalian & Michelson, 1986; Fischer et al. 1988 ; Emmelkamp et al. 1992 ; Steketee & Shapiro, 1995 ; Liebowitz, 1997 ; Scheibe & Albus, 1997 ; Sharp & Power, 1999; Shinoda et al. 1999; Ramnero¨ & O¨st, 2004) ; co-morbid generalized anxiety disorder (Scheibe & Albus, 1997) ; concomitant depression (Keijsers et al. 1994 ; Ronalds et al. 1997 ; Sharp & Power, 1999; Fava et al. 2001) ; marital dissatisfaction (Dewey & Hunsley, 1990 ; Emmelkamp & Gerlsma, 1994) ; and personality disorder (Keijsers et al. 1994 ; Liebowitz, 1997 ; Shinoda et al. 1999). Low motivation for treatment and expectation of improvement (Keijsers et al. 1994; Clark et al. 1999), dysfunctional interpretations about bodily sensations and agoraphobic cognitions (Clark et al. 1994, 1999 ; Schmidt et al. 1997 ; Norton et al. 1999) have also been shown to predict poorer outcome. Sociodemographic variables have the weakest relationship with outcome (Keijsers et al. 1994; O’Rourke et al. 1996 ; McCusker et al. 2000). In terms of post-treatment prediction of long-term outcome, several variables have been shown to be significant, including degree of residual anxiety and agoraphobic avoidance (Fava et al. 2001) and the persistence of key dysfunctional cognitions, particularly the misattribution of bodily sensations (Clark et al. 1994, 1999). Such findings mirror similar relationships between post-treatment residual symptoms and sustained improvement in the management of mood disorders (Fava, 1999) and phobic states (O’Sullivan & Marks, 1990). Concomitant drug treatment at the time of remission of anxiety with cognitive behavioural therapy (CBT) has also been associated with higher rates of relapse compared to CBT alone (Marks et al. 1993; Brown & Barlow, 1995; Van Balkom et al. 1996; Otto et al. 1996; Fava et al. 2001), although Oei et al. (1997) failed to obtain similar findings. There are numerous reasons for such inconsistencies, including cross-study differences among measures of both predictor and outcome variables ; sample specific, non-replicable findings due to variable subject entry criteria ; and inadequate sample size for the number of postulated prognostic variables (Steketee & Chambless, 1992; Keijsers et al. 1994; Durham et al. 1997; Sharp & Power, 1999). Moreover,

the collective influence of multiple variables on outcome and their differential relationship to specific treatments have not, in general, been adequately investigated. In addition, much research in this area, as observed by Steketee & Chambless (1992), has involved a ‘haphazard approach to prediction ’, unguided by specific hypotheses, and based on clinical trials and outcome measures of limited ecological validity. The aim of the present study was to address such difficulties using data from a recent clinical effectiveness trial conducted by Kenardy et al. (2003 a), in which three forms of CBT delivery for patients with PD and PD and agoraphobia (PDA) were compared. Patients were randomly allocated to (a) ‘standard ’ 12-session therapistdirected CBT (CBT12); (b) six sessions of therapist-delivered CBT (CBT6) ; (c) six sessions of computer-assisted CBT (CBT6-CA) ; or (d) a waiting-list control condition. The results showed all three treatments to be effective, with CBT12 being significantly superior to CBT6 on a composite panic/anxiety measure at posttreatment. Outcome with CBT6-CA occupied an intermediate position between standard (CBT12) and brief (CBT6) therapist-directed treatments, but was not significantly different from either. A higher degree of variability of response to CBT6 compared to the standard approach was apparent on most measures. No differences were found between the active treatments at follow-up. The trial’s design provided an opportunity not only to examine in more detail factors predictive of outcome generally with CBT for PD but also to help identify moderators of outcome in relation to brief and standard forms of CBT with this patient group. This report and the subsequent one are concerned with each of these aims respectively. Hypotheses On the basis of the previous research, we hypothesized that : (a) baseline level of severity of panic disorder and associated anxiety, as determined by panic frequency and severity of panicrelated distress, duration of disorder, degree of agoraphobic avoidance and expectations about the likely effectiveness of therapy, will predict post-treatment outcome ;

