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.     

Sex differences in panic disorder with agoraphobia

Two hundred seventy-two patients (68 males and 204 females) with DSM-III diagnosis of Agoraphobia with Panic Attacks (300.21) were used in the present study to investigate sex differences in these patients. Discriminant analysis showed that female agoraphobics can be significantly differentiated from male agoraphobics on their responses to the Fear Survey Schedule (FSS), the clinicians ratings on the Hamilton Anxiety Scale (HAM-H), and Hamilton Depression Scale (HAM-D), indicating the expression of more severe symptomatology amongst the female agoraphobics. Female and male agoraphobics could not, however, be differentiated using the Fear Questionnaire (FQ), Hostility and Direction of Hostility Questionnaire (HDHQ), Maudsley Personality Inventory (MPI), and the State-Trait Anxiety Inventory (STAI), panic symptoms, and cognitions associated with panic attacks. The paper concluded that there were no real differences between the male and female agoraphobics with panic attacks.     

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.     

Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks

Patients who met DSM-III criteria for agoraphobia with panic attacks underwent dexamethasone suppression tests (DSTs) before, during, and after treatment with alprazolam or placebo. Similarly, outpatients with major depression were given multiple DSTs as they participated in a study of desmethylimipramine efficacy. The likelihood of an abnormal escape from dexamethasone was similar in the two diagnostic groups; nonsuppression was somewhat more likely among patients with primary depression, but comparisons with agoraphobic groups remained statistically insignificant. These results apparently did not reflect misclassification of primary depression patients as agoraphobics since a history of major depression was not related to the likelihood of nonsuppression within that group. Moreover, change in DST results during treatment reflected clinical change among agoraphobics. After a review of relevant followup and family studies, we conclude that panic disorder and primary depression are separate illnesses and that hypothalamic-pituitary-adrenal axis hyperactivity is an epiphenomenon of both.     

Response to sodium lactate infusion in alcoholics with panic attacks

The authors studied the response to sodium lactate infusion of 12 alcoholics with a history of panic attacks, 10 alcoholics without a history of panic attacks, and 16 nonalcoholic patients with panic disorder. The rate of lactate-induced panic was significantly higher in alcoholics with panic attacks than in alcoholics without panic attacks. Alcoholics with panic attacks were similar to nonalcoholic patients with panic disorder in their response to lactate. These findings support the specificity of lactate-induced panic for panic states and suggest that panic attacks in alcoholics resemble those in nonalcoholics. Lactate infusion may prove useful in the diagnosis of panic disorder in alcoholics.     

Relationship between panic disorder and agoraphobia. A family study

A family study of patients with agoraphobia (n = 40), panic disorder (n = 40), and nonanxious controls (n = 20) showed that the morbidity risk for panic disorder was increased among the relatives of agoraphobics (8.3%) and the relatives of patients with panic disorder (17.3%). The morbidity risk for agoraphobia was also increased among the relatives of agoraphobics (11.6%) but not the relatives of panic disorder patients (1.9%). Male relatives of agoraphobics were shown to be at higher risk for alcohol disorders (30.8%). No greater risk for primary affective disorders was found among the relatives of agoraphobic or panic disorder patients or among the relatives of probands with secondary depression compared with relatives of probands without secondary depression. Probands and relatives with agoraphobia reported an earlier onset of illness, more persistent and disabling symptoms, more frequent complications, and a less favorable outcome than probands and relatives with panic disorder. The findings suggest that agoraphobia is a more severe variant of panic disorder. They also lend support to the separation between anxiety disorders and affective disorders.     

Hyperventilation challenge test in panic disorder and depression with panic attacks.

Our aim was to determine whether panic disorder (PD) patients, major depressive patients without panic attacks (MD) and major depressive patients with panic attacks (MDP) respond similarly to hyperventilation challenge tests. We randomly selected 35 PD patients, 33 MDP patients, 27 MD patients and 30 normal volunteers with no family history of anxiety or mood disorder. The patients had not been treated with psychotropic drugs for at least 1 week. They were induced to hyperventilate (30 breaths/min) for 4 min, and anxiety was assessed before and after the test. A total of 16 (45.7%) PD patients, 12 (36.4%) MDP patients, four (11.1%) MD patients, and two (6.7%) normal volunteers had a panic attack after hyperventilating. The PD and MDP patients were significantly more responsive to hyperventilation than the MD patients and the normal volunteers. The MD patients had a significantly lower heart-rate response to the test than all the other groups. There is growing evidence that PD patients are more sensitive to the vasoconstrictive effects on basilar arterial blood flow caused by hyperventilation-induced hypocapnia than are comparison subjects. Our data suggest that there is an association between panic attacks and hyperreactivity to an acute hyperventilation challenge test.     

