Differences in symptom structure between panic attack and limited symptom panic attack: A study using cluster analysis

Abstract We had investigated the clinical characteristics of panic disorder (PD) in a Japanese outpatient population comprised of more than 250 patients diagnosed as having PD during a 13-year study period and observed that some PD patients had both panic attacks (PA) and limited symptom panic attacks (LPA). In the criteria for PD based on the Diagnostic and Statistics Manual of Mental Disorders , third edition-revised ( DSM-III-R ), episodes involving four or more symptoms are classified as PA, while those involving fewer than four symptoms are described as LPA. Therefore, LPA is identified as part of an episode of PA, since the difference between the two episodes is only in the number of symptoms. However, some recent research suggests that there is a distinct subgroup of individuals who suffer LPA. Using cluster analysis, we investigated the differences between PA and LPA groups in terms of the structures of several panic symptoms, which included anticipatory anxiety, agoraphobia and 13 clinical symptoms based on the DSM-III-R at the time of panic attacks, in 247 patients with PD. Cluster analysis revealed clusters of three and four panic symptoms in the PA group and LPA group, respectively, and there were also differences in symptom structure between the two groups. These results suggest that there may be a subgroup of individuals who show LPA among PD patients.     

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.     

Assessing the clinical utility of agoraphobia in the context of panic disorder

In the DSM-IV, a panic disorder (PD) diagnosis includes specification of agoraphobia, which is primarily an index of situational avoidance due to fear of panic. No other anxiety diagnosis requires specification of level of avoidance. This raises the question as to whether agoraphobia provides unique information beyond the core features of PD (i.e., panic attacks and panic-related worry). The incremental validity of agoraphobia, defined using DSM-IV specifiers versus level of situational avoidance, was examined in relation to the expression and treatment of PD (N=146). Analyses indicate that agoraphobia status adds uniquely to the prediction of PD symptoms, impairment, and response to treatment. However, level of situational avoidance, defined either as a continuous or dichotomous variable, appears to have greater utility compared to the DSM-IV method of classifying agoraphobia. In summary, the agoraphobia specifier seems to have clinical utility but this could be improved by focusing on a dimensional assessment of situational avoidance.     

Four Clinical Types of Panic Disorders

Abstract: The authors attempted to classify panic disorders into four types according to a clinical course and accompanying neurotic or depressive symptoms. The characteristics of each type are as follows; type I: a single panic attack is the only symptom, type 11 : only panic attacks occur frequently without any accompanying neurotic or depressive symptoms, type III: a recurrence of panic attacks and the gradual development of neurotic symptoms, such as anticipatory anxiety, generalized anxiety, agoraphobia, or hypo-chondriasis, type IV: depressive symptoms develop in the course of recurring panic attacks. Type IV is further divided into three subtypes. Type IV- 1 : depressive symptoms develop secondary to panic attacks and major depression later coexists with panic disorder. Type IV- 2 : panic disorder continuously changed into major depression. Type IV- 3 : panic attacks and depressive symptoms are seen independently. The most common types are type III and type IV-1, and seem to be a core group of the panic disorder. Typical cases of each type are presented and underlying psychopathology is discussed.     

Four cases of panic disorder successfully treated with Kampo (Japanese herbal) medicines: Kami-shoyo-san and Hange-koboku-to

Kampo medicines have been used to treat patients with psychogenic disorders from ancient times. In the present report the cases are described of four patients with panic disorder successfully treated with Kampo medicines. These four patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for panic disorder with agoraphobia. The Kampo medicine Kami-shoyo-san (TJ-24) relieved panic attacks, anticipatory anxiety and agoraphobia in two patients, and Hange-koboku-to (TJ-16) relieved these symptoms in the other two patients. The patients in whom Kami-shoyo-san was effective were older and complained of more symptoms than those in whom Hange-koboku-to was effective. These Kampo medicines may be useful as additional or alternative treatments for panic disorder.     

The latent structure of anxiety symptoms in anxiety disorders.