Prognostic indices with CBT for PD : predictors of outcome

(b) baseline level of secondary associated disability, as determined by degree of comorbidity and impairment of social, occupational and family life, will predict posttreatment outcome ; (c) the degree to which patients retain, at the end of active treatment, dysfunctional cognitions involving the catastrophic misinterpretation of bodily sensations will predict outcome at follow-up ; (d) the degree of residual panic/anxiety symptoms and agoraphobic avoidance at the end of active treatment will also predict outcome at follow-up ; (e) the continuing use of anxiolytics, and in particular benzodiazepines, on completion of CBT will predict the maintenance of treatment gains at follow-up.

METHOD Data for the present study were derived from a randomized controlled trial of three forms of CBT delivery for PD with and without agoraphobia, the results of which, summarized above, have been reported fully elsewhere (Kenardy et al. 2003a). Treatments Therapy was conducted by registered clinical psychologists, all of whom had extensive CBT experience. The two brief forms of CBT delivery involved six 1-hour weekly sessions and were identical condensed versions of the standard format comprising 12r 1-hour weekly sessions. Detailed treatment protocols were prepared based on now well-established cognitive and behavioural theories of panic and its treatment (Clark, 1986 ; Barlow & Craske, 2000). CBT6CA involved the adjunctive use of a palmtop computer to prompt and encourage practice of the main cognitive and behavioural elements of treatment. Sample The sample comprised 186 patients with PD and PDA, recruited from two sites (Australia and Scotland), who were randomly allocated to 12 sessions of therapist-delivered CBT (CBT12), six sessions of therapist-delivered CBT (CBT6), computer-assisted CBT (CBT6-CA) or a

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waiting-list control condition. Full details of the entry criteria are described in the original outcome study report (Kenardy et al. 2003a). In summary, the sample comprised patients meeting DSM-IV (APA, 1994) criteria for PD, with or without agoraphobia ; had a current episode duration of at least 3 months ; were between 18 and 60 years of age; considered panic their main problem ; and had no depressive disorder severe enough to require urgent treatment. All patients taking medication at the time of entry were on a stable dose for at least 3 months and were willing and able to remain on a stable regime for the 3-month duration of treatment. Waiting-list subjects (n=46) showed no evidence of significant change on any of the dependent measures in the original trial and were not included in the present analysis ; nor were drop-outs (i.e. those who failed to attend on more than two occasions or who failed to provide adequate pretreatment and endpoint data ; n=19). Measures As in the original outcome study (Kenardy et al. 2003a), there were two principal dependent measures. The first was a single unweighted composite panic-anxiety measure to control for experimental error (Clark et al. 1994) in view of the large number of anxiety scales. This was calculated using the procedure recommended by Conners et al. (2001). The composite measure comprised data from each of 11 panic/anxiety measures: panic frequency ; patient and clinician-assessed panic severity/disability; StateTrait Anxiety Inventory (STAI; Spielberger et al. 1970); Fear Questionnaire subscales: Agoraphobia; Social; Blood/Injury (Marks & Mathews, 1979); Mobility Inventory for Agoraphobia: ‘Alone’ and ‘Accompanied’ (Chambless et al. 1985); the Body Sensations Questionnaire (BSQ) and the Agoraphobic Cognitions Questionnaire (ACQ) (Chambless et al. 1984). The other main dependent variable was a measure of clinically significant outcome adopted by Craske et al. (1991) and Clark et al. (1994), with high end-state functioning (ESF) defined as the absence of panic attacks over the preceding 2 weeks and an assessor panic-related distress/disability rating f2 (maximum 8), i.e. ‘slight ’.

