Clinical characteristics and treatment outcomes of patients with major depressive disorder and comorbid anxiety disorders - results from a European multicenter study

This naturalistic European multicenter study aimed to elucidate the association between major depressive disorder (MDD) and comorbid anxiety disorders. Demographic and clinical information of 1346 MDD patients were compared between those with and without concurrent anxiety disorders. The association between explanatory variables and the presence of comorbid anxiety disorders was examined using binary logistic regression analyses. 286 (21.2%) of the participants exhibited comorbid anxiety disorders, 10.8% generalized anxiety disorder (GAD), 8.3% panic disorder, 8.1% agoraphobia, and 3.3% social phobia. MDD patients with comorbid anxiety disorders were characterized by younger age (social phobia), outpatient status (agoraphobia), suicide risk (any anxiety disorder, panic disorder, agoraphobia, social phobia), higher depressive symptom severity (GAD), polypsychopharmacy (panic disorder, agoraphobia), and a higher proportion receiving augmentation treatment with benzodiazepines (any anxiety disorder, GAD, panic disorder, agoraphobia, social phobia) and pregabalin (any anxiety disorder, GAD, panic disorder). The results in terms of treatment response were conflicting (better response for panic disorder and poorer for GAD). The logistic regression analyses revealed younger age (any anxiety disorder, social phobia), outpatient status (agoraphobia), suicide risk (agoraphobia), severe depressive symptoms (any anxiety disorder, GAD, social phobia), poorer treatment response (GAD), and increased administration of benzodiazepines (any anxiety disorder, agoraphobia, social phobia) and pregabalin (any anxiety disorder, GAD, panic disorder) to be associated with comorbid anxiety disorders. Our findings suggest that the various anxiety disorders subtypes display divergent clinical characteristics and are associated with different variables. Especially comorbid GAD appears to be characterized by high symptom severity and poor treatment response.     

Panic and phobic anxiety: associations among neuroticism, physiological hyperarousal, anxiety sensitivity, and three phobias

A dimensional and psychometrically informed taxonomy of anxiety is emerging, but the specific and nonspecific dimensions of panic and phobic anxiety require greater clarification. In this study, confirmatory factor analyses of data from a sample of 438 college students were used to validate a model of panic and phobic anxiety with six content factors; multiple scales from self-report measures were indicators of each model component. The model included a nonspecific component of (1) neuroticism and two specific components of panic attack, (2) physiological hyperarousal, and (3) anxiety sensitivity. The model also included three phobia components of (4) classically defined agoraphobia, (5) social phobia, and (6) blood-injection phobia. In these data, agoraphobia correlated more strongly with both the social phobia and blood phobia components than with either the physiological hyperarousal or the anxiety sensitivity components. These findings suggest that the association between panic attacks and agoraphobia warrants greater attention.     

Agoraphobia with panic attacks. Development, diagnostic stability, and course of illness

A structured psychiatric interview was used to examine the symptom history of 55 patients meeting DSM-III criteria for agoraphobia with panic attacks and five patients meeting DSM-III criteria for panic disorder. Anticipatory anxiety and generalized anxiety occurred in over 80% of the patients, and these anxiety states together with panic attacks and phobic avoidances had courses that were chronic and unremitting. Major depression occurred in 70% of the patients and had an episodic course that differentiated it from the anxiety states. Other frequently reported disorders were childhood separation disorder (18%), alcoholism (17%), and obsessive compulsive disorder (17%). An initial nonspontaneous first panic attack and separation anxiety was associated with earlier onset and longer duration of agoraphobia and panic disorder. An inaccurate cognitive appraisal of the initial panic attack frequently led to the rapid development of subsequent agoraphobia. Caffeine consumption exacerbated anxiety in 54% of the patients and triggered panic attacks in 17%. Fifty-one percent of female agoraphobics experienced premenstrual exacerbation of anxiety symptoms.     

