Psychopathology of panic attacks in panic disorder

PURPOSE: This study examined the relationships among certain subtypes of panic attacks (full vs. limited symptom; spontaneous vs. situational) and between these subtypes, panic disorder subtypes, and other characteristics of panic disorder, especially agoraphobia. METHOD: Data were drawn from a large (n = 1,168) treatment study of panic disorder in which panic attacks were carefully subtyped and counted using a diary. Relationships between variables at baseline were examined primarily using non-parametric methods, and the course of improvement for panic subtypes among completers was plotted. RESULTS: The median number of spontaneous panic attacks per week at baseline was similar among patients with panic disorder without agoraphobia (PD), limited phobic avoidance (PDL), and agoraphobia (PDA). The median number of situational attacks and the median agoraphobia ratings rose progressively across diagnostic subtypes. Anticipatory anxiety, HAM-A, HAM-D, and disability scores were higher in PDA than in PD. Full and limited symptom panic attacks were positively correlated. The proportion of total attacks that were limited rose during the first two weeks of treatment, suggesting conversion of full to limited symptom attacks before complete disappearance. Spontaneous and situational attacks were correlated minimally or not at all. Agoraphobia ratings were more positively correlated with situational than with spontaneous panic attacks. Few of the correlations among measures at baseline were high. CONCLUSIONS: Full and limited symptom panic attacks differ primarily in severity. Spontaneous and situational attacks are relatively independent, and situational attacks are more closely related to agoraphobia. These findings are consistent with previous work suggesting that spontaneous attacks reflect a biological component, whereas situational attacks reflect a cognitive component in the psychopathology-- and possibly the pathogenesis-- of panic disorder. This provides a rationale for the use of combined pharmacotherapy and psychotherapy in the treatment of panic disorder. Future investigations of panic disorder should carefully separate panic attack subtypes.     

Long-term outcome of panic disorder with agoraphobia treated by exposure.

BACKGROUND: There is a paucity of long-term outcome studies of panic disorder that exceed a 2-year follow-up. The aim of the study was to evaluate the long-term follow-up of patients with panic disorder with agoraphobia treated according to a standardized protocol. METHODS: A consecutive series of 200 patients satisfying the DSM-IV criteria for panic disorder with agoraphobia was treated in an out-patient clinic with behavioural methods based on exposure homework. One hundred and thirty-six patients became panic free after 12 sessions of psychotherapy and 132 were available for follow-up. A 2- to 14-year (median = 8 years) follow-up was performed. Survival analysis was employed to characterize the clinical course of patients. RESULTS: Thirty-one of the 132 patients (23%) had a relapse of panic disorder at some time during follow-up. The estimated cumulative percentage of patients remaining in remission was 93.1 after 2 years, 82.4 after 5 years, 78.8 after 7 years and 62.1 after 10 years. Such probabilities increased with younger age, and in the absence of a personality disorder, of high pre-treatment levels of depressed mood, of residual agoraphobic avoidance after exposure, and of concurrent use of benzodiazepines and antidepressant drugs. CONCLUSIONS: The findings suggest that exposure treatment can provide lasting relief to the majority of patients with panic disorder and agoraphobia. Disappearance of residual and subclinical agoraphobic avoidance, and not simply of panic attacks, should be the aim of exposure therapy.     

Nonfearful panic disorder in chest pain patients

The prevalence of non-fearful panic disorder (panic attacks without the experience of fear) was estimated in 199 patients consecutively referred to outpatient cardiac investigation for chest pain. Fifty-nine patients met the criteria for panic disorder, and 17 patients fulfilled the criteria for non-fearful panic disorder. The patients with non-fearful panic disorder had lower scores on self-reported panic symptoms and lower frequencies of agoraphobia and comorbid axis I disorders than the patients with panic disorder and had a higher prevalence of somatic disorders than the patients without panic disorder. The patients with non-fearful panic disorder did not differ significantly from the patients with panic disorder in health-related quality of life.     

Major depression in patients with panic disorder: factors associated with course and recurrence

The relationship between anxiety and depressive disorders has been the subject of considerable interest and controversy. In this study, the occurrence and course of affective illness was systematically examined in 63 patients meeting DSM-III-R criteria for panic disorder. Forty (63%) of the patients had experienced at least one major depressive episode. Of these, 13 (32.5%) experienced their first depressive episode prior to the onset of panic disorder, 15 (37.5%) experienced their first depressive episode after the onset of panic disorder, and in 12 (30.0%) the onset of the disorders was concurrent. Patients with agoraphobia had comparable rates of depression (68%) to patients without agoraphobia (53%, P = NS), and they had similar temporal patterns of depressive illness. Comorbidity with social phobia was associated with an increased longitudinal likelihood of major depression compared to patients without this comorbid diagnosis (P less than 0.05). Patients with longer duration of illness, early onset depression, melancholic depression, or family histories of anxiety or depression had an increased likelihood of having experienced recurrent depression. These findings are discussed in the context of current theories regarding the development of affective illness in patients with anxiety disorders.     

