Sleep complaints in panic disorder patients

Patients with anxiety disorders often report difficulty sleeping. The present study assesses the prevalence of sleep complaints in panic disorder (PD) patients, compares them with sleep complaints in a normal population, and investigates the role of comorbid depression and nocturnal panic attacks in sleep complaints in the PD patients. Seventy PD patients and 70 healthy controls were asked about their subjective sleep characteristics by means of the Sleep-Wake Experience List, which assesses sleep/arousal complaints over a 24-hour period. Sixty-seven percent of the PD patients reported sleep complaints, compared with 20% of the controls. Eighty-six percent of the depressed PD patients and 59% of the nondepressed had sleep difficulties; 77% of the PD patients with nocturnal panic attacks reported sleep complaints, versus 53% of the PD patients without nocturnal panic. It is concluded that PD patients demonstrate a higher prevalence of sleep complaints than normal controls; this can only partly be explained by comorbid depression, and cannot be explained by the presence of nocturnal panic attacks.     

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.     

Electroencephalography during sleep of patients with panic disorder

Sleep electroencephalograms (EEGs) of subjects with primary panic disorder were compared to those of normal controls matched for age and sex. Significant differences were found between patients and controls in sleep latency, sleep efficiency, and stage 2 sleep duration. No differences were found between the two groups in REM latency. Because depressed patients are known to have reduced latency to REM sleep, these data add support to the hypothesis that panic disorder and depression are distinct disorders.     

Behavioral and physiologic effects of short-term and long-term administration of clonidine in panic disorder

We evaluated the behavioral and physiologic effects of clonidine hydrochloride, a centrally active alpha 2-adrenergic agonist, in two separate studies of patients with panic disorder. In the first study, intravenous clonidine (2 micrograms/kg) and placebo were administered on a blind basis to 12 patients with panic disorder and ten normal controls. Clonidine produced significantly greater decrements in anxiety at one hour in the patients with panic disorder than in the controls. The changes in pulse, blood pressure, and ratings of sleepiness did not differ significantly between patients and controls. In the second study, oral clonidine was administered to 18 patients in a double-blind, flexible-dose treatment trial averaging ten weeks in duration. While anxiolytic effects were noticed in some patients, these effects did not persist in the group as a whole. These two studies indicate that while clonidine has short-term anxiolytic effects in patients with panic disorder, these effects do not persist with long-term administration in most patients.     

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.     

Retrospective reports of parenting in depressed adults with and without comorbid panic disorder and social anxiety disorder

Previous research has examined the role of parenting in the development of depression and anxiety disorders using retrospective reports of parenting behaviors. However, most studies have not considered comorbidity; the few that have did not differentially examine individual anxiety disorders and yielded inconsistent results. The present study compared retrospective parenting reports given by depressed individuals with no comorbid anxiety disorder, comorbid panic disorder, and comorbid social anxiety disorder. Results indicated that depressed men with panic disorder reported significantly greater maternal and nonsignificantly greater paternal protectiveness than depressed men without panic disorder but not than depressed women with and without panic disorder. No differences were found for the retrospective parenting reports given by depressed participants with or without social anxiety disorder. This work highlights the importance of examining specific anxiety disorders rather than grouping all depressed patients with any anxiety disorder together, as well as examining males and females separately when investigating the influence of parental behavior.     

The sleep of non-depressed patients with panic disorder: a comparison with normal controls

Arriaga F, Paiva T, Matos-Pires A, Cavaglia F, Lara E, Bastos L. The sleep of non-depressed patients with panic disorder: a comparison with normal controls. Acta Psychiatr Scand 1996: 93: 191–194. © Munksgaard 1996. All-night sleep EEG recordings were performed in non-depressed patients with panic disorder, agoraphobia, and a group of age- and sex-matched normal controls. Patients were selected according to DSM-IV and all subjects were studied under drug-free conditions. In addition to sleep continuity disturbances, patients with panic disorder have a reduced percentage of slow wave sleep, mainly due to diminished amounts of stage 4. REM sleep characteristics are identical in the two groups. When depressive co-morbidity and non-specific causes of insomnia are excluded, the sleep EEG of panic patients seems to be characterized by modest changes in sleep continuity and sleep architecture. These findings favour the existence of a neurophysiological frontier between anxiety disorders and depressive illness.     

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.     

