Panikstörung und Agoraphobie sind häufig auftretende Angststörungen, die mit einer hohen individuellen aber auch gesellschaftlichen Belastung einhergehen. Es existieren sehr erfolgreiche, aber auch aufwändige Behandlungsmethoden. Trotz einer hohen Erfolgsquote dieser Behandlungen kommt es immer wieder zu einer nicht ausreichenden Verbesserung der Beschwerden oder auch Therapieabbrüchen. Zu möglichen Einflussfaktoren auf den Therapieerfolg, -misserfolg oder Abbrüche wurde bereits mit widersprüchlichen Ergebnissen geforscht. Es erscheint sinnvoll, diese Faktoren zu kennen, um Fehlindikationen in ein aufwändiges Therapieverfahren zu vermeiden und den Leidensdruck der Patient:innen gegebenenfalls mit einem anderen Verfahren schneller zu lindern. Die vorliegende Arbeit untersucht, ob solche Prädiktoren für den Nicht-Erfolg im Kontext eines naturalistischen Behandlungssettings in der Angst-Tagesklinik an der Klinik und Poliklinik für Psychotherapie und Psychosomatik des Universitätsklinikums Carl Gustav Carus identifiziert werden können. Dazu wurde der Therapieeffekt anhand 214 Patient:innen geprüft. Weiterhin wurden sie hinsichtlich demografischer, sozialmedizinischer und störungsspezifischer Kennwerte am Anfang und am Ende der Behandlung untersucht und am Grad der Veränderung angstspezifischer Kennwerte in Responder und Non-Responder unterteilt. Anschließend wurden über logistische Regressionen Faktoren für die Non-Response identifiziert. Es stellte sich heraus, dass die Behandlung einen mittleren bis großen Effekt auf verschiedene Störungsmaße aufwies, jedoch ca. 57,5% der Patient:innen keine oder eine im klinischen Sinne unzureichende Verbesserung erlebt hatten. Dabei zeigte sich, dass sich die Betrachtung des Familienstands, des Ausmaßes der Angst vor körperlichen Krisen und die Mobilitätsvermeidung ohne Begleitperson gemeinsam am besten eignen, um eine mögliche Non-Response vorherzusagen. Das errechnete Modell fällte dabei auf Basis der Aufnahmedaten in 62,8% der Fälle die korrekte Entscheidung zur Zuordnung in die Gruppen der Responder und Non-Responder. Somit ist das Modell leider nicht ausreichend, um zweifelsfrei im Vorfeld einer Behandlung individuell zu entscheiden, ob die angebotene Expositionsbehandlung zielführend ist oder nicht. Das Modell gibt allerdings wichtige Hinweise auf mögliche Einflussfaktoren auf die Eignung zur Behandlung, auch wenn weitere, nicht untersuchte oder nicht messbare Faktoren bedeutsam sein könnten. / Panic disorder and agoraphobia are common anxiety disorders that are associated with a high individual burden, but also social burden. There are very successful, but also costly treatment methods. Despite a high success rate of these treatments, there sometimes is an insufficient reduction of symptoms or even therapy discontinuation in individual patients. Research has already been done on possible factors influencing the success, failure or discontinuation of therapy, with contradictory results. It makes sense to know these factors in order to avoid wrong indications for a complex therapy procedure and to alleviate the patients' suffering more quickly with another procedure. This study investigates whether such predictors of non-response can be identified in the context of a naturalistic treatment setting in the Angst-Tagesklinik at the Klinik und Poliklinik für Psychotherapie und Psychosomatik of the University Hospital Carl Gustav Carus Dresden. For this purpose, the therapy’s effect was tested on 214 patients. Furthermore, they were examined with regard to demographic, socio-medical and disorder-specific parameters at the beginning and end of treatment and divided into responders and non-responders according to the degree of change in anxiety-specific parameters. Subsequently, logistic regressions were used to identify factors for non-response. It was found that the treatment had a medium to large effect on various disorder specific measures, but that about 57.5% of the patients had experienced no improvement or insufficient improvement in the clinical sense. It was found that looking at marital status, level of fear of physical crises and mobility avoidance without a companion were best suited to predict a possible non-response to the treatment. Based on the patients’ admission data, the calculated predictor model made the correct decision to assign the patient to the responder and non-responder groups in 62,8% of the cases. In conclusion, the model is not sufficient to predict, whether the exposure treatment will be successful or not. However, the model provides important indications of possible factors influencing the suitability for treatment, even though other factors that have not been investigated or that are not measurable could be significant.

