Outcome of panic disorder. Relationship to diagnostic subtypes and comorbidity

Eighty-nine subjects with panic disorder, who had been naturalistically treated, and 46 nonanxious controls were followed up after 3 years. Although they remained symptomatic, most subjects with panic disorder reported relatively little distress or social maladjustment. The course of panic disorder was characterized by fluctuating anxiety and depressive symptoms. Panic subtypes (uncomplicated, limited phobic avoidance, and extensive phobic avoidance) and Axis I and II comorbidity (major depression and personality disorders) were highly predictive of symptoms and social adjustment after 3 years. Abnormal personality was, in fact, the strongest predictor of social maladjustment in both subjects with panic disorder and controls. The results showed that while panic disorder has a favorable outcome, the illness is a chronic one that may require continuing treatment. They also show that subtypes and comorbid disturbances are important predictors of outcome.     

Predictors of serious suicide attempts among patients with panic disorder

Of 74 panic disorder subjects followed up after 7 years, five reported serious suicide attempts and three had completed suicide. Compared with subjects who had not made serious attempts, the serious suicide attempters (including the three suicides) were younger, and fewer of them were married. Also, the serious attempt group had an earlier, more gradual onset of illness. More of the serious attempters had personality disorders and coexisting major depression. At the time of original assessment, the serious attempters had more severe symptoms. These data suggest that among patients with panic disorder, serious suicidal behavior is associated with more severe psychopathology.     

Personality differences in the Munich Personality Test between patients with major depression and panic disorder

This study attempted to determine whether patients with major depression and panic disorder could be differentiated by personality features, measured by the Munich Personality Test (MPT). One of the six MPT personality dimensions, `rigidity', was developed in relation to the `melancholic type of personality', which may be a specific personality feature of depressive subjects. We therefore hypothesized that the MPT might be sensitive to possible personality differences between patients with major depression and panic disorder. Sixty-six patients with major depression and 27 patients with panic disorder, taken from consecutive intakes at an outpatient unit, were compared in terms of six personality dimensions of the MPT. The results demonstrated that rigidity could significantly differentiate the two patient groups, even after the possible confounding effects on the personality assessments were statistically partialled out. The MPT was suggested to be powerful for describing distinctive personality features of depressive subjects from anxiety subjects.     

Comorbid personality disorders in subjects with panic disorder: do personality disorders increase clinical severity?

Personality disorders are common in subjects with panic disorder. Personality disorders have been shown to affect the course of panic disorder. The purpose of this study was to examine which personality disorders affect clinical severity in subjects with panic disorder. This study included 122 adults (71 women, 41 men) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM-IV ) criteria for panic disorder (with or without agoraphobia). Clinical assessment was conducted by using the Structured Clinical Interview for DSM-IV Axis I Disorders, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Panic and Agoraphobia Scale, Global Assessment Functioning Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory. Patients who had a history of sexual abuse were assessed with Sexual Abuse Severity Scale. Logistic regressions were used to identify predictors of suicide attempts, suicidal ideation, sexual abuse, and early onset of disorder. The rates of comorbid Axes I and II psychiatric disorders were 80.3% and 33.9%, respectively, in patients with panic disorder. Patients with panic disorder with comorbid personality disorders had more severe anxiety, depression, and agoraphobia symptoms, had earlier ages at onset, and had lower levels of functioning. The rates of suicidal ideation and suicide attempts were 34.8% and 9.8%, respectively, in subjects with panic disorder. The rate of patients with panic disorder and a history of childhood sexual abuse was 12.5%. The predictor of sexual abuse was borderline personality disorder. The predictors of suicide attempt were comorbid paranoid and borderline personality disorders, and the predictors of suicidal ideation were comorbid major depression and avoidant personality disorder in subjects with panic disorder. In conclusion, this study documents that comorbid personality disorders increase the clinical severity of panic disorder. Borderline personality disorder may be the predictor of a history of sexual abuse and early onset in patients with panic disorder. Paranoid and borderline personality disorders may be associated with a high frequency of suicide attempts in patients with panic disorder.     

