East Asian Arch Psychiatry 2017;27:150-5

ORIGINAL ARTICLE

Dr Sei Ogawa, MD, PhD, Department of Psychiatry and Cognitive-Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Dr Masaki Kondo, MD, PhD, Department of Psychiatry and Cognitive- Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Dr Keiko Ino, MD, Department of Psychiatry and Cognitive-Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Dr Toshitaka Ii, MD, Department of Psychiatry and Cognitive-Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Dr Risa Imai, MD, Department of Psychiatry and Cognitive-Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Dr Tatsuo Akechi, MD, PhD, Department of Psychiatry and Cognitive- Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Dr Toshi A. Furukawa, MD, PhD, Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, Japan.

Address for correspondence: Dr Sei Ogawa, Department of Psychiatry and Cognitive-Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 Japan. Tel: (81) 528538271; Fax: (81) 528520837; 

Email: seiogawa1964@nifty.com

Submitted: 20 February 2017; Accepted: 14 August 2017

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Introduction

Panic disorder (PD) is a common mental disorder with a lifetime prevalence of approximately 3%.¹ It is associated with significant disability and diminished quality of life.² Patients with PD commonly have a broad psychopathology. In all, 50% to 80% of PD patients meet the criteria for at least one other diagnosis, most typically other anxiety or mood disorders.^3,4 Panic disorder with co-morbid psychiatric disorders is thought to be a severe condition. For example, the co-morbidity of PD with depressive disorder is thought to be associated with greater symptom severity⁵ and poorer treatment response.⁶ Successful treatment of PD is related to improvement in co-morbid psychiatric symptoms.

In particular, PD with agoraphobia (PDA) is common and being one of the most handicapping anxiety disorders. Approximately two-thirds of PD patients alsohave agoraphobia.⁸ Patients with PDA have many clinical problems. Their remission rates are lower and their relapse rates are higher than those with PD alone.⁹ Moreover, PDA is associated with greater functional impairment and greater disability.¹⁰

Panic disorder with agoraphobia can be conceptualised as fear of fear (FOF), or a tendency to respond fearfully to benign bodily sensations, and figures remarkably in several theoretical accounts of PDA.^11,12 Fear of fear comprises 2 elements: maladaptive thoughts about the consequences of becoming anxious and a fear of bodily sensations associated with a panic attack.¹³ In a number of studies, FOF was associated with agoraphobic severity.¹³ Moreover, FOF is related to avoidance behaviour after treatment.¹⁴

The efficacy of cognitive behavioural therapy (CBT) for PDA is well established.¹⁵ There is now evidence that CBT for a targeted anxiety disorder causes positive outcomes in a broad range of psychopathologies.^3,16 Although many researchers have performed mediation analyses to investigate the specific mechanism of changes during CBT, there is limited evidence about how CBT works for PDA.¹⁷ Improvement of FOF may mediate the acute-phase treatment effect on PDA symptoms in CBT.¹⁸ As mentioned above, successful CBT for PDA is associated with changes in co-morbid psychiatric symptoms, although it is unclear whether changes in FOF are also related to changes in broader psychiatric symptoms during CBT for PDA.

The present study aimed to examine the relationship of changes in FOF and changes in broader psychopathology over the course of CBT for PDA.

Methods

Participants

A total of 205 Japanese patients with PDA who attended the group CBT programme participated in the present study between October 2001 and February 2015. All of the patients met the following inclusion criteria: (i) principal Axis I diagnosis of PDA according to the DSM-IV criteria, as assessed by the Structured Clinical Interview for DSM-IV (SCID)¹⁹; (ii) free from benzodiazepine use prior to CBT entry, since these drugs may interact negatively with exposure treatments.²⁰ Use of benzodiazepine to control anxiety was not permitted during the course of CBT; and (iii) highly motivated to undergo CBT. Exclusion criteria were current psychosis, bipolar disorder, and substance use disorder. Use of antidepressants to control anxiety or depression was permitted throughout the CBT period because these drugs do not interfere with CBT treatments.²¹ The patients provided written informed consent after receiving a full explanation of the purpose and procedures of the study.

The study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Nagoya City University Graduate School of Medical Sciences, Japan.