Childhood separation anxiety and panic disorder: a comparative study

1. The relationship between childhood separation anxiety and panic disorder in adults is analyzed using data from a multicenter trial in 107 patients. 2. The patients included in this study presented anxiety disorder with or without agoraphobia, diagnosed according to DSM-III criteria. 3. The percentage of patients with antecedents of separation anxiety was 17.8% in patients without agoraphobia and 21.7% in patients with agoraphobia. These rates are significantly higher than those encountered in a group of normal controls (4%). 4. The existence of separation anxiety in childhood does not seem to significantly modify the clinical manifestations or severity of panic disorder in the adult.     

Correlates of DSM-III personality disorder in panic disorder and agoraphobia

One hundred eighty-seven patients meeting DSM-III criteria for panic disorder (n = 26) or agoraphobia with panic (n = 161) were assessed with the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess Axis II personality disorders and traits. Results replicated our earlier findings of a preponderance of dependent, avoidant, and histrionic features and the finding that patients exhibiting a greater number of personality traits were also significantly more symptomatic. Patients with the diagnosis of panic disorder did not differ on any personality disorder variables from patients with the diagnosis of agoraphobia with panic. Furthermore, none of the specific symptom dimensions, i.e., panic, anxiety, or agoraphobia, was selected as a unique predictor of any personality variables in the regression analyses. Rather, the most important correlates of personality disorder in these patients consisted of general factors such as dysphoric mood, social phobia, or interpersonal sensitivity, and Eysenck's neuroticism dimension. The results are discussed in light of recent findings suggesting a nonspecific link between panic disorder or agoraphobia and personality disorder.     

Is childhood separation anxiety disorder a predictor of adult panic disorder and agoraphobia? A seven-year longitudinal study

OBJECTIVE: To examine whether separation anxiety disorder (SAD) in childhood is a risk factor for panic disorder and agoraphobia in adulthood. METHOD: Patients (n = 85) who had completed treatment for SAD, generalized anxiety disorder, and/or social phobia 7.42 years earlier (on average) were reassessed using structured diagnostic interviews. RESULTS: Subjects with a childhood diagnosis of SAD did not display a greater risk for developing panic disorder and agoraphobia in young adulthood than those with other childhood anxiety diagnoses. Subjects with a childhood diagnosis of SAD did not more frequently meet full diagnostic criteria for panic disorder and agoraphobia, generalized anxiety disorder, social phobia, or major depressive disorder in adulthood than subjects with childhood diagnoses of generalized anxiety disorder or social phobia, but were more likely to meet criteria for other anxiety disorders (i.e., specific phobia, obsessive compulsive disorder, posttraumatic stress disorder, and acute stress disorder). CONCLUSIONS: These results argue against the hypothesis that childhood SAD is a specific risk factor for adult panic disorder and agoraphobia.     

Thyroid hormones in panic disorder, panic disorder with agoraphobia, and generalized anxiety disorder

Fifty-two patients with generalized anxiety disorder who had symptoms persisting for at least 6 months, 41 patients suffering from either panic disorder (32 patients) or panic disorder with agoraphobia (9 patients), and 14 control subjects were screened for thyroid disease. Total serum thyroxine (TT4), serum-free thyroxine index (FT4I), and triiodothyronine resin uptake (T3RU), were examined for the entire sample, using a one-way analysis of variance (ANOVA). No significant differences were found in TT4 (p = .24), FT4I (p = .24), and T3RU (p = .19). Thyroid-stimulating hormone (TSH) was examined in a subsample of 10 patients with generalized anxiety disorder, 11 with panic disorder or panic disorder with agoraphobia, and 10 controls. One-way ANOVA again showed no significant differences, although there was a trend (p = .07). This is the first report that compares generalized anxiety disorder patients, panic disorder patients, and patients with panic disorder and agoraphobia with controls on measures of thyroid function. It is also the first to report normal values in the thyroid indices of generalized anxiety disorder patients.     