OBJECTIVE: Research in the psychopathology of panic and anxiety disorders, particularly agoraphobia, suggests that fear of fear may be the basis of these conditions. However, there is little empirical research on the definition and validity of the concept of fear of fear in a clinical study group. The authors' aims are 1) to determine empirically if particular associations between symptoms and beliefs exist in a group of patients with anxiety disorders and what underlying dimensions of perceived threat they represent and 2) to assess the relative importance of these associations in agoraphobia with panic attacks, panic disorder, social phobia, and generalized anxiety disorder. METHOD: In an anxiety disorders treatment unit, 390 outpatients with anxiety disorders diagnosed according to DSM-III criteria completed the Anxiety Symptoms and Beliefs Scale. RESULTS: A principal components analysis of the patients' ratings on the Anxiety Symptoms and Beliefs Scale produced a four-factor solution in which specific sets of anxiety symptoms loaded with specific beliefs. These four factors were interpreted as respiratory symptoms, vestibular symptoms, autonomic arousal, and psychological threat. Respiratory and vestibular symptoms were more associated with panic disorder diagnoses than with social phobia and generalized anxiety disorder diagnoses. CONCLUSIONS: These findings support a conception of fear of fear in anxiety disorders as fearful beliefs concerning the experience of anxiety symptoms. Associations between symptoms and fear of fear are present across anxiety disorders but are most pronounced in agoraphobia with panic attacks.     

Agoraphobia: what Westphal really said.

In 1872 Westphal described a series of patients who experienced unexpected and situational panic attacks in squares, empty streets, on bridges and in crowds. They suffered from anticipatory anxiety and a fear of sudden incapacitation. The symptoms of agoraphobia have not changed appreciably in well over a century.     

Acute panic inventory symptoms during CO(2) inhalation and room-air hyperventilation among panic disorder patients and normal controls.

There is scant literature on anxiety symptoms induced during respiratory challenges developed to induce panic symptoms and attacks. Here we report on the prevalence of Acute Panic Inventory (API) symptoms during three consecutive respiratory challenges to patients with panic disorder (PD) and normal controls (NC). The challenges performed using a closed canopy system included voluntary room air hyperventilation (RAH), inhalation of 5% CO(2), and 7% CO(2)-enriched air. The PD patients were 41 men and 53 women whose mean age was 33.4 (SD = 8.55). The normal comparison group consisted of 35 men and 27 women with a mean age of 31.3 (SD = 9.21). The diagnosis of panic disorder was made using the Structured Clinical Interview for DSM-III-R. All potential normal controls underwent structured clinical interview using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version Modified for the Study of Anxiety Disorders (SADS-LA), and must have been free of a lifetime history of anxiety disorders, affective disorders, substance use disorders, and schizophrenia. All participants also had a complete medical evaluation and were in good health. The experiment consisted of seven experimental epochs: three baseline/recovery periods each followed by a respiratory challenge, and then a final recovery epoch. The API was administered at the end of each epoch. Clinical staff trained and experienced in rating panic attacks rated participants' response during each challenge as panic or no panic. Three groups were defined for analysis: PD patients who panicked, PD patients who did not panic, and NC who did not panic. Staff ratings indicated that the 7% CO(2) challenge was the most panicogenic, followed by the 5% CO(2), and the RAH challenges. Conventional statistics (analysis of variance and partial correlations) indicated that many baseline symptoms as well as symptom increments differed across groups, and were associated with the outcome of panic/no panic during each challenge. However, logistic regression analysis indicated that only a few symptoms independently predicted the panic/no panic outcome because many symptoms were redundant. The symptom cluster of fear in general, dizziness, difficulties with concentrating, and doing one's job predicted panic to RAH. The cluster of fear in general, confusion, dyspnea, and twitching/trembling predicted the response to 5% CO(2). Finally, fear in general, confusion, twitching/ trembling and dizziness predicted the response to 7% CO(2). While univariate analyses indicated that many symptoms distinguished between panic and no panic outcome, logistic regression revealed that group differences were subsumed under a few prominent symptoms, namely, fear in general, confusion, dizziness, twitching/trembling, and dyspnea. The results are discussed in the context of patient (having a diagnosis of PD) and panic effects (rated as panicking to a challenge).     