Treatments

We followed the established CBT treatment manual for PDA.9 Treatments were conducted in groups of 3 to 4 patients led by a principal therapist and a co- therapist. The 2 therapists were psychiatrists or clinical psychologists with at least 2 years of clinical experience. A total of 8 male and 6 female therapists conducted the CBT. The treatment consisted of 10 sessions, each lasting approximately 2 hours. The first through ninth sessions were held weekly, and the tenth session was conducted 4 weeks after the ninth session. The first 2 sessions included psycho-education about the nature of anxiety, panic and agoraphobia and provided a rationale for training in breathing retraining. From the third session on, cognitive restructuring, situational and interoceptive exposure were introduced, and patients were asked to try to formulate rational thoughts and to perform self-exposure tasks without therapists to reproduce both situational and interoceptive phobic cues during and between sessions.

Assessment

All patients completed the SCID at baseline, including the anxiety and mood disorder sections. This interview was conducted by one of the therapists in charge of the programme. All researchers were trained in carrying out the SCID and completing the Panic Disorder Severity Scale (PDSS). All subjects were assessed with the following instruments pre- and post-treatment.

Symptom Checklist–90 Revised

The Symptom Checklist–90 Revised (SCL-90-R) is widely used to assess general psychopathology.²² It contains 90 items, subdivided into 9 subscales of somatisation, obsessive-compulsive disorder, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. Each item was scored between 0 (not at all) and 4 (extremely), and the average of the relevant items was taken as the subscale score. The reliability and validity of the Japanese version have been reported.^23,24

Agoraphobic Cognitions Questionnaire

The Agoraphobic Cognitions Questionnaire (ACQ) is a 14-item self-report instrument to assess maladaptive thoughts concerning catastrophic consequences of experiencing anxiety in FOF. Frequency of each item is rated on a 5-point scale ranging from 1 (thought never occurs) to 5 (thought always occurs). Good reliability and validity have been shown for both original and Japanese versions of this questionnaire.^13,25

Body Sensations Questionnaire

The Body Sensations Questionnaire (BSQ) is a 17-item self-report instrument to assess the fear evoked by panic- related bodily sensations in FOF. Degree of each item is rated on a 5-point scale ranging from 1 (not frightened or worried by this sensation) to 5 (extremely frightened by this sensation). Reliability and validity of original and Japanese versions of this questionnaire have been established.^13,26

Panic Disorder Severity Scale

The PDSS is an interview-based, 7-item scale to assess overall severity of PD in which the clinician rates the severity of 7 features of PD on a scale ranging from 0 (none) to 4 (extreme). The 7 areas include the frequency of panic attacks; distress during the panic attacks; anticipatory anxiety; agoraphobic fear / avoidance; interoceptive fear / avoidance; work impairment / distress; and impairment of social functioning. The reliability and validity have been reported for both original and Japanese versions.^27,28

Statistical Analyses

All data were examined using the SPSS (Windows version 18.0; SPSS Inc., Chicago [IL], US). The pre- and post- treatment data were used to calculate change scores (Δ) for each variable. First, we used an independent-samples t test and χ2 tests to compare the demographic and clinical data among the patients who completed the programme and those who did not. Second, we used paired t tests to compare the pre- and post-therapy scores. Third, simple correlations among change scores of independent variables were examined. Generally, if the correlation between 2 variables (including those in multiple linear regression analysis) is high, it may cause multicollinearity that influences interpretation of the findings. If 2 independent variables had a correlation of > 0.7, we could omit one in multiple regression analysis. Last, to examine the predictors of changes in co-morbid psychiatric symptoms, we performed multiple linear regression analysis. We used the changes in 9 subscales of SCL-90-R as dependent variables, and the changes in the total scores of ACQ and BSQ as independent variables controlling the changes in the PDSS total score. All statistical tests were 2-tailed. Except for multiple linear regression analysis, an alpha value of < 0.05 was considered statistically significant. In order to counteract the problem of multiple comparisons, we used the Bonferroni correction. In multiple linear regression analysis, an alpha value of < 0.005 was considered statistically significant.

Results

Of 205 patients, 28 (13.0%) who started CBT treatment dropped out prematurely from the programme: 16 were lost to follow-up, 4 discontinued because of clinical relapse, 4 because of personal choice, and 4 for other reasons. Table 1 shows their baseline demographic and clinical characteristics. No statistically significant differences were found between the subgroups. Of 102 patients who completed the trial and had used an antidepressant at baseline, 21 tapered or stopped usage at the endpoint.

Table 2 shows that all SCL-90-R subscale scores at baseline were higher than those of Japanese community sample,24 and all post-treatment scores were significantly lower than the pre-treatment scores (p < 0.001).

Table 3 shows that all bivariate correlations of change scores of PDSS, ACQ, and BSQ were < 0.6 implying that the correlation was relatively low and might not cause multicollinearity.