Clinical subtypes in panic disorder: their descriptive and prospective validity

In a sample of 97 patients with panic attacks, presence of agoraphobia was associated with a more severe syndrome of panic anxiety both at index assessment and during one-year follow-up but was not associated with increased incidence of major depression. Groups with a history of depression--primary or secondary to the onset of panic--did not differ from the group without depression when severity of anxiety was concerned but were more severely impaired and had a higher incidence of further depressive episodes during follow-up. For future classification of panic disorder, subtypes defined according to associated syndromes of agoraphobia or depression are proposed, since these conditions appear constant through follow-up.     

The relationship between agoraphobia symptoms and panic disorder in a non-clinical sample of adolescents

BACKGROUND: The purpose of this study was to evaluate the clinical correlates of agoraphobic fear and avoidance and panic disorder in a non-clinical sample of adolescents. METHOD: In a sample of 2365 high school students, combined data from a questionnaire and a structured clinical interview were used to classify subjects with agoraphobic fear and avoidance. Panic symptoms, major depression, childhood separation anxiety disorder, anxiety sensitivity and negative affectivity were also assessed. RESULTS: Fifteen subjects met study criteria for agoraphobic fear and avoidance in the past year. Only three (20%) of those with agoraphobia symptoms reported histories of panic attacks and there was no overlap between those with agoraphobic fear and avoidance and the 12 subjects who met DSM-III-R criteria for panic disorder. However, subjects with agoraphobia symptoms and those with panic disorder reported similar levels of anxiety sensitivity and negative affectivity. Childhood separation anxiety disorder was more common among those with agoraphobic fear and avoidance compared to those without. CONCLUSION: Agoraphobic avoidance is rare in non-clinical samples of adolescents and usually not associated with panic attacks. However, adolescents with agoraphobia symptoms and those with panic disorder have similar clinical correlates consistent with a panic/agoraphobia spectrum model.     

Characterological traits of recovered patients with panic disorder and agoraphobia.

Three self-rating personality inventories were administered to 33 patients who had recovered from panic disorder associated with agoraphobia and to 33 healthy subjects matched for sociodemographic variables. The personality inventories comprised the Tridimensional Personality Questionnaire (TPQ), which provides three major dimensions (novelty seeking, harm avoidance and reward dependence), the Anxiety Sensitivity Index (ASI) and the Emotional Inhibition Scale (EIS). Agoraphobic patients reported significantly more TPQ harm avoidance and anxiety sensitivity than controls. Although these findings might have been influenced by residual anxiety symptoms in panic-free patients and could also apply to patients with other anxiety disorders, they suggest that harm avoidance and anxiety sensitivity may be risk factors for developing agoraphobia and panic disorder. There may be overlap between this characterologic cluster and prodromal symptoms of panic disorder with agoraphobia, such as anxiety, phobias and hypochondriasis.     

Quality of life in early phases of panic disorder: predictive factors

OBJECTIVE: To analyse the quality of life (QoL) of patients with panic disorder of recent onset and to find related clinical variables. METHOD: Panic disorder patients with and without agoraphobia (N=125) in the first stages of the disorder (median of 8 months since the first panic attack) were compared with a community control group. Quality of life was evaluated by 36-item Short-Form Health Survey (SF-36) and by a single-item scale evaluating subjective well-being. RESULTS: Panic disorder patients had worse scores than the general population in all of the dimensions of the SF-36. Anxiety and depressive symptoms, age, frequency of panic attacks and agoraphobic avoidance accounted for 18-42% of the variance in QoL scores. Frequency of panic attacks and agoraphobic avoidance were variables accounting for poor QoL in physical functioning and mental health respectively. However, unspecific factors in addition to panic symptomatology, particularly depressive and anxiety symptoms, significantly contribute to the worse QoL of these patients. CONCLUSION: Panic disorder of recent onset is a deteriorating condition. Clinical variables do not equally affect mental health and physical functioning, and unspecific factors in addition to panic contribute to the poor QoL.     

A comparison of patients with illness phobia and panic disorder.

