Neurobiological mechanisms of panic anxiety: biochemical and behavioral correlates of yohimbine-induced panic attacks

The effects of yohimbine, an alpha 2-adrenergic receptor antagonist, on anxiety, blood pressure, heart rate, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and cortisol were determined in 20 healthy subjects and 68 patients who had agoraphobia with panic attacks or panic disorder. Yohimbine produced panic attacks meeting DSM-III criteria in 37 patients and one healthy subject. The patients reporting yohimbine-induced panic attacks had significantly larger increases in plasma MHPG, cortisol, systolic blood pressure, and heart rate than the healthy subjects. These findings support the hypothesis relating high noradrenergic neuronal activity to the pathophysiology of panic attacks in a subgroup of panic disorder patients.     

Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks

The therapeutic response to phenelzine sulfate was evaluated during 6 months' treatment of 35 outpatients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks. The possible influence of nonspecific predictors of drug efficacy and some biochemical parameters were investigated. Therapeutic response was assessed on standardized rating scales. Agoraphobic patients showed a significantly higher frequency of panic attacks when compared to the subjects with uncomplicated panic disorder. Phenelzine treatment blocked panic attacks in 100% of the patients with panic disorder and in 94.7% of the agoraphobics. Anticipatory anxiety and avoidant behavior improved markedly, although not statistically significantly, in 73.6% of the agoraphobics.     

Childhood separation anxiety and panic disorder: a comparative study

1. The relationship between childhood separation anxiety and panic disorder in adults is analyzed using data from a multicenter trial in 107 patients. 2. The patients included in this study presented anxiety disorder with or without agoraphobia, diagnosed according to DSM-III criteria. 3. The percentage of patients with antecedents of separation anxiety was 17.8% in patients without agoraphobia and 21.7% in patients with agoraphobia. These rates are significantly higher than those encountered in a group of normal controls (4%). 4. The existence of separation anxiety in childhood does not seem to significantly modify the clinical manifestations or severity of panic disorder in the adult.     

Benzodiazepine treatment of panic disorder: a comparison of alprazolam and lorazepam

The antipanic efficacy of alprazolam and lorazepam was evaluated in 48 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder in a double-blind random assignment study. On the basis of rating scale scores, both drugs demonstrated similar efficacy in reducing panic attacks and phobic behavior compared with placebo baseline. The doses required to achieve response were approximately double those required for the treatment of generalized anxiety. These results suggest that most, if not all, benzodiazepines may be effective antipanic drugs at high doses. The implications of these findings for drug treatments of choice for recurrent panic attacks are discussed.     

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.     

Increased anxiogenic effects of caffeine in panic disorders

The effects of oral administration of caffeine (10 mg/kg) on behavioral ratings, somatic symptoms, blood pressure and plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and cortisol were determined in 17 healthy subjects and 21 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder. Caffeine produced significantly greater increases in subject-rated anxiety, nervousness, fear, nausea, palpitations, restlessness, and tremors in the patients compared with healthy subjects. In the patients, but not the healthy subjects, these symptoms were significantly correlated with plasma caffeine levels. Seventy-one percent of the patients reported that the behavioral effects of caffeine were similar to those experienced during panic attacks. Caffeine did not alter plasma MHPG levels in either the healthy subjects or patients. Caffeine increased plasma cortisol levels equally in the patient and healthy groups. Because caffeine is an adenosine receptor antagonist, these results suggest that some panic disorder patients may have abnormalities in neuronal systems involving adenosine. Patients with anxiety disorders may benefit by avoiding caffeine-containing foods and beverages.     

Phobic disorders and anxiety states: how do they differ?

A review of the clinical literature to date has shown that the nature of the relationship between phobic disorders and anxiety states is still unclear. As a wide range of symptoms are shared by patients with all DSM-III anxiety disorder diagnoses, at this stage there is still a need to investigate the latent dimensions which distinguish the anxiety disorder subtypes. In the present study 176 patients with the DSM-III diagnoses of agoraphobia with panic attacks, social phobia, panic disorder and generalized anxiety disorder completed the Fear Survey Schedule, Fear Questionnaire, Hostility and Direction of Hostility Questionnaire, Maudsley Personality Inventory, and the Hamilton Anxiety and Depression Scales. Group membership was significantly predicted by a discriminant analysis which yielded a Fear Questionnaire agoraphobia function and a social phobia function. The results from discriminant analysis suggests that agoraphobia and anxiety states may be closely related. Classification errors were also determined, providing further evidence with which to refute the claim that agoraphobia has "all or none" characteristics.     