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Assessments in the original study were undertaken at baseline, immediately after the 3-month active treatment period, and at the 6-month follow-up. The following outcome measures provided additional independent variables pre- and post-treatment: the Beck Depression Inventory (BDI; Beck et al. 1988); the Medical Outcomes Study 36-item Short Form Health Survey (SF-36; Ware & Sherbourne, 1992); and the Sheehan Disability Scale (SDS; Sheehan, 1986). Statistical analyses An examination of prognostic indices was conducted in relation to all three treatment groups combined. The pooling of subjects across treatments in the first instance was justified on the grounds that all three treatments involved CBT and followed the same content, the only differences being duration of treatment programme, frequency of therapist contact and form of delivery. In view of the large number of potential predictors, preliminary bivariate analyses were conducted to identify smaller subsets of potential predictors for inclusion in subsequent regression analyses. The relationship of each variable with each of the two main outcome measures was examined using bivariate Pearson correlations or a series of univariate logistic regression analyses, depending on whether the outcome measure was continuous or categorical. Predictors shown to be significant in relation to both dependent measures were included in subsequent multivariate regression analyses. Stepwise multiple regression analysis was conducted in which the post-test or followup score was the criterion and the prior test score on that same measure was forced to enter the equation before the predictor(s) of interest. The resulting change in R2 when the predictors are entered is thus readily interpreted as a measure of change or maintenance (Steketee & Chambless, 1992). The strengths of associations identified were estimated from the proportion of the variance in the dependent variable accounted for by the combination of independent (predictor) variables that entered each regression equation. In line with the recommendations of Steketee & Chambless (1992) that the results encompass both degree of change and determination of recovery, an analysis of predictors of high and low ESF was

also conducted by means of stepwise logistic regression. RESULTS Preliminary bivariate analyses revealed a number of significant results for both outcome measures, providing varying degrees of support for all of the above hypotheses. Despite the risk of Type I error, a normal a level of 0.05 was retained to help to identify those variables that might contribute some explanatory variance from subsequent regression analysis. Pretreatment associations with post-treatment outcome Hypothesis (a): Baseline symptom severity and outcome expectations Five variables relating to baseline severity of panic and anxiety were found to be significantly associated with both measures of clinical improvement. These were the Fear Questionnaire’s Agoraphobia (r=0.46, p<0.001) and BloodInjury (r=0.45, p<0.001) subscales; Mobility Inventory – Alone (r=0.49, p<0.001) and Accompanied (r=0.34, p<0.001) ; and the Trait measure of STAI (r=0.35, p<0.001). Age of first onset of panic also distinguished those with high and low ESF (exp b=1.06, p<0.05), with those experiencing panic attacks for the first time at a younger age having a poorer outcome. A similarly consistent trend on both dependent measures was also found for interviewer ratings of panic severity (r=0.21, p=0.05). Patients’ expectations of the likely effectiveness of treatment and their confidence in the treatment rationale were each significantly correlated with the post-treatment composite score (r=x0.23 and r=x0.25, p<0.05, respectively), although these relationships did not reach significance in distinguishing those with high and low posttreatment ESF. Hypothesis (b): Secondary associated disability/co-morbidity The presence of associated agoraphobia, depression, social anxiety and impairment of social, occupational and family relationship functioning from the SDS were included in the preliminary analyses. Two variables showed a significant correlation in the predicted direction