Twenty-four hour skin conductance in panic disorder

Skin conductance, physical activity, ambient temperature and mood were recorded for 24 h in 22 panic disorder (PD) patients and 29 healthy controls. During the day, subjects performed standardized relaxation tests (ARTs). We hypothesized that tonically elevated anticipatory anxiety in PD during waking and sleeping would appear as elevated skin conductance level (SCL) and greater skin conductance (SC) variability. Mean SCL was higher during both usual waking activities and sleeping in PD, but not during the ARTs. Group SC variability differences did not reach significance, perhaps because of variance unrelated to anxiety. Analyses indicated that in the PD group, antidepressant medication reduced mean SCL whereas state anxiety had the opposite effect during the day. Depressive symptoms reported during the day were related to elevated mean SCL on the night of the recording. The rate and extent of SCL deactivation over the night was equal in the two groups. However, PD patients had more frequent interruptions of deactivation that could have arisen from conditioned arousal in response to threat cues during sleep.     

Lactate- and isoproterenol-induced panic attacks in panic disorder patients and controls

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 imipramine binding in patients with panic disorder and major familial depression

Platelet 3H-imipramine binding was investigated in 15 normal subjects, 17 patients with major depressive disorder and 43 patients with panic disorder, to further study the relationship between depressive and anxiety disorders. Whereas patients with major depression had a significantly lower mean Bmax value than healthy volunteers, mean Bmax values in patients with panic disorder did not differ significantly from normal controls. Furthermore, apparently normal Bmax values were observed even in those panic disorder patients who had concurrent major depression or a past history of depression. Thus, despite previous findings of an overlap between panic and depressive disorders, the present results suggest that the two syndromes may have distinct neurochemical substrates.     

Effect of a novel environment on resting heart rate in panic disorder

Several studies have found higher resting heart rate among patients with panic disorder compared to healthy controls, whereas others have found no differences. It has been suggested that these differences may result from anticipatory anxiety. The purpose of this study was to compare the resting heart rates of 10 patients with panic disorder, 11 patients with social phobia, and 13 healthy controls during two consecutive visits to our laboratory. There were no significant differences between groups on resting heart rate on either day. However, patients with panic disorder did have significantly higher resting heart rates on day 1 versus day 2. This suggests that patients with panic disorder may experience greater anticipatory anxiety which is manifested in a higher resting heart rate than patients with social phobia or healthy controls. Implications for previous and future reports on resting heart rate measures in patients with panic disorder are discussed. Depression and Anxiety 8:24–28, 1998. © 1998 Wiley-Liss, Inc.     

Urinary phenylacetic acid in panic disorder with and without depression

Phenylacetic acid (PAA) excretion was measured in 39 patients who met criteria for panic disorder; 9 of these also had major depression, and 30 did not. Patients with panic and depression excreted 66 +/- 23 mg/day of PAA, an amount significantly lower than in normal controls; patients with panic disorder but without depression excreted 104 +/- 23 mg/day of PAA (not significantly lower than controls). The results support previous studies indicating that PAA excretion is a marker for depressive disorder.     

Platelet [3H]imipramine binding in generalized anxiety disorder, panic disorder, and agoraphobia with panic attacks

The density of platelet [3H]imipramine binding sites is reported to be decreased in unipolar depression and, hence, is a putative biological marker. There is considerable evidence for a phenomenological and biological relationship of panic disorder with affective disorder. We studied platelet [3H]imipramine binding site density in unmedicated subjects with generalized anxiety disorder (GAD; n = 55), panic disorder (PD) with and without agoraphobia (n = 52), and normal controls (n = 26) in order to determine whether or not patients with panic disorder differed from controls in this biological assay. We found no differences in binding site density (Bmax) or affinity (Kd) among the PD, PD with agoraphobia, GAD, and control groups. Nor did we find a relationship between Bmax or Kd and the severity of depressive symptoms or the presence of a family history of affective disorder. In view of two conflicting prior studies, the use of [3H]imipramine binding in panic disorder remains problematic.     

The effects of physostigmine infusion on patients with panic disorder

Nine patients who met both DSM-III and RDC criteria for panic disorder and nine age-matched normal controls received infusions of physostigmine. The patients and normal controls did not differ in either their self-reported or the observer-reported ratings of anxiety, mood, or activation. The two subject groups also did not differ in blood pressure, pulse, or cortisol responses to physostigmine. Physostigmine did not provoke panic attacks in either the control or patients groups.     