Convergent and divergent validity of the Beck Anxiety Inventory for patients with panic disorder and agoraphobia

Psychometric properties of the Beck Anxiety Inventory (BAI) (Beck and Steer, 1990) were investigated in a sample of 82 patients suffering from panic disorder with agoraphobia. Before and after brief treatment, patients completed a battery of questionnaires and, for 2-week periods, kept a daily panic diary in which they recorded panic attacks, fear of panic, and average anxiety. The BAI demonstrated excellent internal consistency and good test–retest reliability over a 5-week interval. A partial multitrait, multimethod correlation matrix provided evidence of convergent validity with other measures of anxiety and of divergent validity vis á vis measures of depression. Factor analyses of pretest scores and residual gain scores used to address criticism that the BAI is excessively panic-centric yielded mixed results. In one analysis, the BAI was loaded with multimethod measures of panic and anxiety and, in the other, with questionnaire methods of assessing anxiety and depression. However, the BAI was clearly distinguished from measures of fear of fear, a central construct in panic disorder, and agoraphobic avoidance. Finally, the BAI proved sensitive to change with treatment, yielding effect sizes for improvement comparable to those of other anxiety measures. Depression and Anxiety 6:140–146, 1997. © 1997 Wiley-Liss, Inc.     

Measurement of panic disorder by a modified panic diary

The psychometric characteristics of panic diary measures were investigated in a sample of 37 patients suffering from panic disorder with agoraphobia. Following recommendations made in the recent consensus development conference on the assessment of panic disorder, daily ratings included not only the occurrence of panic attacks but also fear of panic, expectancy of panic, and expected aversiveness of panic. These new measures were reliable and, on the whole, demonstrated good divergent and convergent validity. Further, adding such measures increased the incremental validity of panic disorder assessment. Depression and Anxiety 6:133–139, 1997. © 1997 Wiley-Liss, Inc.     

Health anxiety and fear of fear in panic disorder and agoraphobia vs. social phobia: a prospective longitudinal study

Background: This study is aimed to evaluate the role of two vulnerability factors, health anxiety and fear of fear, in the prediction of the onset of panic disorder/agoraphobia (PDA) relative to a comparison anxiety disorder. Methods: Young women, aged between 18 and 24 years, were investigated at baseline and, 17 months later, using the Anxiety Disorders Interview Schedule‐Lifetime and measures of health anxiety and fear of bodily sensations (subscale disease phobia of the Whiteley Index, and total score of the Body Sensations Questionnaire). First, 22 women with current PDA were compared to 81 women with current social phobia and 1,283 controls. Second, 24 women with an incidence of PDA were compared to 60 women with an incidence of social phobia and 1,036 controls. Results: Multiple logistic regression analyses adjusted for history of physical diseases, somatic symptoms, and other psychological disorders revealed that (a) fear of bodily sensations was elevated for women with PDA vs. controls as well as women with social phobia, and (b) health anxiety (and history of physical diseases) was elevated in women who developed PDA vs. controls and vs. women who developed social phobia. Conclusions: These results suggest that health anxiety, as well as history of physical diseases, may be specific vulnerability factors for the onset of PDA relative to social phobia. Whereas fear of bodily sensations was not found to be a risk factor for the onset of panic disorder/agoraphobia, it was a specific marker of existing PDA relative to social phobia. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Lactate infusions in panic disorder patients and normal controls: autonomic measures and subjective anxiety

The anxiety symptoms, heart rate and blood pressure of 61 patients who panicked during lactate infusions were compared with 25 control nonpanickers. There was no significant difference in the increase in heart rate and blood pressure over baseline between patients and controls. There appeared to be no significant correlation between the subjective anxiety ratings and the measures of heart rate and blood pressure during lactate-induced panic. The symptoms of shortness of breath, feeling frightened or afraid, feeling dizzy and fear of losing control were significantly associated with lactate-induced panic. In addition, the cognitive symptoms of fear of losing control and fear of going crazy appear to be important determinants of lactate-induced panic.     

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 structure of emotional and cognitive anxiety symptoms

A sample of 327 patients with primary panic disorder or social phobia completed a questionnaire comprising 77 emotional and cognitive anxiety symptoms from which 12 index scales were constructed. Explorative factor analysis yielded two factors, but confirmatory factor analysis indicated that the factor solution was not invariant across diagnoses. Nevertheless, the two-factor structures fitting data from patients with panic disorder and social phobia, respectively, had similarities in content. The first factor, emotions and cognitive-social concerns, comprised emotional expressions (sadness, fear, and anger), cognitions about cognitive dysfunction (difficulty concentrating, confusion, and loss of control) and social phobic cognitions. It was positively correlated with severity of bodily anxiety symptoms and with the neuroticism personality trait. The second factor, fear of physical sensations, was positively correlated with a cardio-respiratory dimension of bodily anxiety symptoms in panic disorder, lending support to the hypothesis of specific threat-relevant links between bodily symptoms and catastrophic cognitions.     

