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Fourteen panic disorder patients were infused with isoproterenol both before and after treatment with tricyclic antidepressants. Thirteen patients had panic attacks before treatment, and only 2 after treatment. There was a significant decrease in anxiety as measured by a Panic Description Scale during posttreatment infusions, and patients were able to tolerate longer infusions posttreatment. Isoproterenol increased systolic blood pressure and decreased diastolic blood pressure in both untreated patients and in 10 normal controls. Tricyclic antidepressant treatment of panic disorder patients abolished isoproterenol-induced increases in systolic blood pressure, but did not affect diastolic blood pressure response. These changes are consistent with a decrease in sensitivity to beta-1 receptor stimulation after treatment with tricyclic antidepressants.

To investigate autonomic function in panic disorder patients (n = 30), we compared postural changes in heart rate and the R-R interval variance in patients and normal controls (n = 20). There was no significant difference in the immediate changes in heart rate upon standing between the groups. R-R variance was significantly decreased during resting supine condition in patients as indicated by the corrected standard deviation of the R-R intervals. The standing R-R variance was significantly lower than that of normal controls as indicated by the corrected standard deviations, the corrected mean consecutive difference and the corrected standard deviation of the mean consecutive difference of the R-R intervals, suggesting an increase in vagal withdrawal in patients, especially upon standing. If this finding is specific to panic disorder patients, it may be a useful peripheral marker for this condition.

To determine which symptoms characterized isoproterenol-induced panic attacks, we analyzed the presence of panic attacks in 54 panic disorder patients who panicked, 24 patients who did not panic, and 37 controls who did not panic during isoproterenol infusions. The increases over the baseline of the symptoms shortness of breath and fear of going crazy were highly associated with panicking patients when compared to nonpanicking patients and nonpanicking controls. The increases of the symptoms trembling and shaking, generally nervous, and fear of going crazy were highly associated with patients when compared to controls. The possibility of a cognitive theory of panic attacks is discussed.

Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder.

Changes in heart rate (HR) and blood pressure (BP) were measured serially during postural changes and isometric hand grip exercise test (IHT) in 30 patients with panic disorder and 30 normal controls. Though there were no significant differences in the delta increase of HR or systolic or diastolic BP during these tests, the resting supine and standing diastolic BP were significantly higher in panic disorder patients than in controls. The standing mean BP was also significantly higher in panic disorder patients. These findings are suggestive of an increase in adrenergic tone in panic disorder patients.

Supine and standing heart rate (HR) and blood pressure measures were compared among 19 nonsmoking normal controls, 29 smoking patients and 36 nonsmoking patients with panic disorder. The smoking patients had a significantly higher supine HR, standing diastolic blood pressure, standing mean blood pressure and supine and standing cardiac load measures compared to both patient nonsmokers and controls. There was no significant difference between controls and nonsmoking patients for any of the above measures except for the higher standing HR and the delta increase in HR upon standing in female panic disorder patients which suggests increased adrenergic activity. When lipid values of panic disorder patients (n = 92) were compared to National Reference Values for their sex and age for an increased risk of cardiovascular illness, there was no significant risk with regard to plasma levels of total cholesterol, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol.

The jitteriness syndrome (jitteriness, shakiness, increased anxiety, and insomnia) can develop with low doses of tricyclic antidepressants in patients who are sensitive to these drugs. The authors review the antidepressant treatment of 180 patients. Only those with panic attacks had jitteriness, usually during the first week of treatment. Desipramine was associated with a much higher frequency of jitteriness than was imipramine. Tolerance to jitteriness occurred with continued treatment, but fewer patients with jitteriness responded to treatment, apparently because of difficulties in increasing the dose. Characteristics of the jitteriness syndrome in panic disorder patients are consistent with noradrenergic hypotheses of panic anxiety. The clinical and theoretical implications of these findings are discussed.

In a double-blind study using sodium lactate and isoproterenol infusions to provoke panic attacks, 73 of 86 panic disorder patients and 10 of 45 controls panicked with lactate, and 58 of 86 patients and 4 of 45 controls panicked with isoproterenol. We measured baseline and peak anxiety ratings in 10 controls with lactate-induced panic attacks, 31 controls who did not panic during lactate infusions, and 63 panic disorder patients who did panic during lactate infusions. The controls who panicked with lactate had robust increases in their anxiety ratings very similar to the increases experienced by patients who panicked with lactate.