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.     

Hypochondriacal concerns in panic disorder and major depressive disorder: a comparison

OBJECTIVE: To gain perspective on the relationship between hypochondriasis and panic disorder, we compared the occurrence of hypochondriasis in patients with panic disorder (N= 59) and major depressive disorder (N= 27). METHODS: Patients who participated in separate drug treatment trials were assessed at baseline and eight weeks using the Whiteley Index of Hypochondriasis. RESULTS: At baseline, the Whiteley Index score was greater for patients with panic disorder than for those with major depressive disorder. At eight weeks, a statistically significant reduction in the mean hypochondriasis score was observed in panic patients who had improved but not in major depressive patients who had improved. Modest correlations were observed between hypochondriasis and symptoms of panic and major depressive disorder, but in depressed patients, hypochondriasis was positively correlated with anxiety symptoms as well. CONCLUSION: A unique relationship appears to exist between hypochondriasis and panic disorder. The nature of this relationship and its implications for classification are discussed.     

Changes in anxiety sensitivity with pharmacotherapy for panic disorder

Fear of anxiety symptoms (anxiety sensitivity) has been implicated in the etiology and maintenance of panic disorder, and has been shown to improve with cognitive-behavioral treatment. The impact of pharmacotherapy on anxiety sensitivity is less clear. We administered the Anxiety Sensitivity Index (ASI) during a 12-week randomized controlled trial investigating the relative efficacy of paroxetine, paroxetine plus sustained clonazepam, and paroxetine plus brief clonazepam for patients with panic disorder. We found a mean reduction in ASI scores of 9.6 points, which correlated with symptomatic improvement, and did not differ significantly between groups. Our data provides further evidence that pharmacotherapy leads to significant acute reductions in fears of anxiety symptoms in patients with panic disorder, albeit at levels that may be somewhat less than the changes associated with CBT. Implications of these findings are discussed relative to optimizing pharmacologic treatment of panic disorder.     

Auditory evoked potentials in panic disorder.

Neuroimaging studies of behavioral-induced anxiety in non-patients and of lactate-induced anxiety in panic disorder patients have indicated that normal and pathological anxiety may share a common pathway involving the temporal poles. As panic-related anxiety may reflect faulty temporopolar evaluative processing of input, the objective of this study was to examine sensory reactivity in panic disorder patients via scalp recordings of the late auditory evoked 'vertex' potential (LAEP) which appears to have a predominantly temporal lobe origin. Twelve patients diagnosed according to DSM-III criteria as panic disorder and ten normal controls served as subjects in this study. EEG was recorded from 16 scalp sites using a monopolar fronto-occipital derivation and LAEPs were separately averaged in response to four acoustic intensities. Analysis focused on group and electrode-site differences in the negative (N1) and positive (P2) component amplitudes of the LAEPs. Panic disorder patients were found to exhibit significantly larger N1 amplitudes across all stimulus intensities and across all recording sites. No significant group differences were observed with P2. Although the results provide indirect support for a temporal focus, other modulating influences must be considered in data interpretation.     

Twenty-four hour growth hormone secretion in patients with panic disorder

BACKGROUND: Patients with panic disorder have blunted growth hormone (GH) responses to clonidine, suggesting subsensitivity of post-synaptic alpha(2)-adrenoreceptors, presumably in response to excessive central noradrenergic outflow. However, basal levels of GH release over a full circadian cycle have not been examined in panic. Reduced basal GH release would suggest an overall hypo-active GH system rather than a specific alpha-adrenergic abnormality. METHODS: To determine whether panic patients show reduced basal GH secretion, 20 patients and 12 healthy controls were studied. Blood samples were drawn every 15 min for 24 h and plasma was assayed for GH. Patients were restudied during successful treatment with alprazolam. Groups were compared on overnight and daytime GH secretion and circadian patterns of release. RESULTS: Patients showed normal levels on all measures of GH release. Treatment may have reduced nocturnal GH release slightly, but treated patients still did not differ from controls. The normal predominance of sleep over waking GH secretion was seen in both groups. CONCLUSIONS: Panic patients, in contrast to depressed patients, have normal somatotrophic axis activity when measured in a resting state over a full circadian cycle. GH dysregulation may only be evident in these patients in activation paradigms and has been most consistently demonstrated by challenges with the alpha(2)-noradrenergic agonist, clonidine.