Panic disorder (PD) affects up to 5% of the population at some point in life and is often associated with substantial functional morbidity [Reference Dow, Kenardy, Johnston, Newman, Taylor and Thomson14,Reference Dow, Kenardy, Johnston, Newman, Taylor and Thomson15,Reference Roy-Byrne, Craske and Stein43]. Studies in both community (Epidemiologic Catchment Area study [Reference Markowitz, Weissman, Ouellette, Lish and Klerman32]; National Comorbidity Survey [Reference Eaton, Kessler, Wittchen and Magee16]) and clinical samples have consistently shown that PD markedly compromises quality of life (QoL) and psychosocial functioning [Reference Candilis, McLean, Otto, Manfro, Worthington and Penava11,Reference Carrera, Herran, Ayuso-Mateos, Sierra-Biddle, Ramirez and Ayestaran12,Reference Ettigi, Meyerhoff, Chirban, Jacobs and Wilson17,Reference Fyer, Katon, Hollifield, Rassnick, Mannuzza and Chapman23,Reference Hollifield, Katon, Skipper, Chapman, Ballenger and Mannuzza26,Reference Katon, Hollifield, Chapman, Mannuzza, Ballenger and Fyer28,Reference Mendlowicz and Stein35,Reference Olatunji, Cisler and Tolin39,Reference Schonfeld, Verboncoeur, Fifer, Lipschutz, Lubeck and Buesching45]. For example, Candilis et al.[Reference Candilis, McLean, Otto, Manfro, Worthington and Penava11] showed that all mental and physical health scale scores of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) were lower in patients with PD than in the normal population. Fava et al.[Reference Fava, Rafanelli, Ottolini, Ruini, Cazzaro and Grandi19, Reference Fava, Rafanelli, Tossani and Grandi20] reported that even remitted patients with PD and agoraphobia had significantly less psychological well-being compared to healthy controls. Thus, it has been suggested that measurement of treatment outcome in PD should not be limited to monitoring symptom changes but should also include different domains of QoL.
Some outcome studies showed significant improvements in QoL in patients with PD following treatment with antidepressants or benzodiazepines [Reference Bandelow, Stein, Dolberg, Andersen and Baldwin8,Reference Hoehn-Saric, McLeod and Hipsley25,Reference Jacobs, Davidson, Gupta and Meyerhoff27,Reference Lecrubier and Judge31,Reference Mavissakalian, Perel, Talbott-Green and Sloan33,Reference Michelson, Lydiard, Pollack, Tamura, Hoog and Tepner36,Reference Pohl, Wolkow and Clary40–Reference Rapaport, Pollack, Wolkow, Mardekian and Clary42]. However, although cognitive-behavioral therapy (CBT), given individually or in a group setting, is the best empirically supported psychotherapeutic treatment for PD [Reference Furukawa, Watanabe and Churchill22,Reference Roy-Byrne, Craske and Stein43,Reference Ruhmland and Margraf44], little is known about the impact of CBT on QoL. Very few studies explored QoL following CBT, and reported that the effects of CBT may extend beyond PD symptom reduction to QoL [Reference Heldt, Blaya, Isolan, Kipper, Teruchkin and Otto24,Reference Kenardy, Dow, Johnston, Newman, Thomson and Taylor29,Reference Telch, Schmidt, Jaimez, Jacquin and Harrington49].
Thus, further research is clearly needed to establish whether PD symptom improvement following CBT is related to improved QoL. The present study, therefore, aimed at providing insight into several questions. Firstly, we compared QoL in patients with PD with normative data obtained from a large German population sample. Secondly, we examined the relationship between specific symptoms of PD and QoL, controlling for the potential confounding effect of depression. Thirdly, changes of different domains of QoL following cognitive-behavioral group therapy (CBGT) were investigated. We hypothesized that significant improvement in the majority of QoL domains would be observed. And finally, the relationship between changes in PD symptoms and QoL following CBGT was investigated. Our hypothesis was that a stronger decrease in PD symptoms would be associated with a stronger improvement in QoL.