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.     

Lactate infusions in major depression without panic attacks

Sodium lactate infusion provokes panic attacks in panic disorder patients but not in normal controls. We have previously shown that patients who develop panic disorder during a major depressive episode are similar to panic disorder patients in their rate of panic attacks with lactate. In the present pilot study, nine patients with major depression without panic attacks underwent lactate infusions. These patients differed significantly from panic disorder patients but not from controls in their response to lactate. This argues for the specificity of lactate sensitivity for the phenomenon of panic attacks and gives further evidence for biological differences between panic and depression.     

Response to sodium lactate in panic disorder: relationship to presenting clinical variables

Sodium lactate infusion provokes more physiological and psychological symptoms of panic in patients with panic attacks than in normal controls. The relationship between response to sodium lactate infusion and presenting clinical characteristics was examined in 50 patients with panic disorder or agoraphobia with panic attacks. Lactate-induced panic was significantly related only to a patient-reported family history of panic. Rating of physical symptoms during lactate infusion, but not overall response to lactate, was significantly correlated with Symptom Checklist-90 somatization scores. In general, lactate response does not identify clinically distinct subpopulations of patients with panic disorder.     

Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients

Previous research showed that lowering the availability of serotonin to the brain by tryptophan depletion increases the vulnerability of panic disorder patients for an experimental 35% CO(2) panic challenge. The results also suggested that increased availability of serotonin inhibits the response to such a challenge. In the present study, this latter possibility is examined. The reaction of 24 panic disorder patients and 24 healthy volunteers to a 35% CO(2) panic challenge was assessed following administration of 200-mg L-5-hydroxytryptophan (the immediate precursor of serotonin) or placebo. L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.     

Brief treatment of emergency room patients with panic attacks.

OBJECTIVE: Most research on treatment for panic disorder has involved chronic forms of the illness. To determine the efficacy of early intervention, the authors examined the effects of treatment for patients with panic attacks who were seen in the emergency room, which is the first point of contact with the health delivery system for many persons with panic attacks. METHOD: The subjects were 33 patients with panic attacks seen in two emergency rooms. The presence of panic attacks was confirmed with a modified version of the Structured Clinical Interview for DSM-III-R; approximately 40% of the patients met the DSM-III-R criteria for panic disorder with agoraphobia. The patients were randomly assigned to groups receiving reassurance (N = 16) or exposure instruction (N = 17). Scores on the Fear Questionnaire agoraphobia subscale, Mobility Inventory, and Beck Depression Inventory and the frequency of panic attacks were determined at baseline, 3 months, and 6 months. RESULTS: The subjects who received exposure instruction significantly improved over the 6-month period on depression, avoidance, and panic frequency. The reassurance subjects did not improve on any measure and eventually reported more agoraphobic avoidance. CONCLUSIONS: These results suggest that early intervention with exposure instruction may reduce the long-term consequences of panic attacks. The exposure instruction was of value even though the subjects had relatively low levels of avoidance at the outset of the study.     

Prolactin and sodium lactate-induced panic

Sodium lactate infusions reliably induce panic attacks in panic disorder patients but not in normal controls, but the mechanism underlying this response is unknown. We studied the plasma prolactin response to infusion of 0.5 molar sodium lactate in 38 patients with panic disorder or agoraphobia with panic attacks, and 16 normal controls. As expected, baseline plasma prolactin was significantly higher in female subjects than in male subjects. However, the males who experienced lactate-induced panic had significantly elevated baseline prolactin levels compared to male nonpanickers and controls. Prolactin levels increased in all groups during lactate infusion, which may reflect osmotic effects, but were blunted in the late panickers compared to nonpanickers and controls. The elevated baseline prolactin for male panickers supports a relationship between prolactin and anticipatory anxiety. The blunted prolactin response for late panickers suggests a net diminution, rather than a sensitization, of prolactin response in panic anxiety.     