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.     

History of separation anxiety in patients with panic disorder and depression and normal 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.     

Panic attacks and related disorders in alcohol-dependent, depressed, and nonclinical samples

Although several studies have indicated that a substantial portion of alcoholics have an anxiety disorder, relatively little information exists specifically regarding panic disorders. In addition, prior studies have been marred by the absence of appropriate contrast groups. The present investigation compared the lifetime prevalence of panic attacks and panic-related disorders diagnosed according to DSM-III criteria in a group of 79 alcohol-dependent patients, 64 depressed patients, and 70 nonclinical subjects. Panic attacks, panic disorder, and agoraphobia with panic attacks were more prevalent in the alcohol-dependent and depressed samples than among nonclinical subjects. Men in both clinical samples were more likely than women to have had nonagoraphobic panic disorder, but male alcoholics were less likely to have developed agoraphobia than were female alcoholics or depressed patients of either sex. No consistent chronological relationship between onset of panic attacks and alcohol abuse was found. Results indicate that there is an unusually high prevalence of panic attacks and panic-related disorders among alcoholics, but comparable prevalence rates can be found in depressed and perhaps some other psychiatric populations. Implications for the assessment and treatment of alcohol-dependent and panic-disordered patients are discussed.     

Noradrenergic function and the mechanism of action of antianxiety treatment. II. The effect of long-term imipramine treatment

Considerable preclinical and clinical evidence indicates that increased noradrenergic function is involved in the development of anxiety. Imipramine hydrochloride, which has complex effects on noradrenergic function in animals, is effective in patients with agoraphobia and panic disorder. To assess the effects of imipramine on noradrenergic function in patients, plasma levels of free 3-methoxy-4-hydroxyphenylglycol (MHPG) and yohimbine-induced increases in plasma MHPG levels, anxiety-nervousness, blood pressure, and somatic symptoms were studied before and during long-term imipramine treatment in 11 patients meeting DSM-III criteria for agoraphobia with panic attacks. Long-term imipramine treatment significantly decreased baseline plasma MHPG levels by 38% and modestly potentiated yohimbine-induced increases in blood pressure, but it did not alter yohimbine-induced increases in plasma MHPG levels or in patient ratings of anxiety-nervousness. The therapeutic effects of imipramine in panic disorder may relate more to the decrease in norepinephrine turnover than to alterations of alpha 2-adrenergic autoreceptor function.     

Phenomenology of panic attacks: a descriptive study of panic disorder patients' self-reports

The phenomenology of panic disorder and panic attacks was systematically assessed in 46 consecutive patients. The results suggest that DSM-III criteria include several symptoms that are not frequently present during a panic attack and that DSM-III's characterization of a panic attack is imprecise and misleading. Panic attacks were found to vary in intensity, frequency, spontaneity, and associated symptoms. A panic attack typically presents as a unified symptom complex of psychic anxiety and multiple somatic symptoms in multiple body systems. It occurs in a crescendolike pattern, is self-limited, and often leaves the subject weak or shaken. The temporal course as much as the symptomatic presentation defines a panic attack.     

A comparison of DSM-III personality disorders in panic/agoraphobia and obsessive-compulsive disorder

One hundred eighty-seven patients meeting DSM-III criteria for panic disorder (161 with agoraphobia) and 51 patients meeting DSM-III criteria for obsessive-compulsive disorder (OCD) were assessed with the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess axis II personality disorders and traits. The results showed that the personality profiles were similar between the two diagnostic groups and that the major personality characteristics identified in panic/agoraphobic patients, e.g., avoidant, dependent, histrionic, and borderline, were more pronounced in patients with OCD. These findings support our earlier suggestion of a nonspecific link between panic disorder/agoraphobia and personality disorder (PD)/traits.     