Specificity of panic response to CO(2) inhalation in panic disorder: a comparison with major depression and premenstrual dysphoric disorder

OBJECTIVE: The behavioral response to CO(2) inhalation has been used to differentiate panic disorder patients from normal subjects and other clinical populations. This study extended examination of the diagnostic specificity of CO(2)-induced anxiety by testing panic disorder patients and clinical populations with reported low and high sensitivity to CO(2) inhalation (patients with major depression and patients with premenstrual dysphoric disorder, respectively). METHOD: The behavioral responses to inhalation of 5% and 7% CO(2), administered by means of a respiratory canopy, were studied in 50 patients with panic disorder, 21 with major depression, and 10 with premenstrual dysphoric disorder and in 34 normal comparison subjects. Occurrence of panic attacks was judged with DSM-IV criteria by a blind rater. Subjects were rated on three behavioral scales at baseline and after each CO(2) inhalation. RESULTS: Panic disorder patients had a higher rate of CO(2)-induced panic attacks than depressed patients and normal subjects, whose panic rates were not distinguishable. The panic rate for patients with premenstrual dysphoric disorder was similar to that for panic disorder patients and higher than that for normal subjects. Subjects with CO(2)-induced panic attacks had similarly high ratings on the behavioral scales, regardless of diagnosis, including the small number of panicking normal subjects. Seven percent CO(2) was a more robust panicogen than 5%, and response to 7% CO(2 )better distinguished panic disorder patients from normal subjects than response to 5% CO(2). CONCLUSIONS: Patients with panic disorder and patients with premenstrual dysphoric disorder are highly susceptible to CO(2)-induced panic attacks, and depressed patients appear to be insensitive to CO(2) inhalation. The symptoms of CO(2)-induced panic attacks have a similar intensity regardless of the subject's diagnosis.     

Electroconvulsive therapy in a physically restrained man with comorbid major depression, severe agoraphobia with panic disorder, and histrionic personality disorder

A 36-year-old man with comorbid panic disorder with agoraphobia, major depression, and histrionic personality disorder since age 21 was resistant to combined drug and psychotherapy treatment. His conditions had progressively worsened with time, causing him to withdraw socially and to simultaneously require continuous physical restraint, which further worsened his functioning. He spent almost 3 consecutive years in restraint, until he consented to receive bilateral ECT treatment. He improved after 13 sessions in all areas (social and role functioning, and panic, depressive, and histrionic symptoms) and is well 3 months later with a lithium-atypical antipsychotic combination.     

Dependent personality disorder associated with phobic avoidance in patients with panic disorder

Eighty-eight panic disorder patients were divided into three groups according to the extent of their phobic avoidance (none, limited, or extensive). These groups were compared on three personality disorder instruments: the Structured Interview for DSM-III Personality Disorders, the Personality Diagnostic Questionnaire, and the Millon Clinical Multiaxial Inventory. Phobic patients were found to have significantly more dependent personality disorder and DSM-III third-cluster personality disorders than nonphobic patients. A subgroup of patients with social phobic symptoms was found to resemble the rest of the phobic group in terms of personality.     

Vasopressin response to lactate infusion in normals and patients with panic disorder

Infusions of sodium lactate evoke panic symptoms in patients with panic disorder but not in normal subjects. Although plasma vasopressin (AVP) is known to rise in response to other forms of stress, its response during this maneuver has not previously been reported. We measured plasma AVP in double-blind infusions of sodium lactate in 5 normal subjects, 6 patients with panic disorder, and, again in 4 patients after chronic alprazolam. In all groups administered lactate, AVP rose significantly above baseline values (p less than 0.05) though no change was seen in a control group of patients during D5NS infusion. No difference in AVP response to lactate was apparent between untreated patients (who experienced panic) and normals or chronically treated patients (who had minimal symptoms). Thus, the presence of panic symptoms induced by lactate is insufficient to provoke an abnormal pattern of AVP release.     