Frequency of panic as an outcome measure in agoraphobia research: Latent effects of exposure on panic

The frequency of panic attacks during treatment of patients with panic disorder and agoraphobia was studied with an event sampling method. Treatment comprised panic management techniques followed by exposure in vivo. Results revealed that the frequency of panic attacks varied considerably across patients. There was a group of patients that responded to treatment with a decrease in both panic attacks and avoidance. Another group of patients, however, experienced little panic in the initial phase of treatment, but during the exposure phase they evidenced an increase in the frequency of panic attacks along with a decrease in avoidance. Consequently, merely focusing on panic frequency could lead to considering some patients as treatment failures, while in fact they did respond to the treatment. Recommendations for the use of panic attack frequency as an outcome measure in the evaluation of treatment for panic disorder with agoraphobia are discussed.     

Clinical characteristics and response to sodium lactate of patients with infrequent panic attacks

Nine patients with panic attacks too infrequent to meet DSM-III criteria for panic disorder were compared to 20 panic disorder patients with respect to clinical characteristics and response to sodium lactate infusion. The two groups showed similar clinical characteristics and response to lactate. The authors conclude that patients with infrequent panic attacks are clinically and biologically similar to those with panic disorder and discuss implications for the diagnosis of panic states.     

Low MHPG and continuing treatment in panic disorder

1. The paper presents a naturalistic study of 3-Methoxy-4-hydroxyphenylglycol and treatment response in panic disorder. 2. Twenty-eight patients unmedicated for at least one month were entered in a study of MHPG in panic disorder, and given the option of continuing or not continuing treatment. 3. At baseline and on average follow-up 6.8 months later, patients continuing in treatment had significantly lower MHPG than those who did not. 4. At baseline, the two groups of patients did not differ significantly as to number of panic attacks, Zung anxiety scale, and Beck and Hamilton Depression scales. 5. Treated patients did better on all clinical measures at follow-up. 6. Low MHPG may be related to persistence in seeking treatment for panic disorder, and perhaps to treatment response.     

Long-term evaluation of paroxetine,clomipramine and placebo in panic disorder

Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies. This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder. Patients who satisfactorily completed a 12-week, double-blind, placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their randomized treatment for a further 36 weeks. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. In total, 176 patients were included in the intention-to-treat population. The number of full panic attacks decreased in all three groups during the 12-week study, and improvements continued with long-term therapy. Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks, and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks. There were no significant differences between paroxetine and clomipramine. The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group (19%) than in either the paroxetine group (7%) or the placebo group (9%). Paroxetine was significantly more effective than placebo and as effective as (but better tolerated than) clomipramine in the long-term treatment of panic disorder. Not only was efficacy maintained, but continued improvement was also seen, indicating the importance of long-term treatment in patients with panic disorder.     

Placebo response in panic disorder

Of 43 patients with panic disorder or agoraphobia with panic attacks who took placebo for 8 weeks in two double-blind studies, one in four markedly improved. Those with consistently normal dexamethasone suppression test results were significantly more likely to show a placebo response as were those with lower anxiety ratings at the outset of treatment.     

Panic attacks with and without agoraphobia: a comparison

22 patients with panic disorder (PD) were compared with 42 cases suffering from agoraphobia with panic attacks for a number of variables. The two groups did not differ for age, sex ratio, age of onset, social class, severity of nonsituational anxiety and personality profiles. On the other hand agoraphobics showed lower education and worse social adaptation. A higher prevalence of traumatic life events was also observed for agoraphobics compared with subjects suffering from PD.     

Specificity of lactate infusions in social phobia versus panic disorders

Lactate infusions produced panic attacks in one of 15 patients with social phobia, four of nine with agoraphobia, and 10 of 20 with panic disorder in a blind study. The proportion of patients with social phobia who panicked in response to lactate was significantly lower than that of patients with agoraphobia or panic disorder. These findings lend validity to the DSM-III classification of anxiety states. They also suggest that the pathophysiology of social phobia differs from that of disorders characterized by spontaneous panic attacks.