Childhood and family characteristics in panic and generalized anxiety disorders

The author compared 32 patients who had generalized anxiety disorders with 29 patients who had panic disorder and agoraphobia with panic attacks. He observed that patients with generalized anxiety disorder more often had lost their fathers and/or mothers before the age of 16 years, whereas patients with panic disorder and agoraphobia with panic attacks had more often experienced chronic anxiety in childhood. More parents and siblings of patients with panic disorder had affective disorders and alcohol abuse than did parents and siblings of patients with anxiety disorders.     

Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study

Objectives: Growing evidence indicates that inflammatory processes may play a role in the pathogenesis of anxiety disorders. Nevertheless, much remains to be learned about the involvement of inflammation, including C-reactive protein (CRP), in specific anxiety disorders. This study examines the relation between anxiety disorders and CRP.

Methods: Associations of serum CRP with anxiety disorders were determined in a large population study (n?=?54,326 participants, mean age?=?47 years; 59% female), the LifeLines cohort. Depressive and anxiety disorders (generalized anxiety disorder, social anxiety phobia, panic disorder with or without agoraphobia and agoraphobia without panic disorder) were assessed using the Mini-International Neuropsychiatric Interview.

Results: Anxiety disorders, with the exception of social anxiety disorder, were significantly associated with increased CRP. After adjusting for demographics, life style factors, health factors, medication use, depression, and psychological stressors, CRP remained significantly associated with panic disorder with agoraphobia (β?=?0.01, P?=?.013). Moreover, CRP levels were significantly higher in people with panic disorder with agoraphobia compared to other anxiety disorders, independent of all covariates (F?=?3.00, df?=?4, P?=?.021).

Conclusions: Panic disorder with agoraphobia is associated with increased CRP, although the effect size of this association is small. This indicates that neuroinflammatory mechanisms may play a potential role in its pathophysiology.     

Comparing panic disorder uncomplicated and panic disorder with agoraphobia in cardiology patients with atypical or nonanginal chest pain

Thirty-eight cardiology patients with either atypical or nonanginal chest pain and current panic disorder were divided into two groups, those with agoraphobia (N = 8) and those without agoraphobia (N = 30). The agoraphobia group reported marginally longer duration of panic disorder (17.0 ± 21.1 years vs. 3.0 ± 3.2 years) and significantly more panic symptoms (10.6 ± 3 vs. 7.3 ± 2.2) during the last major attack. The agoraphobia group also scored significantly higher on measures of anxiety, depression, phobic avoidance, somatization, interpersonal sensitivity, and psychoticism and also scored higher on three of three global measures of distress. This agoraphobia group differed from previously reported agoraphobics with panic attacks in that they all had current panic disorder, while previously reported groups were categorized according to DSM-III, which required only a history of panic attacks. These findings suggest that patients who have current panic disorder and agoraphobia are more symptomatic. Of interest is the low proportion of agoraphobics compared to nonagoraphobics found in this panic disorder population.     

Diverse Profiles of Anxiety Related Disorders in Fragile X,Cornelia de Lange and Rubinstein–Taybi Syndromes

Anxiety disorders are heightened in specific genetic syndromes in comparison to intellectual disability of heterogeneous aetiology. In this study, we described and contrasted anxiety symptomatology in fragile X (FXS), Cornelia de Lange (CdLS) and Rubinstein–Taybi syndromes (RTS), and compared the symptomatology to normative data for typically-developing children and children diagnosed with an anxiety disorder. Scores did not differ between children diagnosed with an anxiety disorder and (a) participants with FXS on social phobia, panic/agoraphobia, physical injury fears, and obsessive–compulsive subscales (b) participants with CdLS on separation anxiety, generalized anxiety, panic/agoraphobia, physical injury fears and obsessive–compulsive subscales, and (c) participants with RTS on panic/agoraphobia and obsessive–compulsive subscales. The results highlight divergent profiles of anxiety symptomatology between these groups.     