DSM-II personality characteristics of panic disorder with agoraphobia patients in stable remission.

The Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess DSM-III axis II personality disorders (PD), was administered to 12 panic disorder with agoraphobia patients during a 6-month stable and virtually symptom-free remission period with the aim of assessing the personality characteristics of these patients in the best possible approximation of the not-ill condition in clinical reality. The personality profile of the sample remained unchanged during remission and was predominated by avoidant PD traits. In a finer grain analysis, the stable and commonly endorsed individual PDQ items were compared with previously reported panic disorder and normal control subjects, which showed that the present sample was more like the panic patients in their tendency to see themselves as rather unassertive, indecisive, self-critical, and emotional individuals who are easily frustrated and feel rejected when criticized by others. These results suggest that avoidant behavioral and attitudinal patterns may be enduring personality characteristics of panic disorder with agoraphobia patients.     

The acute antipanic and anxiolytic activity of aerobic exercise in patients with panic disorder and healthy control subjects

Regular physical activity is anxiolytic in both healthy subjects and patients with panic disorder. In contrast, acute exercise may induce acute panic attacks or increase subjective anxiety in patients with panic disorder more than in other people. The effects of quiet rest or an aerobic treadmill exercise (30 min at an intensity of 70% of the maximal oxygen uptake, VO_2max) on cholecystokinin tetrapeptide (CCK-4) induced panic attacks were studied in a crossover design in 12 patients with panic disorder and 12 matched healthy subjects. The effects of CCK-4 (25 μg in patients and 50 μg in control subjects) were measured with the Acute Panic Inventory (API) score, comparing panic attack frequencies, total score, and subscores for anxiety and somatic symptoms. CCK-4-induced panic attacks were less frequent after prior exercise: they occurred in 15 (62.5%) subjects after rest (9 patients and 6 control subjects), but only 5 (20.8%) subjects after exercise (4 patients and 1 control subject). In both conditions, CCK-4 administration induced a significant increase in the total API score and the anxiety and somatic symptoms subsores. However, compared to prior rest, exercise resulted in a significantly reduced CCK-4-induced increase of the total API score and the anxiety subscore. In patients with panic disorder exercise increased the total API score and the somatic symptoms subscale but not the anxiety subscore. Patients with panic disorder showed increased somatic but not anxiety symptoms after an acute bout of exercise. Severity of CCK-4-induced panic and anxiety, on the other hand was reduced by exercise. These findings suggest that in addition to exercise training an acute bout of exercise may be used to reduce anxiety and panic attack frequency and intensity in panic disorder patients.     

Suicidal ideation and suicide attempts among patients with panic disorder: a survey of two outpatient clinics.

OBJECTIVE: Recent epidemiologic studies found that 20% of subjects with the diagnosis of panic disorder had attempted suicide. This study sought to determine the prevalence of suicidal ideation and suicide attempts among patients with panic disorder and whether the presence of comorbid borderline personality disorder influenced the prevalence of suicidal thoughts and behavior. METHOD: At two outpatient clinics, experienced clinicians conducted retrospective reviews of data from the intake interviews and charts of 59 patients with panic disorder and comorbid borderline personality disorder and 234 patients with panic disorder with or without axis II disorders other than borderline personality disorder. RESULTS: Suicide attempts were reported by 2% of the patients with panic disorder, compared to 25% of the patients with both panic disorder and borderline personality disorder. In addition, 2% of the patients with panic disorder, compared to 27% of the patients with panic disorder and borderline personality disorder, reported suicidal ideation that was judged to be of clinical significance. CONCLUSIONS: The rate of suicidal ideation and suicide attempts for psychiatric outpatients with panic disorder was discrepant with the findings of the earlier studies. The increased suicide risk in this group of patients was associated with borderline personality disorder, increased substance abuse, and affective instability. While 61% of the panic disorder patients and 78% of the patients with both panic disorder and borderline personality disorder reported thinking about death, this must be distinguished from actual suicidal ideation and clinical risk of suicide.     