2 Materials and methods
A total number of 55 outpatients were consecutively recruited at the Behaviour Therapy Unit at the Department of Psychiatry and Psychotherapy (University Hospital of Hamburg, Germany). Thirty-two patients (58%) were diagnosed with PD without agoraphobia, 23 (42%) with PD with agoraphobia, according to DSM-IV. Twenty-two patients (40%) had one or two comorbid axis I disorders. The most frequent comorbid diagnosis was major depression (N = 15; 28%), others were obsessive-compulsive disorder (N = 4); dysthymia (N = 3); social phobia (N = 2); anorexia nervosa (N = 1); alcohol abuse (N = 1); generalized anxiety disorder (N = 1).
Thirty-four patients (62%) were women, patients’ mean age was 40 years (± 11.3). Fifty patients (91%) participated in the post-treatment and 43 patients (78%) in the follow-up examination. Comparisons of completers with non-completers showed no significant differences in gender, age, and pre-treatment scores for the SF-36, Panic and Agoraphobia Scale (PAS), and Beck Depression Inventory (BDI) (data not shown, all P > 0.1).
QoL was measured with the German version [Reference Bullinger and Kirchberger10] of the SF-36 [Reference Ware and Sherbourne52], a generic and descriptive instrument for assessment of QoL [Reference Mortimer and Segal38]. Taken from the survey used in the Medical Outcomes Study, the SF-36 is a 36-item questionnaire, designed to evaluate various aspects of health from the individual's point of view. Factor analysis has validated the existence of the following eight scales which fall into either a physical or mental health component:
• limitations in physical activities because of health problems;
• limitations in usual role activities because of physical health problems;
• bodily pain;
• general health perceptions;
• vitality (energy and fatigue);
• limitations in social activities because of physical or emotional problems;
• limitations in usual role activities because of emotional problems;
• general mental health (psychological distress and well-being).
The physical health component of the SF-36 includes the first four scales, whereas the mental health component includes the other four scales. The SF-36 has been used in a wide range of disease-related studies. It is the most widely used instrument for measuring QoL in anxiety disorders [Reference Mendlowicz and Stein35]. The SF-36 can be used in repeated measures over time [Reference Mendlowicz and Stein35, Reference Moritz, Rufer, Fricke, Karow, Morfeld and Jelinek37]. It is scored from 0 to 100 with higher scores indicating better QoL. Validity and reliability of the SF-36 are satisfactory to excellent for both the original American and the German versions [Reference Bullinger and Kirchberger10, Reference McHorney, Ware and Raczek34]. Cronbach's Alpha Coefficients of all domain scales and the physical and mental summary scales of the American version of the SF-36 are between 0.7 and 0.9 [Reference Tsai, Bayliss and Ware50,Reference Ware and Gandek51,Reference Ware, Snow, Kosinski and Gandek53]. Similarly, most studies of the German version of the SF-36 showed that Cronbach's Alpha Coefficients were higher than 0.7 for all domain scales and the physical and mental summary scales [Reference Bullinger and Kirchberger10].
The clinician-rated version of the PAS [Reference Bandelow4] contains 13 items with Likert-type scales (from 0 to 4). The following five subscales were derived by factor analysis and logistic regression:
• panic attacks, including the items frequency, severity and duration;
• agoraphobia, including frequency, number and relevance of situations;
• anticipatory anxiety, including frequency and severity;
• disability, including family, social relationships and employment;
• worries about health, including worries about health damage by panic attacks and assumption of organic disease.
The scale was validated on a cross-section of 452 patients with PD [Reference Bandelow, Broocks, Pekrun, George, Meyer and Pralle6]. In addition, previous studies have demonstrated that the PAS is appropriate for use in a variety of clinical and research environments and, given its sensitivity to changes over time, a useful tool for assessing treatment efficacy in PD trials [Reference Bandelow4,Reference Bandelow, Broocks, Pekrun, George, Meyer and Pralle6,Reference Bandelow, Brunner, Broocks, Beinroth, Hajak and Pralle7]. Depressive symptoms were assessed with the BDI [Reference Beck, Ward, Mendelson, Mock and Erbaugh9].
CBGT consisted of psychoeducation, self-monitoring, therapist-guided exposure and self-exposure (with an emphasis of anxiety management, in order to improve patients’ ability to cope with distressing emotions), cognitive restructuring (including the evaluation of patients’ exposure experiences and their individual beliefs and appraisals), and progressive muscle relaxation. The program finished with the discussion of relapse prevention strategies.