Platelet monoamine oxidase (MAO) activity was studied in 21 patients meeting Research Diagnostic Criteria for panic disorder and in 12 healthy controls. Platelet MAO activity in females in both patient and control groups tended to be higher than that in males, but the results did not reach statistical significance. Platelet MAO activity was significantly decreased in panic disorder patients compared to controls.

The frequency and severity of separation anxiety for subjects with panic disorder and major depression was compared with that for normal controls. The subjects were diagnosed according to DSM-III criteria. Each subject completed a questionnaire consisting of 9 items derived from DSM-III criteria for separation anxiety disorder. The incidence of separation anxiety and its severity were significantly higher for the panic disorder subjects than for normal controls but there was no significant difference between depressed and panic disorder subjects. Panic disorder subjects with a history of separation anxiety disorder had a significantly earlier onset of panic attacks.

Preinfusion anxiety, heart rate, and blood pressure were measured in 31 normal subjects who received sodium lactate infusions. Eight subjects developed symptoms of panic anxiety during these infusions. Preinfusion anxiety as measured by psychologic symptoms of anxiety on the Panic Description Scale was significantly higher in the panickers while heart rate and blood pressure were not.

Seventy panic disorder patients participated in a double-blind, placebo-controlled, randomized infusion study in which sodium lactate and isoproterenol were used to induce panic anxiety. Patients who panicked during lactate, isoproterenol, and placebo infusions generally had higher preinfusion anxiety scores. These findings held true irrespective of the order the infusions were given. Stepwise multiple regression analyses comparing panickers with nonpanickers as the criterion variable revealed that the items "afraid of going crazy," "feeling unsteady," and "feeling paralyzed" on the Panic Description Scale had the highest predicting values.

The efficacy of buspirone for panic disorder was tested in 60 patients who met Diagnostic and Statistical Manual of Mental Disorders (3rd ed.) criteria for panic disorder or agoraphobia with panic attacks. Patients were randomly assigned to treatment with buspirone (mean dose 29.5 mg/day), imipramine (mean dose 140 mg/day), or placebo, and treated for 8 weeks after a 4- to 7-day placebo lead-in period. Patients with 4 or fewer attacks per month and those without attacks at the baseline visit were excluded from panic frequency comparisons. Both buspirone and imipramine tended to be better than placebo on total number of panic attacks, global psychopathology, and the Hamilton Anxiety rating scale, but end point differences among treatments were not statistically significant. At the end of the study, 25% of the buspirone patients were panic-free, as were 7% of the imipramine patients and 14% of the placebo patients; again, these differences were not statistically significant. The results of this study were inconclusive, partly because of the relatively small number of patients (10-11) completing the study in each treatment group, and partly because of a robust placebo response in this population. Possible reasons for this high placebo response are discussed, as well as suggestions for changes in study design for future studies.

We compared the responses of bulimic subjects to those of panic disorder patients and normal controls during infusions of sodium lactate and isoproterenol in a double-blind, placebo-controlled study. Four of 8 bulimics infused with lactate had panic attacks. Three of 9 bulimics infused with isoproterenol panicked, and 1 bulimic panicked with a placebo infusion. Although bulimics were less likely than panic disorder patients to panic during provocative infusions, their anxiety levels as measured by a panic description scale were as great. A large portion of the anxiety response in bulimics occurred in those who had concurrent panic attacks.

Eleven of 45 normal control subjects experienced panic attacks during lactate and/or isoproterenol infusions. Ten of the 11 subjects were followed up for a mean period of 32.5 months. Two subjects reported the development of spontaneous panic attacks during the follow-up period; one related the development of these attacks to the infusion experience. Neither subject met DSM-III criteria for panic disorder either before or after the infusions. Twenty-six healthy control subjects who did not experience panic attacks during the infusion experience did not report any attacks during a follow-up period of 31.1 months.

A history of thyroid dysfunction has been reported in patients with phobic disorders. There is also evidence of a blunted TSH response to TRH stimulation in patients with panic disorder. In this study, values of T3, T4 and T7 were compared between 26 patients with panic attacks and 20 normal controls. Patients were diagnosed according to DSM-III criteria and those with a clinical history of thyroid dysfunction were excluded. Patients were not on any medication when the blood samples were drawn. The mean values of T3, T4 and T7 did not significantly differ between the two groups, suggesting no evidence of hypo or hyperthyroidism; however, the variance of distribution of T3, T4 and T7 values was significantly different between the two groups (Fmax values for T3: 2.55, p value less than 0.05; T4: 3.15, p value less than 0.01; T7: 2.55, p value less than 0.05).