Prognostic indices with CBT for PD : predictors of outcome

with both dependent measures : an additional diagnosis of social anxiety (r=0.28, p<0.01) and the SDS rating of secondary impairment of family life (r=0.22, p<0.05). The only other significant results were bivariate correlations with the post-treatment composite measure only and included the other two aspects of impaired functioning from the SDS (i.e. work and social life : r=0.20, p<0.05 and r=0.30, p<0.01 respectively) and self- and interviewer ratings of depression (BDI : r=0.28, p<0.01 and HAMD: r=0.23, p<0.05). Having a co-morbid diagnosis of depression, generalized anxiety or obsessional-compulsive disorder was not shown to be associated with a poorer outcome. As predicted, associated agoraphobia was, but only in relation to the post-treatment composite score (r=0.24, p<0.05). Whether or not concomitant anxiolytics or antidepressant medication were being taken and the duration of their use, if relevant, were also unrelated to posttreatment outcome. Post-treatment associations with follow-up outcome Hypothesis (c): Agoraphobic cognitions With respect to the relationship between the persistence of dysfunctional agoraphobic cognitions at post-treatment and long-term outcome, there was a significant correlation with the follow-up composite score (r=0.56, p<0.001). This relationship was further supported by the results from the comparison between the high/low ESF groups (exp b=0.36, p<0.05). Hypothesis (d): Residual anxiety and agoraphobic avoidance As hypothesized, significant associations with both measures of long-term outcome, all in the predicted direction, were found for posttreatment patient and interviewer ratings of residual panic severity (r=0.50, p<0.001 and r=0.49, p<0.001, respectively), degree of agoraphobic avoidance, when unaccompanied (r=0.55, p<0.001), Fear Questionnaire – Agoraphobia subscale (r=0.57, p<0.001), SF-36 – Mental (r=x0.53, p<0.001) and Physical factors (r=x0.52, p<0.001), and degree of associated impairment of social (r=0.60, p<0.001), work (r=0.56, p<0.001) and family life (r=0.52, p<0.001).

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Hypothesis (e): Anxiolytic use Support was also found on both outcome measures for the hypothesis that those continuing to take anxiolytics at the end of CBT treatment would experience poorer outcome at follow-up compared to those who were not taking anxiolytic medication (r=0.36, p<0.01). Prediction of post-treatment outcome The above subset of variables, where a significant bivariate relationship with outcome was found, was entered into a series of stepwise multiple regression analyses, ensuring that the ratio of predictor variables to subjects was within appropriate limits (Green, 1991). Confirmatory analyses using stepwise logistic regression, using high/low ESF as the dependent variable, were also conducted. The results of pretreatment predictor analysis, summarized in Tables 1 and 2, show that only four variables emerged as collectively significant. These were patients’ expectations of outcome effectiveness ; Fear Questionnaire – Blood/Injury ; concomitant social anxiety; and degree of agoraphobic avoidance when alone. Collectively, these variables accounted for about 14% of the variance in the post-treatment composite score, although the last of these (agoraphobic avoidance) showed unacceptably high collinearity due to correlation with the precomposite measure that was entered first in the equation as a control for baseline differences on the dependent measure. However, subsequent logistic regression analysis, using high/low ESF as the binary outcome measure, provides additional evidence of the predictive value of this variable. In addition, age at first onset of panic disorder also emerged as significant, mirroring the results of the initial bivariate analyses, with all five variables correctly predicting 63% of the low-ESF group and 82% of the significantly recovered or high-ESF group. Post-treatment predictors of follow-up outcome Post-treatment predictors of outcome at followup were subject to the same analyses, the results of which are detailed in Tables 3 and 4. Two post-treatment measures were shown to be predictive of follow-up outcome from both multiple and logistic regression : the post-treatment use of anxiolytics and degree of impairment of

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Table 1.

Results of stepwise multiple regression analyses of pretreatment predictors of post-treatment composite panic/anxiety measures

Pretreatment predictor variable Step 1 Pretreatment Composite Score Step 2 Expectations re Outcome Step 3 Fear Questionnaire Blood/Injury Step 4 Co-morbid Social Anxiety Step 5 Mobility Inventory (‘Alone’)

Coefficients from final model (Step 5) Pretreatment Composite Score Expectations re Outcome Fear Questionnaire Blood/Injury Co-morbid Social Anxiety Mobility Inventory (‘ Alone ’)

R

Adjusted R2

DR2*

F(1, 97)