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. II. Patient acceptance, side effects, and safety

In a multicenter placebo-controlled study, the safety, side effects, and patient acceptance of alprazolam for the treatment of panic disorder and agoraphobia were examined. A total of 525 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder were randomly assigned to receive alprazolam or placebo, which they took for eight weeks. The mean daily dose at the end of the study was 5.7 mg of alprazolam or 7.5 capsules of placebo daily. Potentially serious reactions to alprazolam occurred in ten of 263 subjects who received the drug. These included acute intoxication (three), hepatitis (two), mania (two), amnesia (one), aggressive behavior (one), and depression (one). Treatment-related side effects that were worse in patients taking alprazolam than in those taking placebo included sedation, fatigue, ataxia, slurred speech, and amnesia. Sedation was the most frequent but tended to subside with dose reduction or continued administration of the drug. Patient acceptance of alprazolam, as measured by the rate of completion for study participants, was high. Eighty-four percent of patients receiving active drug completed the study compared with 50% receiving placebo.     

Correlates of DSM-III personality disorder in panic disorder and agoraphobia

One hundred eighty-seven patients meeting DSM-III criteria for panic disorder (n = 26) or agoraphobia with panic (n = 161) were assessed with the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess Axis II personality disorders and traits. Results replicated our earlier findings of a preponderance of dependent, avoidant, and histrionic features and the finding that patients exhibiting a greater number of personality traits were also significantly more symptomatic. Patients with the diagnosis of panic disorder did not differ on any personality disorder variables from patients with the diagnosis of agoraphobia with panic. Furthermore, none of the specific symptom dimensions, i.e., panic, anxiety, or agoraphobia, was selected as a unique predictor of any personality variables in the regression analyses. Rather, the most important correlates of personality disorder in these patients consisted of general factors such as dysphoric mood, social phobia, or interpersonal sensitivity, and Eysenck's neuroticism dimension. The results are discussed in light of recent findings suggesting a nonspecific link between panic disorder or agoraphobia and personality disorder.     

Low dose desipramine treatment of cocaine-related panic attacks.

Thirteen patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia that started during or shortly after cocaine exposure were treated in the UCLA Anxiety Disorders Program (Los Angeles, CA). Low starting doses (ranging from 2.5 to 10 mg/day) of desipramine were used. Doses were then slowly increased to an average daily dose of 25 mg. Eleven patients who were able to tolerate an initial increase in panic anxiety responded to this treatment strategy with almost full resolution of panic attacks. The authors discuss the possible value and mechanisms of low dose treatment of cocaine-related panic attacks.     

Cognitive-behavioral therapy for panic: an open study

This paper reports results of an open prospective study of 26 patients who met DSM-III criteria for panic disorder or agoraphobia with panic attacks. Cognitive-behavioral treatment alone produced clinically and statistically significant improvement in panic symptoms, including both full-blown and limited symptom episodes. In addition, the treatment produced improvement in associated symptoms of phobic avoidance and generalized anxiety. This work provides further preliminary indication of the usefulness of cognitive-behavioral strategies as an alternative to medication in symptom-oriented treatments.     

The relationships among separation anxiety disorder,adult attachment style and agoraphobia in patients with panic disorder

Epidemiological studies indicate that separation anxiety disorder occurs more frequently in adults than children. It is unclear whether the presence of adult separation anxiety disorder (ASAD) is a manifestation of anxious attachment, or a form of agoraphobia, or a specific condition with clinically significant consequences. We conducted a study to examine these questions. A sample of 141 adult outpatients with panic disorder participated in the study. Participants completed standardized measures of separation anxiety, attachment style, agoraphobia, panic disorder severity and quality of life. Patients with ASAD (49.5% of our sample) had greater panic symptom severity and more impairment in quality of life than those without separation anxiety. We found a greater rate of symptoms suggestive of anxious attachment among panic patients with ASAD compared to those without ASAD. However, the relationship between ASAD and attachment style is not strong, and adult ASAD occurs in some patients who report secure attachment style. Similarly, there is little evidence for the idea that separation anxiety disorder is a form of agoraphobia. Factor analysis shows clear differentiation of agoraphobic and separation anxiety symptoms. Our data corroborate the notion that ASAD is a distinct condition associated with impairment in quality of life and needs to be better recognized and treated in patients with panic disorder.     

Childhood and family characteristics in panic and generalized anxiety disorders

The author compared 32 patients who had generalized anxiety disorders with 29 patients who had panic disorder and agoraphobia with panic attacks. He observed that patients with generalized anxiety disorder more often had lost their fathers and/or mothers before the age of 16 years, whereas patients with panic disorder and agoraphobia with panic attacks had more often experienced chronic anxiety in childhood. More parents and siblings of patients with panic disorder had affective disorders and alcohol abuse than did parents and siblings of patients with anxiety disorders.