Panic disorder versus panic disorder with major depression: Defining and understanding differences in psychiatric morbidity

The present study examined the impact of comorbid major depressive disorder (MDD) on psychiatric morbidity, panic symptomatology and frequency of other comorbid psychiatric conditions in subjects with panic disorder (PD). Four hundred thirty-seven patients with PD were evaluated at intake as part of a multicenter longitudinal study of anxiety disorders; 113 of these patients were also in an episode of MDD. Patients were diagnosed by DSM-III-R criteria utilizing structured clinical interviews. The 113 PD/MDD patients were compared with the 324 remaining PD subjects regarding panic symptoms at intake, sociodemographic, quality of life and psychiatric morbidity variables. Differences in frequency of other comorbid Axis I psychiatric disorders were assessed at intake; personality disorders were evaluated twelve months after intake. The results revealed that PD/MDD patients exhibit increased morbidity and decreased psychosocial functioning as compared to PD patients. Personality disorders were more prevalent in the PD/MDD group at six month follow-up assessment; the PD/MDD group also had an increased frequency of posttraumatic stress disorder (PTSD) and more comorbid Axis I anxiety disorders as compared to the PD group. The total number and frequency of panic symptoms was highly consistent between the two patient groups. Depression and Anxiety 5:12–20, 1997. © 1997 Wiley-Liss, Inc.     

High cholesterol levels in patients with panic disorder.

OBJECTIVE: This study was undertaken to help clarify whether the higher cholesterol levels found in patients with panic disorder are a complication of panic disorder only or are associated with any psychiatric disorder. METHOD: The subjects of the study were 30 patients with panic disorder and 30 patients with major depression, diagnosed according to the Structured Interview for DSM-III-R, and 30 normal control subjects. The three groups were matched for sex and age, and none of the subjects had alcohol/drug abuse, abnormal ECGs, or unstable medical conditions. Blood samples were drawn at random times, and serum cholesterol levels were determined. RESULTS: The patients with panic disorder had significantly higher serum cholesterol levels than did the patients with major depression and the normal control subjects. Among the patients with major depression, histories (current or past) of anxiety disorders were associated with significant elevation of serum cholesterol levels. The presence of stable medical conditions was not associated with higher cholesterol levels in any of the three groups of subjects. CONCLUSIONS: Higher cholesterol levels were particularly associated with panic disorder in comparison with major depression. Higher levels of cholesterol in panic disorder are hypothesized to be a result of increased noradrenergic activity, which may be the underlying biological/neurochemical mechanism for symptoms of panic disorder, including anticipatory anxiety.     

A cerebrospinal fluid study of the pathophysiology of panic disorder associated with alcoholism.

In order to investigate the neurochemistry of panic disorder in alcoholics, we measured various cerebrospinal fluid (CSF) parameters in subjects with both conditions and compared them with an age- and sex-matched population of alcoholics and normal controls. When height, age and weight were covaried, subjects with panic disorder had higher levels of B-endorphin in CSF. There were no differences in other CSF measures between the groups. Alcoholics with panic disorder had higher plasma MHPG concentrations compared with alcoholics without panic disorder but these were not statistically different from controls.     

Personality disorders in patients with panic disorder: association with childhood anxiety disorders, early trauma, comorbidity, and chronicity.

The rates of comorbid personality disorders in patients with panic disorder are reported to be elevated, have an adverse impact on the response to treatment, and increase the likelihood of relapse on treatment discontinuation. We examined the rates of personality disorders in panic disorder patients in a longitudinal, naturalistic study of panic disorder. Of 100 panic disorder patients studied, 42 met criteria for at least one personality disorder as determined by the Personality Disorder Questionnaire-Revised (PDQ-R). The presence of a personality disorder as determined by the PDQ-R was associated with a past history of childhood anxiety disorders, comorbidity with other anxiety disorders and depression, and a chronic, unremitting course of panic disorder in adulthood. The presence of a personality disorder in these patients was not significantly associated with a history of physical or sexual abuse in childhood. Our findings support the notion that an anxiety diathesis, demonstrated by significant difficulties with anxiety in childhood, influences the development of apparent personality dysfunction in panic patients. In other cases, personality pathology may reflect the presence of comorbid anxiety disorders or depression. The association of personality disorder in panic patients with a more unremitting course of illness underscores the importance of axis II pathology in understanding the longitudinal course of panic disorder.     