0.557 0.610 0.648 0.667 0.684

0.303 0.359 0.401 0.421 0.439

0.062 0.047 0.025 0.023

43.64*** 9.49** 7.68** 4.23* 4.06*

B

S.E.

b

Significance

Tolerance

0.238 0.032 0.018 0.260 0.135

0.141 0.010 0.007 0.120 0.067

0.217 0.240 0.242 0.172 0.224

0.093 0.002 0.015 0.032 0.047

0.349a 0.998 0.601 0.915 0.464a

S.E., a

Standard error. High collinearity : Pearson correlation coefficient of 0.73 between Pretreatment Composite and Mobility Inventory (‘ Alone ’) scores. * p<0.05, ** p<0.01, *** p<0.001.

Table 2. Final model (Step 5) of stepwise logistic regression analysis of pretreatment predictors of clinically significant post-treatment outcome (high end-state functioning) 95% CI for exp b Predictor Pre-Fear Questionnaire Blood/Injury (p=0.05) Social Anxiety** Expectation re Outcome* Age at first episode of panic disorder* Mobility Inventory (‘Alone’)*

b

S.E.

Wald

exp b

Lower

Upper

x0.057 1.652 x0.094 0.064 x0.444

0.029 0.566 0.043 0.029 0.224

3.718 8.531 4.812 4.712 3.945

0.945 5.216 0.910 1.066 0.641

0.892 1.722 0.837 1.006 0.414

1.001 15.804 0.990 1.129 0.994

S.E., Standard error; CI, confidence interval. * p<0.05, ** p<0.01.

Table 3.

Results of stepwise multiple regression analyses of post-treatment predictors of follow-up composite panic/anxiety measures

Post-treatment predictor variable Step 1 Post-treatment Composite Score Step 2 Sheehan Disability Scale (Social) Step 3 Use of Anxiolytics

R

Adjusted R2

DR2*

F(1, 83)

0.754 0.772 0.786

0.563 0.587 0.604

0.029 0.022

109.12*** 5.82* 4.58*

B Coefficients from final model (Step 3) Post-treatment Composite Score Sheehan Disability Scale (Social) Use of Anxiolytics Coefficients with Fear Questionnaire (Social) included Post-treatment Composite Score Sheehan Disability Scale (Social) Use of Anxiolytics Fear Questionnaire (Social) S.E.,

S.E.

b

Significance

Tolerance

0.647 0.058 0.284

0.097 0.025 0.132

0.589 0.203 0.153

0.000 0.021 0.035

0.610 0.632 0.922

0.737 0.074 0.264 x0.016

0.105 0.026 0.131 0.008

0.670 0.258 0.143 x0.179

0.000 0.005 0.046 0.052

0.496 0.572 0.916 0.551

Standard error. * p<0.05, *** p<0.001.

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Prognostic indices with CBT for PD : predictors of outcome

Table 4. Final model (Step 3) of stepwise logistic regression analysisa post-treatment predictors of clinically significant outcome at follow-up (high end-state functioning) 95% CI for exp b Predictor Post-ESF Post-treatment Use of Anxiolytics** Post-treatment Sheehan (Social)** Post-treatment Fear Questionnaire (Social) (p=0.05)

b

S.E.

Wald

exp b

Lower

Upper

1.006 x2.047 0.440 x0.093

0.643 0.644 0.142 0.048

2.453 10.109 9.643 3.725

2.736 0.129 1.553 0.911

0.776 0.037 1.176 0.829

9.640 0.456 2.050 1.001

S.E., a

Standard error ; CI, confidence interval. Post-treatment end-state functioning (ESF) status entered first as control for prior level on dependent measure. ** p<0.01.