Fourteen subjects with illness phobia, a subtype of hypochondriasis, were compared with an equal number of subjects with panic disorder who had been matched for age and sex. The illness phobic subjects differed from panic subjects in not having spontaneous panic attacks or agoraphobic symptoms, the characteristic features of panic disorder. The onset of illness phobia was related to experience with illness in half the subjects. Half of the illness phobic subjects also had family histories of anxiety disorders. The results suggest that illness phobia is distinct from panic disorder and that it is a disorder in which environmental and genetic factors are etiologically important.     

Psychological well-being and residual symptoms in remitted patients with panic disorder and agoraphobia

BACKGROUND: Little is known about psychological well-being in remitted patients with panic disorder and agoraphobia and its interactions with residual symptoms. METHODS: Thirty patients with panic disorder and agoraphobia who displayed a successful response to exposure therapy, and 30 control subject matched for sociodemographic variables, were administered both observer-rated and self-rated scales for assessing residual symptoms and well-being. RESULTS: Patients had significantly more residual symptoms -- as assessed by the Clinical Interview for Depression (CID) and the Symptom Questionnaire (SQ) -- than controls. They also had significantly less environmental mastery, personal growth, purpose in life and self-acceptance -- as measured by the Psychological Well-being Scales (PWB) -- and less SQ physical well-being than controls. LIMITATION: The findings apply to patients with panic disorders who had been treated by behavioral methods and may be different in drug-treated subjects. CONCLUSIONS: The results indicate that successful reduction of symptomatology in panic disorder cannot be equated to a pervasive recovery (encompassing psychological well-being) and may pave the way for sequential therapeutic strategies of more enduring quality.     

Mechanisms of change of panic attacks with exposure treatment of agoraphobia.

In vivo exposure homework was applied to a consecutive series of 30 outpatients suffering from DSM-IIIR panic disorder with agoraphobia. Assessment of the characteristics of panic attacks (the prodromal phase immediately preceding the attack, acute peak anxiety, and the residual phase immediately afterwards) was done by an independent rater before treatment, after six sessions and at the end of therapy (12 sessions). Twenty-five of the 30 patients completed treatment. All of them still reported panic attacks after six sessions, even though the characteristics of panic partially improved. At the end of therapy, panic attacks disappeared in 21 of the 25 patients (84%) and these gains were maintained to 1 year follow-up thereafter by the majority (81%) of subjects.     

Sleep quality in patients with panic disorder: Relationship to nocturnal panic attacks

Summary Question of the Study Insomnia complaints are common in patients with panic disorder. Polysomnographic studies have confirmed patients' poorer sleep quality. The present study investigates subjective sleep quality and its relationship to nocturnal panic attacks.
Patients and Methods Fifty-four outpatients with panic disorder were included. During the course of diagnostic and therapeutic procedures, the patients completed several questionnaires assessing sleep quality, nocturnal panic attacks and panic symptomatology.
Results As expected, sleep quality was markedly reduced in the sample. In addition to ­insomnia complaints, restless legs symptoms and parasomnias were reported more often. Patients with nocturnal panic attacks reported lower sleep quality than the other patients, a finding that was not influenced by course or duration of the panic disorder.
Conclusions We suggest that assessment and specialized treatment of comorbid sleep disorders is very helpful for this patient group, especially for patients who suffer from nocturnal panic attacks.     

Blood-injury related phobic avoidance as predictor of nonresponse to pharmacotherapy in panic disorder with agoraphobia

BACKGROUND: Several factors have been investigated as possible predictors of nonresponse to pharmacotherapy in Panic Disorder (PD) patients. In 1995 a study was published by Slaap et al. in this journal that found high Blood-Injury phobia scores on the Marks and Matthews Fear Questionnaire were predictive for a worse treatment-outcome for drug treatment in PD. METHODS: The present paper describes a replication study with 61 PD patients, by means of a retrospective chart analysis, who were assessed at baseline and after 12 weeks of SSRI-treatment. Nonresponse was defined as still having panic attacks. Response was defined as absence of panic attacks and/or a reduction of at least 50% on the FQ Agoraphobia subscale. RESULTS: Twenty (32%) patients were nonresponders. Nonresponders had a higher score on the FQ Blood-Injury subscale more often (55%) than responders (19.5%), significant at P=0.008. These results fully support the findings of Slaap et al. Implications of these findings are further discussed. LIMITATIONS: Limitations of this study are the retrospective design, and the absence of other psycho-physiological parameters of the specific blood-injury phobic complex. CONCLUSIONS: However, it is tentatively concluded that the presence of comorbid blood-injury related phobic symptoms negatively affects treatment for panic disorder and agoraphobia.     