Panic attacks. A review of treatments and pathogenesis

In the psychiatric literature, panic attacks have been considered as part of the clinical manifestations of anxiety neurosis, agoraphobia, functional cardiovascular disturbances, and the phobic depersonalization syndrome. Even though recurrent spontaneous panic attacks are described in these entities, the importance ascribed to them has been minor one. Therefore, panic attacks are poorly understood from a psycho-physio pathological point of view. In the past years, new trends in the nosology of psychiatric disorders have grouped the recurrent spontaneous panic attacks under the heading "panic disorder and agoraphobia with panic attacks." In this view, we present the results of the controlled pharmacological trials on patients complaining of panic attacks. Some relationships between panic attacks, panic disorder, and agoraphobia are discussed.     

An examination of syndromal validity and diagnostic subtypes in social phobia and panic disorder.

BACKGROUND: We investigated whether patients with DSM-III-R panic disorder and patients with social phobia could be distinguished on the basis of selected demographic variables and by several commonly used anxiety and phobia rating scales. METHOD: Sixty-six patients with social phobia and 60 patients with panic disorder (42 with and 18 without agoraphobia) were studied. Subjects completed a battery of self-report measures that assessed phobic fears, avoidance, and related problems. RESULTS: Social phobic patients showed an earlier age at onset than the panic disorder group, and there was a trend for more social phobics to have never married. Social phobics reported significantly greater levels of social phobic avoidance and distress, fear of negative evaluation, and avoidance of social situations than the panic disorder patients who reported more overall anxiety and rated themselves as significantly more avoidant of situations involving exposure to public places and to blood or injury. Discriminant function analyses showed that social phobic and panic disorder patients can be reliably discriminated on these scales. CONCLUSION: The results of this study lend further support for the validity of the DSM-III-R nosologic distinctions between social phobia and panic disorder. Furthermore, generalized social phobia appears to be remarkably different from discrete social phobia on these measures. This study provides less support for considering panic disorder with agoraphobia to be distinct from panic disorder without agoraphobia.     

Examination of the utility of the Beck Anxiety Inventory and its factors as a screener for anxiety disorders

The Beck Anxiety Inventory (BAI) and the Anxiety Disorders Interview Schedule (ADIS-IV) were administered to 193 adults at a major Midwestern university recruited from an anxiety research and treatment center. The BAI and its four factor scores were compared from individuals with a primary diagnosis of generalized anxiety disorder (GAD), specific or social phobia, panic disorder with or without agoraphobia, obsessive-compulsive disorder (OCD), and no psychiatric diagnosis. The cut scores on the BAI and its factors, their sensitivity, specificity, as well as positive and negative predictive values were calculated for each group. The results of this study support previous findings that the strongest quality of the BAI is its ability to assess panic symptomatology. The present study also expands on this notion by establishing that the BAI can be used as an efficient screening tool for distinguishing between individuals with and without panic disorder.     

The diagnosis and management of panic disorder

The diagnosis of panic disorder without agoraphobia can very often be quite difficult because of the similarity with physical disorders particularly in the cardiac, gastrointestinal or neurological systems. The distinction must be made between panic attacks appearing as medical problems and medical problems appearing as panic attacks. Sometimes the diagnosis of panic attacks is made only after the medical diagnoses have been excluded. Panic disorder with agoraphobia however is much easier to detect if one carefully traces the historical development of agoraphobia and carefully distinguishes between the anxiety produced by agoraphobia and the panic attacks related to panic disorder. Panic disorder must also be distinguished from other anxiety disorders since the treatment for panic disorder still is quite specific. Once diagnosed however, the treatment of panic disorder without agoraphobia is rather simple. It involves the use of a benzodiazepine, either alprazolam or clonazopam, and perhaps the concomitant use of either imipramine or phenelzine sulfate for the rapid control of anxiety symptoms and continued treatment of the disorder. It is also very helpful to have the patient in psychotherapy either using a supportive or cognitive approach. If the patient has a panic disorder with agoraphobia, the pharmacological approach is the same, with the initiation of treatment using either alprazolam or clonazopam, but the psychotherapeutic approach is somewhat different in that behavioral therapy is emphasized rather than purely supportive or cognitive approaches. Given the fact that 1%-2% of the population is at risk for panic disorder, it is important that the condition be rapidly recognized and treated effectively since the currently available modalities of treatment result in almost total resolution of symptoms. Some individuals will remain on medication for several years while others will find it possible to decrease and/or discontinue their medications after only a few months or a few years. There is little excuse at this point for this disorder to be ineffectively diagnosed or treated.     