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.     

Sensitivity to carbon dioxide in subjects with a single lifetime panic attack: possible clinical "bedside" predictive test for panic disorder after a first attack

There is currently no way of knowing whether a patient who has recently had a single panic attack has incipient panic disorder. Sensitivity to carbon dioxide (CO2) is lower in healthy volunteers than in panic disorder patients. If this is also true of people who experience a single lifetime panic attack, it could be used as a prognostic test. Subjects with a single lifetime panic attack and subjects with panic disorder received an inhalation of 35% CO2. Subjects completed the panic symptoms scale (PSS), and also stated whether they considered that they had experienced an attack. None of 14 subjects with a single lifetime panic attack, compared to 7 of 17 subjects with panic disorder (P=.009), had an attack. The PSS also distinguished between the groups. The 35% CO2 challenge warrants further investigation as a predictive test after a first panic attack.     

Panic induced by carbon dioxide inhalation and lack of hypothalamic-pituitary-adrenal axis activation.

It has been hypothesized that spontaneous panic is distinct from anticipatory anxiety, which activates the hypothalamic-pituitary-adrenal (HPA) axis. Panic attacks characterized by prominent respiratory symptoms, such as those induced by sodium lactate, are not associated with increases in cortisol. We examined blood cortisol responses to CO2-induced panic. Cortisol levels did not increase and actually decreased significantly in 10 panicking subjects with panic disorder. No reductions were noted after 20 min of CO2 inhalation in either eight normal comparison subjects or six non-panicking panic disorder patients. These results lend support to the hypothesis that the pathophysiological mechanism underlying CO2-induced panic is different from that underlying general or anticipatory anxiety.     

The effects of comorbid personality disorders on cognitive behavioral treatment for panic disorder

The present study investigated the influence of personality pathology assessed both dimensionally and categorically on acute clinical response to group cognitive-behavioral treatment in a large sample of panic disorder patients (N = 173) meeting DSMIII-R criteria for panic disorder with or without agoraphobia. Nearly one-third of the sample met for one or more personality disorders, with the majority meeting for a Cluster C diagnosis. Patients with one or more comorbid personality disorders displayed higher baseline and higher post treatment scores across multiple indices of panic disorder severity compared to those without personality disorders. After controlling for panic disorder severity at baseline, the presence of both Cluster C and Cluster A Pers-Ds predicted a poorer outcome, whereas when assessed dimensionally, only Cluster C symptoms predicted a poorer treatment response. However, the influence of personality pathology was modest relative to that of baseline panic disorder severity.     

Remission and relapse in subjects with panic disorder and panic with agoraphobia: a prospective short-interval naturalistic follow-up

This article reports on the course of uncomplicated panic disorder and panic with agoraphobia on 309 patients participating in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of patients with DSM-III-R-defined anxiety disorders. At 1 year, there was a .39 probability of full remission for uncomplicated panic disorder and a .17 probability of full remission for panic disorder with agoraphobia Similar differences in time to remission for these syndromes were still found when criteria for remission were made less stringent. However, even requiring less improvement for remission left a large percentage of subjects in an episode, and for those that remitted, relapse occurred quickly, indicating a chronic and recurrent course of illness. This is the first longitudinal, prospective, naturalistic study on a large cohort of subjects with anxiety disorders to have regular, structured, short-interval follow-up. Our results are consistent with the view that panic disorder has a chronic course with high rates of relapse after remission and longer episodes when agoraphobia is a part of the constellation of symptoms.