Validity study of the Anxiety Symptoms Interview

The Anxiety Symptoms Interview (ASI) is a diagnostic instrument designed to identify agoraphobia (with and without panic attacks), panic disorder, social phobia, and obsessive compulsive disorder according to DSM-III criteria. The present study evaluated the diagnostic validity of this instrument by examining the extent to which ASI diagnoses assigned to 73 clinic patients agreed with diagnoses determined by clinicians. Most kappa coefficients and other concordance indicators were in the acceptable range or above, a finding that held for diagnoses overall and for specific diagnoses of agoraphobia with panic attacks, social phobia, and obsessive compulsive disorder. However, none of the 73 patients had clinician-assigned diagnoses of panic disorder (that is, without agoraphobia) or agoraphobia without panic. Limitations and applications of the ASI are discussed.     

Differential clinical features of late-onset panic disorder

OBJECTIVES: The aim was to analyse the sociodemographic and clinical characteristics of panic disorder (PD) in patients with a PD onset after 60 years of age, at two outpatient psychiatric clinics in Barcelona (northeastern Spain). MATERIAL AND METHODS: All patients presenting with PD at two outpatient clinics over a 4-year period were assessed by the same team. Patients with PD onset at 60 or after were grouped (late-onset), and compared with the group with an earlier onset. The instruments administered to the sample were: Global Assessment of Functioning scale, Panic-Associated Symptom Scale, Hamilton's Depression and Anxiety Scales and Marks-Matthews' Fear and Phobia scale. RESULTS: Of 5301 patients attended over a 4-year period, 64 (1.2%) were PD patients aged 60 or above. Age at PD onset was over 60 in 27 cases (0.4% of the total population, and 6.1% of all PD patients). The mean age in the late-onset group was 67.0+/-4.9 years. Late-onset PD patients were less likely to report family history of PD. They scored lower on most scales assessing clinical severity (excepting GAF and agoraphobia scores), and they exhibited fewer and milder panic symptoms during the attacks. However, dysthymic disorder, but not major depressive disorder, was more common among late-onset PD patients (P<0.05). COMMENTS: The most notable findings in our late-onset PD subgroup of patients were: lesser severity of the disorder, greater comorbidity with dysthymia, and less family history of PD. Prevalence rates of late-onset PD in our sample appeared to be rather high. Physical illness and less severe panic symptoms may contribute to underdiagnosing PD in this particular subpopulation.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

Antidepressants in panic disorder and agoraphobia

A survey of the literature on the use of antidepressants for treating patients with panic disorder and agoraphobia with panic attacks suggests that both tricyclic antidepressants and monoamine oxidase inhibitors have efficacy in blocking panic attacks. While we have witnessed dramatic progress in the pharmacological treatment of panic-related disorders over the past 20 years, many unresolved questions remain. Further understanding of dose-response relationships, optimal duration of treatment and predictors of relapse are needed to optimize pharmacological treatment of panic-related disorders. Studies comparing the relative efficacy and side effects spectrum of various effective medications are needed. It is not presently possible to specify which patients will require medication or behavioral treatment alone, and studies to date have incompletely examined this murky issue. Further prospective studies directly comparing the pharmacological and behavioral treatments will help further elucidate the relative contribution of each treatment and possibly clarify which patients require both treatments. Controlled studies in the future which standardize dosage and duration of treatment and use comparable, objective outcome variables promise to provide important theoretical and clinical information regarding the pharmacological treatment of panic-related disorders.     

Specificity of lactate response in panic disorder, panic with concurrent depression and major depression

Lactate infusions with 0.5 molar sodium lactate in a dose of 10 ml/kg within 20 min were given to patients with panic disorder (n = 6), panic attacks with concurrent major depression (n = 7) and major depression without panic (n = 5). Lactate-induced anxiety and symptom attacks without panic were seen more often in the groups with panic attacks, but a full-blown panic attack was provoked in only four subjects, all belonging to the groups with a history of panic attacks. The low incidence of lactate-induced panic attacks can be explained by differences in the procedure that aimed at reducing expectancy biases and baseline anxiety.     

Comparison of panic disordered patients with high versus low MHPG

Fourteen panic disorder patients with low 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared to 14 patients with high MHPG. Patients with low MHPG were more likely during the preceding month to have experienced spontaneous panic attacks (P less than 0.008) than were patients with high MHPG. Patients with high MHPG had increased severity ratings on several individual symptoms of anxiety.