Paths to panic disorder/agoraphobia: an exploratory analysis from age 3 to 21 in an unselected birth cohort

OBJECTIVE: To evaluate childhood temperamental traits and early illness experiences in the etiology of adult panic disorder with agoraphobia. METHOD: Evaluated temperamental and illness experience factors, at ages 3 through 18, as predictors of panic and agoraphobia at ages 18 or 21 in an unselected sample (N = 992). Analyses were conducted with classification trees. RESULTS: Experience with respiratory ill health predicted panic/agoraphobia relative to other anxiety disorders and healthy controls. Also, temperamental emotional reactivity at age 3 predicted panic/agoraphobia in males but did not predict other anxiety disorders, compared with healthy controls. Furthermore, temperament and ill health interacted with gender. CONCLUSIONS: Results are discussed in terms of cognitive theories of fear of physical symptoms and biological models of respiratory disturbance for panic/agoraphobia.     

The symptom structure of panic disorder: a trial using factor and cluster analysis

Using cluster analysis of 207 patients with panic disorder (PD), we investigated the relationships between several panic symptoms at the time of panic attacks, which included anticipatory anxiety, agoraphobia, and 13 clinical symptoms based on the Diagnostic and Statistics Manual-III-Revised. Cluster analysis revealed three panic symptom clusters: cluster A (dyspnea, choking, sweating, nausea, flushes/chills); cluster B (dizziness, palpitations, trembling or shaking, depersonalization, agoraphobia, and anticipatory anxiety); and cluster C (fear of dying, fear of going crazy, paresthesias, and chest pain or discomfort). Generally, cluster A was comprised exclusively of physiological symptoms, among which respiratory symptoms were prominent, cluster B included both panic and non-panic symptoms such as agoraphobia and anticipatory anxiety, and cluster C was comprised chiefly of fear symptoms.     

Patterns of comorbidity in panic disorder and agoraphobia.

Diagnoses of comorbid disorders were determined in a sample of 54 patients with panic disorder as defined in DSM-III-R. The sample was divided into the following three groups: (1) uncomplicated panic disorder (PDU); (2) panic disorder with mild agoraphobia (PDM); and (3) panic disorder with moderate to severe agoraphobia (PDA). In comparison with patients with PDU, patients with PDA had higher comorbidity rates in general, received multiple comorbid diagnoses more frequently, had a higher prevalence of major depression, dysthymia, social phobia, generalized anxiety disorder, and obsessive-compulsive disorder, and scored higher on most measures of self-rated psychopathology. These findings support the notion that PDA may be a disorder essentially different from PDU.     

DSM-III-R Axis I and II disorders in agoraphobic patients with and without panic disorder

Patients attending an inpatient phobia treatment program were diagnosed for DSM-III-R Axis I and II disorders, using the Structured Clinical Interview for DSM-III-R Disorders, and completed a set of self-report instruments. They were divided into 3 groups: (a) those who met the criteria for panic disorder with agoraphobia (n= 57), (b) those who met the criteria for agoraphobia without a history of panic disorder (n= 21), and (c) those who met criteria for other anxiety disorders, but not for panic/agoraphobia (n= 14). On Axis I, more of the panic with agoraphobia than of the agoraphobia without panic patients had obsessive-compulsive disorder. On Axis II, no significant differences between the agoraphobic patients with and without panic occurred. However, the number of hysterical traits was related to the presence of panic disorder among the agoraphobic patients. Avoidant and dependent traits were related to symptom severity.