Overall, nine groups were conducted; five to seven patients participated in each group that was led by two cognitive-behavioral therapists. Therapists were either licensed cognitive-behavior therapists, skilled and experienced in treating patients with anxiety disorders, or had reached an advanced level in their CBT training. They all received supervision by a senior cognitive behavioral therapist on a weekly basis. The fully manualized CBGT protocol [Reference Alsleben, Weiss and Rufer2] consisted of five weekly sessions of 150 minutes each (including a 15 minutes break), which, in terms of total treatment time, corresponds to fifteen 50 minutes sessions over a period of five weeks. Extended treatment sessions of 150 minutes were required particularly for exposure in vivo, which was a key element of CBGT. For a more detailed description of the CBGT protocol, see the treatment manual [Reference Alsleben, Weiss and Rufer2].
Nineteen patients (35%) received psychopharmacological medication before entering the study, mostly selective serotonin reuptake inhibitors. Nearly all patients kept their medication unchanged throughout group therapy and follow-up. Only five patients changed or stopped medication throughout group therapy, none of them started new medication. Six patients changed their medication during the follow-up period. None of the patients received additional psychotherapy during the group therapy period. At follow-up, 11 patients were currently receiving individual psychotherapy.
The study was approved by the ethics committee of the Ärztekammer Hamburg, Germany. Written informed consent was obtained from all patients before their inclusion in the study. None of the patients refused to participate in the study. Entry criteria for this study consisted of the following: patients had to be diagnosed by an experienced clinician with the primary diagnosis of PD with or without agoraphobia and to have a score of 7 or more on the clinician-rated version of the PAS, an empirically derived cut-off indicating at least mild symptom severity [Reference Bandelow5]. The Mini-International Neuropsychiatric Interview [Reference Sheehan, Lecrubier, Sheehan, Amorim, Janavs and Weiller48] for DSM-IV (German version [Reference Ackenheil, Stotz, Dietz-Bauer and Vossen1]), a reliable and valid structured diagnostic interview, was used to confirm the diagnosis of PD with or without agoraphobia and to establish comorbid diagnoses. Exclusion criteria were: current or past psychotic disorders, organic mental disorders, current substance dependency and an acute risk of suicide. At baseline, week six (post-treatment), and week 30 (six-month follow-up), clinician-rated and self-rated scales were assessed. Clinically experienced and specifically trained interviewers, who were not involved in the treatment process, conducted all clinician ratings. A given patient was always assessed by the same interviewer.
2.5 Statistical analyses
One-sample t-tests were used to compare the SF-36 mean scores of PD patient in our sample with standard values in healthy subject as reported in the norm study [Reference Bullinger and Kirchberger10]. For evaluating the relationship between baseline anxiety and baseline QoL scores, Pearson correlations were calculated. Three-step multiple linear regression models were performed to evaluate the associations between specific PD symptoms and QoL after controlling for depression and the presence of comorbid disorders. The SF-36 mental and physical health scores respectively served as dependent variables. BDI score were firstly entered as independent variables into the equation. In a second step, the presence of comorbid disorders (without comorbid disorder = 0; presence of comorbid disorder = 1) and finally, the PAS subscale scores were entered into the model.
The scores of SF-36, PAS, and BDI were submitted to univariate analyses of variance (ANOVA) with repeated measures to investigate the change of clinical symptoms and QoL between baseline, post-treatment, and follow-up. When the sphericity assumption was violated, P-values were Greenhouse-Geisser corrected. Effect sizes were estimated using partial eta2. Partial eta2 is calculated for each factor in ANOVA and describes the proportion of total variability attributable to that factor. According to Cohen [Reference Cohen13], eta2 values of 0.0099, 0.0588 and 0.1379 correspond to small, medium and large effect sizes, respectively. For all analyses of symptom and QoL changes, both completers and intention to treat analyses (by carrying the last observation forward [Reference Arntz3, Reference Shao and Zhong46]) were calculated.
To determine the possible association between improvement in anxiety symptoms and improvement in QoL, two-factorial ANOVA (group [responder, non-responder] × time [baseline, follow-up]) on SF-36 subscales were calculated. Repeated measures analysis of covariance (ANCOVA) was conducted to control for potentially confounding effects of baseline BDI scores, and three-factorial repeated measures ANOVA to control for the presence of comorbid disorders. In all analyses, the level of significance was set at P ≤ 0.05 (two-sided). The Statistical Package for Social Sciences, version 15.0 (SPSS, Chicago, Ill, USA), was used for all calculations.