Le but de cette étude est d'identifier les facteurs cognitifs permettant d'expliquer le niveau d'appréhension de l'apparition d'une attaque de panique. Quarante-quatre femmes et 15 hommes (âge moyen de 37.9 ans) souffrant de trouble panique avec agoraphobie (TPA) y ont participé. L'étude comprend un traitement cognitivo- comportemental pour le TRA et deux périodes d'auto-enregistrement de 5 semaines avant et après le traitement. Les résultats révèlent la présence de deux construits parmi les facteurs. Le premier comprend les croyances dysfonctionnelles, la perception de menace et la probabilité d'avoir une attaque de panique; le second, la perception de contrôle et d'efficacité personnelle. Le premier construit est le meilleur prédicteur du niveau d'appréhension en pré-traitement et permet de distinguer les participants qui n'ont plus d'appréhension de ceux à qui il en reste en post-traitement. Les résultats sont discutés en fonction des mécanismes thérapeutiques en jeu dans le traitement du TRA avec agoraphobie.

Cette thèse de doctorat vise à répondre à deux questions de recherche auprès de personnes souffrant du trouble panique avec agoraphobie. Premièrement, est-ce qu'il y a une différence dans la rapidité avec laquelle l'exposition et la restructuration cognitive produisent des gains significatifs? Deuxièmement, quel est le mécanisme thérapeutique sous-jacent à ces deux stratégies cognitivo-comportementales? Après avoir fait état des modèles théoriques expliquant l'étiologie et le maintien du trouble panique, les résultats de deux études empiriques sont rapportés. L'objectif de la première étude est d'évaluer, auprès des personnes souffrant d'un trouble panique avec agoraphobie, les différences dans la rapidité avec laquelle l'exposition et la restructuration cognitive produisent des changements sur les variables cliniques, comportementales et cognitives. Vingt-huit sujets recevant un diagnostic de trouble panique avec agoraphobie sont assignés aléatoirement à l'une des deux conditions expérimentales suivantes: Exposition ou Restructuration Cognitive. Les sujets sont évalués à quatre reprises, soit: lors du prétraitement, après 5, 10 et 15 (posttraitement) semaines de traitement. La seconde étude vise à démontrer que les changements dans l'intensité des croyances précèdent les changements du niveau d'appréhension d'une attaque de panique. Deux variables sont mesurées quotidiennement, soit: la force de la principale croyance que chaque sujet entretient envers les attaques de panique, et le niveau d'appréhension d'une attaque de panique. Les ANOVAs indiquent la présence d'un effet "Temps" statistiquement significatif et important pour l'ensemble des instruments de mesure. Toutefois, aucun effet d'interaction "Groupe par Temps" n'est significatif. Ces résultats et des analyses de puissance statistique suggèrent que l'exposition et la restructuration cognitive sont à toutes fin pratique d'une rapidité comparable. Un plus grand nombre de sujets s'avère nécessaire pour confirmer ces résultats. Parmi les sujets qui ne ressentent plus aucune attaque de panique à la fin de ces interventions thérapeutiques, des analyses de séries chronologiques multivariées et des tests de causalité permettent de conclure que les changements de croyance précèdent la réduction du niveau d'appréhension d'une attaque de panique pour 75% d'entre eux. Le mécanisme thérapeutique de l'exposition et de la restructuration cognitive s'avère donc similaire: a savoir la modification des croyances. / The aim of this doctoral thesis is to answer two research questions among people suffering from panic disorder with agoraphobia. First, is there a difference in the rate of change between exposure and cognitive restructuring? Second, what is the treatment mechanism operating during exposure and cognitive restructuring? After describing the etiological and maintaining model of panic disorder, results of two empirical studies are described. The aim of the first study was to assess the rate of change on clinical, behavioral and cognitive variables during exposure and cognitive restructuring in the treatment of panic disorder with agoraphobia. A total of 28 subjects who received a diagnosis of panic disorder with agoraphobia were randomly assigned to either of two treatment conditions: Exposure orCognitive Restructuring. Subjects were assessed on four occasions: pretreatment, after 5, 10,and 15 (post-treatment) weeks of treatment. The aim of the second study was to demonstrate that changes in beliefs precede changesin apprehension of a panic attack. Two variables were measured: the strength of each subject'smain beliefs toward the consequence of a panic attack, and the level of apprehension of a panic attack. ANOVAs revealed strong and statistically significant Time effect on all measures. However, no Group X Time interaction reached statistical significance. Furthermore, power analyses sugest that any difference that might exist in the rate of improvement between exposure and cognitive restructuring in the treatment of panic disorder with agoraphobia is marginal. More subjects are needed to confirm these results. However, no Group X Time interaction reached statistical significance. Furthermore, power analyses sugest that any difference that might exist in the rate of improvement between exposure and cognitive restructuring in the treatment of panic disorder with agoraphobia is marginal. More subjects are needed to confirm these results. Multivariate time series analysis and causality testing showed that, for 75% of the subjects who were panic-free at post-treatment, changes in beliefs preceded improvement. Thus, it would seem that the modification of beliefs is involved in the therapeutic mechanism of both exposure and cognitive restructuring.

Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview – Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14–24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0–23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity) as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies.

Background: The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). Methods: Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. Results: Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. Conclusions: We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder.

Theoretischer Hintergrund: Die Rolle der Therapeutenbegleitung während Expositionsübungen bei Panikstörung mit Agoraphobie (P/A) ist bislang ungeklärt. Eine kürzlich durchgeführte klinische Studie (MAC-Studie) lieferte Hinweise auf ein günstigeres Behandlungsergebnis bei Therapeutenbegleitung. Fragestellung: Wie lassen sich Effekte therapeutenbegleiteter Exposition (T+) im Vergleich zu Exposition ohne Therapeutenbegleitung (T–) erklären? Methode: Daten von 301 Patienten, die eine expositionsbasierte KVT mit bzw. ohne Therapeutenbegleitung erhalten hatten, wurden analysiert. Untersucht wurden der Einfluss der initialen Störungsschwere, des Sicherheitsverhaltens sowie differenzielle Effekte der Bedingungen auf die Angst vor der Angst. Zusätzlich wurde überprüft, inwieweit die Übungshäufigkeit in den Behandlungsbedingungen variiert und einen Mediator des Behandlungserfolgs darstellt. Ergebnisse: Störungsschwere und Sicherheitsverhalten zeigten keine differenziellen Effekte zwischen den Bedingungen; die T+ Bedingung führte jedoch zu stärkeren Reduktionen der Angst vor der Angst im Angstsensitivitätsindex. Patienten der T+ Bedingung führten häufiger selbständig Expositionsübungen durch, während Patienten in T– im Durchschnitt länger übten. Die Übungshäufigkeit stellte dabei einen Mediator des Behandlungserfolgs dar. Schlussfolgerungen: Günstigere Effekte einer therapeutenbegleiteten Exposition gehen auf stärkere Reduktionen der Angst vor der Angst sowie auf eine höhere Übungshäufigkeit im Selbstmanagement zurück. / Theoretical background: There is a paucity of studies examining the role of therapist guidance during in-vivo exposure for panic disorder with agoraphobia (PD/AG). A recent study (MAC-study) suggested superior effects of therapist-guided exposure compared to programmed practice. Objectives: Examining potential mechanisms of therapist-guided exposure. Methods: Data from 301 patients with PD/AG who received either CBT with therapist guidance during in-vivo exposure (T+), or CBT with programmed exposure practice (T–) were analysed in regard to effects of initial symptom severity, subtle avoidance behaviours, reductions in fear of fear, and frequency of exposure homework. Results: There were no interaction effects between symptom severity or subtle avoidance and outcome. T+ was associated with higher reductions in fear of fear as well as with higher frequency of exposure homework. Frequency of exposure homework mediated the effect of group on outcome. Conclusion: Advantages of therapist-guided exposure as well as frequency of self-exposure might be attributed to higher reductions in fear of fear.

Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview – Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14–24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0–23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity) as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies.

A literature search, in addition to expert survey, was performed to estimate the size and burden of panic disorder in the European Union (EU). Epidemiologic data from EU countries were critically reviewed to determine the consistency of prevalence estimates across studies and to identify the most pressing questions for future research. A comprehensive literature search focusing on epidemiological studies in community and clinical settings in European countries since 1980 was conducted (Medline, Web of Science, Psychinfo). Only studies using established diagnostic instruments on the basis of DSM-III-R or DSM-IV, or ICD-10 were considered. Thirteen studies from a total of 14 countries were identified. Epidemiological findings are relatively consistent across the EU. The 12-month prevalence of panic disorder and agoraphobia without history of panic were estimated to be 1.8% (0.7–2.2) and 1.3% (0.7–2.0) respectively across studies. Rates are twice as high in females and age of first onset for both disorders is in adolescence or early adulthood. In addition to comorbidity with agoraphobia, panic disorder is strongly associated with other anxiety disorders, and a wide range of somatoform, affective and substance use disorders. Even subclinical forms of panic disorder (i.e., panic attacks) are associated with substantial distress, psychiatric comorbidity and functional impairment. In general health primary care settings, there appears to be substantial underdiagnosis and undertreatment of panic disorder. Moreover, panic disorder and agoraphobia are poorly recognized and rarely treated in mental health settings, despite high health care utilization rates and substantial long-term disability.

Cognitive behavioral therapy (CBT) is efficacious for panic disorder with agoraphobia (PD/A). Nevertheless, the active ingredients of treatment and the mechanisms through which CBT achieves its effects remain largely unknown. The mechanisms of action in CBT (MAC) study was established to investigate these questions in 369 patients diagnosed with PD/A. The MAC study utilized a multi-center, randomized controlled design, with two active treatment conditions in which the administration of exposure was varied, and a wait-list control group. The special feature of MAC is the way in which imbedded experimental, psychophysiological, and neurobiological paradigms were included to elucidate therapeutic and psychopathological processes. This paper describes the aims and goals of the MAC study and the methods utilized to achieve them. All aspects of the research design (e.g., assessments, treatment, experimental procedures) were implemented so as to facilitate the detection of active therapeutic components, and the mediators and moderators of therapeutic change. To this end, clinical, behavioral, physiological, experimental, and genetic data were collected and will be integrated.

Although functional magnetic resonance imaging (fMRI) has gained increasing importance in investigating neural substrates of anxiety disorders, less is known about the stress eliciting properties of the scanner environment itself. The aim of the study was to investigate feasibility, self-reported distress and anxiety management strategies during an fMRI experiment in a comprehensive sample of patients with panic disorder and agoraphobia (PD/AG). Within the national research network PANIC-NET, n = 89 patients and n = 90 controls participated in a multicenter fMRI study. Subjects completed a retrospective questionnaire on self-reported distress, including a habituation profile and exploratory questions about helpful strategies. Drop-out rates and fMRI quality parameters were employed as markers of study feasibility. Different anxiety measures were used to identify patients particularly vulnerable to increased scanner anxiety and impaired data quality. Three (3.5%) patients terminated the session prematurely. While drop-out rates were comparable for patients and controls, data quality was moderately impaired in patients. Distress was significantly elevated in patients compared to controls; claustrophobic anxiety was furthermore associated with pronounced distress and lower fMRI data quality in patients. Patients reported helpful strategies, including motivational factors and cognitive coping strategies. The feasibility of large-scale fMRI studies on PD/AG patients could be proved. Study designs should nevertheless acknowledge that the MRI setting may enhance stress reactions. Future studies are needed to investigate the relationship between self-reported distress and fMRI data in patient groups that are subject to neuroimaging research.