In regression analysis (Table 4), the reduction in ACQ score was related to the decrease in all SCL-90-R subscale scores. Reduction in BSQ score was significantly associated with decrease in anxiety only (p < 0.01). Reduction in PDSS score was not related to any SCL-90-R subscale changes.

Discussion

This study investigated the relationship of FOF and broad areas of psychopathology in PDA patients over the course of CBT in Japan using multiple regression analysis. The results show that changes in maladaptive thoughts concerning catastrophic consequences of experiencing anxiety predicted broad dimensions of psychopathological changes, whereas changes in the fear evoked by panic- related bodily sensations predicted anxiety only, in patients

Table 1. Baseline characteristics of the patients.*

Abbreviations: ACQ = Agoraphobic Cognitions Questionnaire; BSQ = Body Sensations Questionnaire; PDSS = Panic Disorder
Severity Scale.

* Data are shown as No. (%) of subjects or mean ± standard deviation.

Table 2. Pretreatment and post-treatment rating scale scores (n = 177).*

Abbreviations: ACQ = Agoraphobic Cognitions Questionnaire; BSQ = Body Sensations Questionnaire; PDSS = Panic Disorder
Severity Scale; SCL-90-R = Symptom Checklist–90 Revised.

* Data are shown as mean ± standard deviation.

Table 3. Correlations among changes in PDSS, ACQ, and BSQ (n = 177).

Abbreviations: ACQ = Agoraphobic Cognitions Questionnaire; BSQ = Body Sensations Questionnaire; N/A = not applicable; PDSS = Panic Disorder Severity Scale.

* p < 0.01.

with PDA during CBT. On the contrary, reduction in PD severity was not related to changes in co-morbid psychiatric symptoms over the course of CBT for PDA.

These results are consistent with the findings that cognitive factors are an important transdiagnostic target of treatment.²⁹ Improvement in FOF, especially disorder- specific maladaptive cognitions, may mediate treatment effects on co-morbid psychiatric symptoms beyond those of PDA during CBT.

Furthermore, our results suggest that the changes in PD severity may not contribute to improvement in broad areas of psychopathology. Changes in maladaptive cognitions may be superior to changes in PDA symptoms in predicting improvements in co-morbid psychiatric symptoms during CBT. This work emphasises the importance of considering cognitive factors in CBT for PDA.

As mentioned above, PD patients commonly have broad psychiatric symptoms. From the clinical point of view, it may be useful to focus on achieving cognitive changes in preference to PDA symptom changes during CBT for the purpose of improving broader psychopathology.

The present study had several limitations. First, the study did not involve a control group. It is not certain whether the significant reduction in the symptomatology or maladaptive cognitions were due to CBT treatment rather than the passage of time. A randomised controlled trial with an appropriate control group is needed to investigate the efficacy of CBT for PDA. Second, because independent and dependent variables were measured at the same time point, we were not able to assess whether changes in maladaptive cognitions preceded changes in broader areas of psychopathology. It is necessary to use a design with temporal delay between assessments of maladaptive thoughts and broader psychiatric symptoms in future studies. Third, our multiple regression analysis used only 2 elements of FOF as independent variables, therefore our results accounted for less than half of the variance in changes in broader areas of psychopathology. Lastly, we used a standardised CBT manual, and did not record the interviews or performances to ensure the accuracy of materials provided to patients in the course of CBT.

Conclusions

We examined the relationship of FOF and broad areas of psychopathology in PDA patients during CBT using multiple regression analysis in Japan. Changes in maladaptive cognitions concerning potential harm of a panic attack may predict changes in broad areas of psychopathology in PDA patients over the course of CBT. For the purpose of improving a broad range of psychiatric symptoms in patients with PDA, more attention to maladaptive cognition changes during CBT is warranted.

Table 4. Unique predictors of changes in co-morbid psychiatric symptoms (n = 177).*

Abbreviations: ACQ = Agoraphobic Cognitions Questionnaire; ANX = anxiety; BSQ = Body Sensations Questionnaire; DEP = depression; HOS = hostility; I-S = interpersonal sensitivity; O-C = obsessive-compulsive disorder; PAR = paranoid ideation; PDSS = Panic Disorder Severity Scale; PHOB = phobic anxiety; PSY = psychoticism; SCL-90-R = Symptom Checklist–90 Revised; SOM = somatisation.

* Data are shown as standardised beta coefficients.

† p < 0.01.

‡ p < 0.001.

Acknowledgements

This study was supported by the Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology from Japan (23530910).

Declaration

All authors have disclosed no conflicts of interest.

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