social relationships. The Social subscale of the Fear Questionnaire just failed to reach significance (p=0.052). Nevertheless, in conjunction with the social impairment measure from the SDS, it may be considered to be consistent with the predictive importance of social support and ease of social functioning in determining the maintenance of treatment gains, being rather more influential in the prediction of high ESF at follow-up (82 % correct) compared to low ESF (52 % correct). The hypothesis that the persistence of dysfunctional agoraphobic cognitions at the end of active treatment would have a bearing on the maintenance of treatment gains was not supported from the analysis applied to all treatment groups combined. DISCUSSION Multivariate analysis of predictors of outcome at immediate post-treatment and at the 6-month follow-up, across all CBT treatment groups from the Kenardy et al. (2003 a) study, revealed only a small number of prognostic indices. Post-treatment outcome was predicted by baseline scores on the Fear Questionnaire – Blood/ Injury scale ; concomitant social anxiety ; degree of agoraphobic avoidance when unaccompanied ; patients’ general expectations of outcome ; and age at first onset of panic attacks. In each case greater baseline severity was predictive of poorer outcome. The blood/injury scale comprises a measure of the degree of phobic avoidance of injections/ minor surgery, hospitals, sight of blood and the thought of injury or illness. It is possible that such items may tap into more general, primary

health-related fears, commonly associated with panic disorder (Clark, 1986 ; Salkovskis, 1988 ; Hackmann, 2004). While such fears may be considered central to a cognitive model of panic, it may be that it is those automatic thoughts associated more directly with anxiety-mediated somatic arousal (palpitations, light-headedness, etc.) that are most accessible to change with CBT. If so, this may have some bearing on how we might ensure that more general underlying fears and vulnerability factors in the maintenance of panic are adequately addressed. The hypothesis that patients’ expectations of improvement would be predictive of outcome is also borne out by the results of this study, thus providing additional support for the findings of Clark et al. (1999). Patients with lower expectations that therapy will be effective in changing not only the frequency and severity of their panic attacks but also their irrational cognitions and phobic avoidance experience poorer outcome compared to those with higher levels of pretreatment optimism. The predictive significance of this variable from at least two independent studies highlights the need for it to be given due recognition in routine initial clinical assessment and treatment planning. Age of first experience of panic attacks was also found to contribute significantly to the prediction of clinically significant outcome and clearly did so independently of expectations regarding outcome, with which an inverse relationship might have been considered. However, age of onset of panic symptoms did correlate significantly with pretreatment ACQ and BSQ scores (in each case r=x0.20, p<0.05), suggesting that the earlier a panic attack is

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experienced, the stronger the dysfunctional beliefs and fears central to panic are in later years. As such, this finding is consistent with the reported importance of early intervention following initial experience of panic symptoms, even as limited symptom attacks, in preventing the subsequent development of panic disorder of clinical severity (Reed & Wittchen, 1998 ; Kenardy et al. 2003 b). Previous research has shown degree of agoraphobic avoidance to be significantly predictive of outcome and the present results provide further support for this relationship. This is apparent here, however, only for degree of avoidance ‘when unaccompanied ’. At a clinical level, a regular ability to confront formerly feared situations while unaccompanied is implicit in the concept of clinically significant change for the majority of those with associated agoraphobia. The prognostic significance of this variable, however, underscores the importance of its being adequately addressed in treatment. Regular exposure when alone, as opposed to accompanied, may be expected to have much greater benefits in terms of the emotional processing of anxiety and in targeting and modifying core dysfunctional beliefs relating to personal safety (Foa & Kozak, 1986). A degree of caution, however, is warranted in interpreting the results of stepwise multiple regression involving this variable because of fairly high collinearity. Thus, degree of agoraphobic avoidance, as measured by the Mobility Inventory, being a constituent of the composite measure, correlates highly, as expected, with the pretreatment composite score and clearly shares common variance in predicting outcome. Nevertheless, the results from logistic regression provide additional support for the predictive significance of agoraphobic avoidance in relation to an independent measure of clinically significant improvement. Finally, co-morbidity, as hypothesized, was also found to be predictive of post-treatment outcome. Contrary to expectation, the coexistence of agoraphobia, as distinct from PD alone, was not found to be a significant predictor in this study, but the presence of additional social anxiety was. Thus, the presence of co-morbid social anxiety, based on fears of anxiety symptoms being perceptible to others and of resultant negative evaluation, is associated with less