Eighty-six panic disorder patients and 45 nonpsychiatric controls were infused with isoproterenol at a rate of 1 microgram/min for up to 20 min in a placebo-controlled, double-blind study. Sixty-six percent of panic disorder patients experienced panic attacks during isoproterenol infusions, compared to 16% during placebo infusions. Nine percent of control subjects panicked with isoproterenol, but none panicked with placebo. Patients were more sensitive than controls to the anxiogenic effects of isoproterenol, as measured by subject self-ratings on a panic description scale. The frequency of panic attacks induced in patients was related to the dosage of isoproterenol; 79% of the patients who received a mean of 18.5 ng/min/kg of isoproterenol panicked. The panic attacks experienced by patients during isoproterenol infusions were similar to those experienced during placebo infusions.

To investigate the relationship between naturally occurring and drug-induced panic attacks, we compared the phenomenology of panic attacks in 12 panic disorder patients who panicked during both placebo and lactate infusion and in 9 panic disorder patients who panicked during both placebo and isoproterenol infusions. Panic attacks during lactate and isoproterenol infusions were similar to the panic attacks during placebo infusions.

The authors infused 45 control subjects with sodium lactate. Eight of 10 subjects with lactate-induced panic attacks and 26 of 35 without panic attacks were interviewed. An investigator, blind to the outcome of the infusion study, obtained family histories of 160 relatives. There was a high prevalence of anxiety disorders among first-degree relatives of subjects with panic attacks. There was no significant difference in the prevalence of mood disorders and substance abuse between first-degree relatives of subjects with (N = 45) and without (N = 115) panic attacks. The results suggest that individuals with a family history of anxiety disorders may be vulnerable to lactate-induced panic attacks.

Increases in the anxiety ratings, heart rate, and systolic and diastolic blood pressure were compared in eight panicking and 57 nonpanicking panic disorder patients during placebo (dextrose) infusions. Heart rate and systolic and diastolic blood pressure increased significantly in placebo-infused panickers, but these increases did not correlate well with increases in anxiety.

Baseline and preinfusion heart rates of 13 panic disorder patients who panicked during a placebo infusion were not significantly different from those of 57 panic disorder patients who did not panic during a placebo infusion. The change in preinfusion heart rates from baseline values also was not significantly different between the two groups.

Eight panic disorder patients participated in a double-blind placebo-controlled infusion study designed to induce panic-anxiety in the laboratory both before and after treatment with tricyclic antidepressants. Pre-infusion heart rates for the first infusion were significantly higher than baseline both before and after treatment. The delta increase in pre-infusion heart rates from baseline and the ratios of pre-infusion heart rates to baseline values were not significantly different between before and after treatment conditions indicating similar levels of arousal during the two pre-infusion periods, while the pre-infusion anxiety ratings after treatment were significantly lower.

Fourteen patients with panic disorder were infused with sodium lactate both before and after treatment with tricyclic antidepressants. All patients had panic attacks before treatment, and only five after treatment. There was a significant decrease in measures of anxiety prior to and during infusions after treatment. The patients were able to tolerate more lactate during reinfusions. The comparison of reinfusion panickers and nonpanickers revealed that the reinfusion panickers had higher levels of anxiety, as measured by psychological symptoms on the Panic Description Scale, during both their pretreatment and posttreatment infusions. Tricyclic antidepressants appear to increase the threshold for lactate-induced panic attacks.

Resting and pre-infusion heart rates recorded in 66 panic disorder patients revealed no significant differences between panickers and nonpanickers. There was also no significant difference in pre-fusion heart rates between either lactate or isoproterenol panickers and placebo nonpanickers. There was neither a sensitizing nor a desensitizing effect of laboratory-induced panic attacks on subsequent pre-infusion heart rates.

The effects of infusion-induced panic-anxiety on subsequent pre-infusion anxiety ratings and infusion-induced panic attacks were studied in 64 panic disorder patients, in a double-blind randomized study using sodium lactate, isoproterenol, and placebo infusions. While there was a decrease of preinfusion anxiety from one infusion to the next infusion both for panickers and nonpanickers, there was no evidence of either a significant decrease or an increase in the frequency of subsequent panic attacks. These results suggest that there is neither a desensitizing nor a sensitizing effect of pharmacologically induced panic attacks on subsequent infusions in a serial three-infusion design.

Three patients with a history of panic disorder and one patient with a history of generalized anxiety disorder were treated with buspirone and experienced an increase in their anxiety levels, agitation, and restlessness and also developed pressured speech and racing thoughts. These symptoms completely resolved after buspirone was discontinued. Jitteriness may have been due to an unusual adrenergic sensitivity in these patients.