3.1 QoL in patients with PD compared to healthy subjects
Fig. 1 presents the mean scores of SF-36 subscales in the present sample at baseline (N = 55) and in healthy participants of the German SF-36 norm population (at least N = 906 subjects per subscale) [Reference Bullinger and Kirchberger10]. Patients’ mean scores in all SF-36 subscales were substantially lower than those of the healthy subjects. In all subscales, except for the physical functioning subscale (z-score: −1.78), PD patients’ z-scores were approximately 2 to 4 standard deviations lower than those of the healthy sample.
3.2 Association between QoL and PD symptoms at baseline
At baseline, both SF-36 mental health scores (R = −0.47; P < 0.001) and physical health scores (R = −0.30; P < 0.05) were negatively correlated with PAS total scores. Linear regression analyses, controlled for BDI scores and the presence of comorbid disorders, showed significant associations between lower SF-36 mental health scores and both higher PAS agoraphobia scores (β = −2.70; t = −2.41; P < 0.05) and PAS disability scores (β = −3.95; t = 3.65; P < 0.01). Furthermore, SF-36 physical health was associated with PAS worries about health (β = −2.73; t = −2.16; P < 0.05).
3.3 Changes in QoL domains and PD features following CBGT
Table 1 displays the SF-36 and PAS mean scores at baseline, post-treatment and follow-up for study completers (N = 43). ANOVA with repeated measures revealed that all except two out of eight SF-36 subscales and all five subscales of the PAS improved significantly over time, with large effect sizes. The physical functioning subscale of the SF-36 showed a statistical trend (P = 0.06) toward improvement, whereas the vitality subscale did not change significantly over time. Intention to treat analyses (by carrying the last observation forward) did not substantially change these results.
3.4 Association between improvement in PD symptoms and QoL
A ≥ 50% reduction on the global PAS scale occurred in 27 (63%) patients from baseline to follow-up. These patients were categorized as responders, in accordance with previous studies [Reference Heldt, Blaya, Isolan, Kipper, Teruchkin and Otto24]. At baseline, most SF-36 subscale scores were comparable between responders and non-responders, except for three physical subscales: physical functioning (t = −2.47; df = 41; P < 0.05), role-physical (t = (3.83; df = 41; P < 0.001), and general health (t = −3.71; df = 41; P = 0.01). At follow-up, responders showed substantially higher scores on all subscales compared to non-responders:
• physical functioning (t = 5.59; df = 41; P < 0.001);
• role-physical (t = 5.04; df = 41; P < 0.001);
• pain (t = 4.31; df = 41; P < 0.001);
• general health (t = 5.05; df = 41; P < 0.001);
• vitality (t = 3.59; df = 41; P = 0.01);
• social functioning (t = 2.41; df = 41; P < 0.05);
• role-emotional (t = 5.08; df = 41; P < 0.001);
• mental health (t = 3.12; df = 41; P < 0.01).
Two-factorial ANOVA (group [responder, non-responder] × time [baseline, follow-up]) with repeated measures on SF-36 subscales showed significant main effects of time for role-physical, general health, social functioning, role-emotional and mental health (all P < 0.05). Significant group by time interactions were found for physical functioning (F = 11.86; df = 40; P < 0.01), pain (F = 11.86; df = 40; P < 0.01), vitality (F = 11.40; df = 40; P < 0.01), role-emotional (F = 12.51; df = 40; P < 0.01) and mental health (F = 13.00; df = 40; P < 0.01). These associations remained significant after controlling for depression and the presence of comorbid disorders.
The present study examined physical and mental dimensions of QoL and different aspects of PD following a brief CBGT program for PD. At baseline, we observed substantially decreased QoL in all domains, which is in line with the literature [Reference Candilis, McLean, Otto, Manfro, Worthington and Penava11,Reference Hollifield, Katon, Skipper, Chapman, Ballenger and Mannuzza26,Reference Katon, Hollifield, Chapman, Mannuzza, Ballenger and Fyer28,Reference Schonfeld, Verboncoeur, Fifer, Lipschutz, Lubeck and Buesching45]. Furthermore, also in accordance with previous studies [Reference Heldt, Blaya, Isolan, Kipper, Teruchkin and Otto24, Reference Telch, Schmidt, Jaimez, Jacquin and Harrington49], we found that frequency, severity and duration of panic attacks were not related to QoL. In contrast, agoraphobia (including frequency of avoidance behavior, number of avoided situations, and importance of avoided situations), disability (in family and social relations, pleasure activities and employment or housework), and worries about health were significantly associated with decreased QoL. This clinically relevant finding suggest that these aspects of PD, which affect patients’ live seriously and persistently, are particularly bothersome to patients and therefore deserve foremost clinical attention.