improvement in this trial. It is acknowledged, however, that both situational and interoceptive exposure for PD aim to reduce anxiety in relation to somatic arousal, in which cognitive reappraisal is primarily concerned with the perceived physical consequences of anxiety. Where the perceived consequences are largely social, however, additional targeted cognitive restructuring is also indicated, but may have been given insufficient weight in the present study. Contrary to our hypothesis based on a central element of the cognitive model of panic (Clark, 1986), and contrary also to the results of Clark et al. (1994, 1999), no significant association was found between the persistence of dysfunctional thoughts relating to physical sensations at the end of active treatment and subsequent relapse at the 6-month follow-up, as measured by the BSQ and ACQ. Clark et al. (1994, 1999) observed this relationship only for the Body Sensations Interpretations Questionnaire – Panic (Clark et al. 1997), a schema-based measure designed to assess a general disposition to misinterpret bodily sensations even in the absence of such sensations and symptoms. The ACQ, however, was designed as a measure of automatic thoughts occurring at the time of an anxiety episode. Complete data on the former measure of core underlying beliefs, representing a vulnerability to PD according to cognitive theory, were not available in this study. In addition, not all treatments in the present study allowed equal time to address such cognitive factors in preparation for followup and the examination of the differential effects of treatments in modifying such central dysfunctional cognitions, addressed in the subsequent paper, may prove more useful than an analysis involving all treatment groups combined. Clear support, however, was found for the hypothesis that patients continuing to take anxiolytic drugs post-treatment would be less likely to maintain treatment gains compared to those who were psychotropic drug free. Such results from both multiple and logistic regression essentially replicate the findings of Otto et al. (1996) and cannot be explained by differences in baseline severity, as the analyses controlled for such a potential effect. The most commonly prescribed anxiolytics in the present

Prognostic indices with CBT for PD : predictors of outcome

study were benzodiazepines and, as Otto et al. (1996) also acknowledged, this negative relationship with the maintenance of remission may be specific to this class of anxiolytics. Marks et al. (1993) also found that even shortterm use of benzodiazepines seemed to impair the maintenance of improvement following exposure treatment. As in the latter study, those in the present sample taking medication were required to remain on a stable drug regime throughout the active treatment period only and so it is possible that the present results may be attributed, at least in part, to the effects of state-dependent learning and ‘rebound ’ anxiety. Moreover, the presence of safety cues during situational and interoceptive exposure and drug-related attributions of improvement may have impaired adaptive cognitive reappraisal (Basoglu et al. 1994 ; Wells et al. 1995; Otto & Gould, 1996). It is also possible that anxiolytic treatment may interfere with the activation of fear structures during exposure, a hypothesized prerequisite for effective emotional processing (Foa et al. 2002). Finally, and consistent with one of the pretreatment predictors of post-treatment outcome, degree of continuing social disability, as a result of residual anxiety symptoms, is a significant determinant of follow-up outcome. This is also supported by the near significant coefficient for the Fear Questionnaire (Social) subscale (p=0.05). Such evidence suggests the need to ensure that treatment encompasses the social sequelae of PD and agoraphobia in preventing relapse and parallels related findings on the role of interpersonal factors in the maintenance and remission of generalized anxiety (Durham et al. 1997 ; Newman, 2000). In conclusion, the results of the present study provide a useful endorsement of the predictive significance of a number of key pre- and posttreatment variables in relation to CBT outcome for PD. These findings apply only to outcome to CBT in general, and do not inform choice of CBT format despite increasing interest in brief and other ‘ non-standard ’ forms of its delivery. The second part of this study aims to address this issue. DECLARATION OF INTEREST None.

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