Continuous monitoring of panic

Data on naturally occurring panic attacks were gathered through continuous self-monitoring for 94 patients suffering from panic disorder with agoraphobia. A total of 1276 panic attacks were collected. In this article various aspects of panic attacks, including severity, duration and time of onset and situations in which panic occurs are addressed. In addition, the symptoms of panic were investigated, examining the (in)variability of attacks within each patient and the patterning of symptoms in the entire group of patients. The most important findings were as follows: attacks occurred predominantly in nonphobic situations; nocturnal panic attacks were generally more severe than attacks during the day; symptom patterns across various attacks, stemming from the same patient, were rather variable; and finally, a substantial number of the attacks (40%) did not meet the DSM-III-R criteria for number of symptoms.     

Childhood history of anxiety disorders among adults with social phobia: rates, correlates, and comparisons with patients with panic disorder.

We examined the rates and correlates of a childhood history of anxiety disorders in 100 adults with a primary diagnosis of social phobia (social anxiety disorder). Adulthood and childhood disorders were assessed by experienced clinicians with structured clinical interviews. Rates of childhood anxiety disorders were evaluated to diagnostic comorbidity and a comparison group of patients with panic disorder. Onset of social phobia occurred before age 18 in 80% of the sample. Over half of the sample (54%) met criteria for one or more childhood anxiety disorders other than social phobia: 47% for overanxious disorder, 25% for avoidant disorder, 13% for separation anxiety disorder, and 1% for childhood agoraphobia. A history of childhood anxiety was associated with an early age of onset of social phobia, greater severity of fear and avoidance of social situations, greater fears of negative evaluation, and greater anxiety and depression morbidity. Rates of childhood social phobia, overanxious disorder, and avoidant disorder were significantly higher in patients with social phobia relative to our panic-disordered comparison group. We found approximately equal rates of a childhood history of separation anxiety disorder in patients with social phobia and panic disorder, providing further evidence against a unique relationship between separation anxiety disorder and panic disorder.     

Dsm-iv panic attacks and panic disorder in a community sample of adolescents and young adults: how specific are panic attacks?

The study investigates the lifetime and 12-month prevalence, symptoms, age of onset and comorbidity patterns of DSM-IV panic attacks and panic disorder in a community sample of 3021 adolescents and young adults aged 14–24 years. Findings are based on DSM-IV symptoms and diagnoses assessed by interviews using a computerised, extended version of the Munich Composite International Diagnostic Interview (M-CIDI). Lifetime prevalence of DSM-IV panic disorder among 14–24 year-olds was 1.6% (0.8% with and 0.8% without agoraphobia). Panic symptoms were found to be quite frequent (13.1%) in the community, with lifetime prevalence of DSM-IV panic attack at 4.3% (12-month prevalence, 2.7%), with first onset rarely before puberty. Women were considerably more likely to have panic disorder and to have an earlier age of onset than males. Occurrence of DSM-IV panic attacks was strongly related to the subsequent development of various forms of mental disorders—not only panic disorder and agoraphobia. The conditional probability in those with panic attacks to develop other forms of mental disorders was 63% in males and 40% in females. Particularly late onset panic attacks (after the age of 18 years) are associated strongly with the development of multimorbidity of mental disorders. This suggests that panic attacks are generally highly indicative for more severe psychopathology and not only for panic disorder and agoraphobia.     

Three cases of panic disorder with agoraphobia in children

The authors report three cases of panic disorder with agoraphobia in children, with characteristic panic attacks, separation anxiety, and fear and avoidance of crowds and public places. The panic and agoraphobic symptoms responded to medications effective with agoraphobic adults, i.e., imipramine and alprazolam.     

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.     

The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial

BACKGROUND: A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia, the Panic and Agoraphobia Scale (P & A). The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients (panic attacks, avoidance, anticipatory anxiety, disability and worries about health). The application of this scale in a double-blind placebo-controlled panic disorder trial is described. At the same time, the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy. METHODS: Patients with Panic disorder (DSM-IV) were randomly assigned to three treatment modalities: running (n=45), clomipramine (n=15) or placebo (n=15). Treatment efficacy was measured with the Panic and Agoraphobia Scale (P & A) and other rating scales. RESULTS: According to the P & A and other scales, both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment. Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise. The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability. CONCLUSIONS: The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments. Analysis of the scales five subscores may help to understand mechanisms of action of panic disorder treatments.