Our results further imply that emotional and physical aspects of QoL improved following CBGT, even after controlling for depression. This improvement was associated with a decrease of PD symptoms. These encouraging results support the view that the effects of brief CBGT for PD are not limited to reduction in PD symptoms [Reference Heldt, Blaya, Isolan, Kipper, Teruchkin and Otto24]. However, the vitality subscale did not improve significantly over time. This subscale is bipolar in nature; scores above the midpoint of 50 represent well-being whereas scores below 50 represent limitations or disability. The maximum score of 100 does not denote a mere absence of problems but positive health states (e.g., energy, pep and well-being). Thus, considering that no significant improvements in vitality occurred following CBGT, additional interventions designed to target this aspect of QoL may be necessary. For example, in generalized anxiety disorder, the addition of a specific psychotherapeutic strategy for enhancing well-being [Reference Fava18] showed significant advantages compared to CBT alone [Reference Fava, Ruini, Rafanelli, Finos, Salmaso and Mangelli21].
However, when interpreting our findings, it is important to consider that the study was conducted as an open trial. We compared baseline data with normative data obtained from a large German population sample [Reference Bullinger and Kirchberger10], but we did not have a control group. Therefore, it is not possible to draw causal conclusions about the decrease of QoL and CBGT. Furthermore, the six months follow-up was naturalistic, without control of the nature of additional treatment that some patients obtained. It is possible that, for example, the individual psychotherapy, which 11 of 55 patients started during the follow-up period, has contributed to the maintenance of changes in QoL domains and reduction in PD symptomatology at follow up. A further important shortcoming is the relatively small sample size, which prevented us from conducting subgroup analyses. For instance, it would have been interesting to look more thoroughly into the role of comorbid disorders and concomitant medication in the development of QoL. We statistically controlled our analyses for these variables.
Despite these limitations, this study makes a valuable contribution to the important area of research that explores associations between QoL and PD before and after treatment. Although most CBT studies included various symptom assessments (i.e., anticipatory anxiety, panic attacks, phobic avoidance, depressive symptoms), little is known regarding the extent to which patients also experience an improvement in their QoL following treatment. Very few studies employed QoL as an outcome measure for the treatment of patients with PD with CBT. Telch et al.[Reference Telch, Schmidt, Jaimez, Jacquin and Harrington49] assessed QoL in 156 outpatients with PD using the Social Adjustment Scale [Reference Weissman, Prusoff, Thompson, Harding and Myers54] and the Sheehan Disability Scale [Reference Sheehan47]. The results showed that 12 CBGT sessions over an eight-week period were effective in improving QoL. More recently, Heldt et al.[Reference Heldt, Blaya, Isolan, Kipper, Teruchkin and Otto24] examined 32 outpatients with PD refractory to pharmacological treatment with the brief version of the World Health Organization Quality Of Life Instrument (WHO-QOL-bref) . Patients showed substantial improvements in all domains of QoL following 12 CBGT sessions over four months. A further study by Kiropoulos et al.[Reference Kiropoulos, Klein, Austin, Gilson, Pier and Mitchell30] found significant improvements in QoL, assessed by the WHO-QOL-bref, following both internet-based CBT (N = 46) and face-to-face CBT (N = 40) for PD. The present study is the first that used the SF-36 to assess the outcome of CBGT for PD. Our results provide additional empirical support that:
• patients’ QoL is substantially improved following CBGT;
• symptom improvement comes along with an alleviation in patients’ daily life burden.
In conclusion, our results are encouraging for cognitive-behavior therapists who treat patients suffering from PD in groups, since they indicate that patients’ improvement following CBGT may extend beyond symptom reduction to QoL. However, although patients showed a substantially lower vitality compared to healthy subjects at baseline, this aspect of QoL did not improve following CBGT. If replicated in controlled studies, this finding would suggest that additional interventions designed to enhance well-being are required. Furthermore, it appears to be recommendable that future clinical trials of PD should include comprehensive measures of QoL in addition to symptom severity scales.