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Biomedical subjects

R Noyes

Publications and source records attributed to R Noyes.

At least 91 records · Page 5Linked to original sources

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.

Adult↗

Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment.

Depressive symptomatology in 481 subjects with panic disorder and phobic avoidance was studied as part of an investigation of the efficacy of alprazolam in panic disorder. Subjects who had a major depressive episode (MDE) before the onset of their panic disorder were not included in the trial. With this exclusion criterion, 31% of subjects had a secondary MDE occurring after the onset of the panic disorder. The occurrence of secondary MDE was related to the length of time subjects were ill with panic disorder. Compared with the subjects without depression, those subjects with current MDE had higher scores on measures of anxiety and depression but not on the number of panic attacks per week. The presence of depression and the degree of phobic avoidance contributed independently to measures of the severity of the panic illness. Alprazolam was effective in reducing panic and depressive symptomatology in both depressed and nondepressed subjects with panic disorder. The presence of an MDE was not predictive of the outcome of treatment for the panic and phobic symptoms. Subjects with or without depression responded similarly to alprazolam.

Adult↗

HPA axis disturbance and treatment outcome in panic disorder.

Some patients with panic disorder exhibit an abnormal response to dexamethasone. As this phenomenon may reflect disturbances in the central noradrenergic system and as alprazolam may work through this system to produce improvement, we predicted a particularly robust response among nonsuppressors. Fifty-two patients with panic disorder or with agoraphobia with panic attacks were given alprazolam as the sole treatment during either of 2, 8-week, double-blind, placebo-controlled trials. Though baseline clinical severity predicted globally rated outcome, baseline Dexamethasone Suppression Test results did not.

Adult↗

Relationship of urinary free cortisol levels in patients with panic disorder to symptoms of depression and agoraphobia.

Sixty-five patients with panic disorder and 37 matched controls collected 24-hour urine specimens for measurement of urinary free cortisol. Although patients with panic disorder had significantly higher urinary free cortisol levels than control subjects, this difference was accounted for by panic disorder patients with concomitant depression, agoraphobia, or both. Urinary free cortisol excretion was not related to the age of onset of panic disorder, the number of spontaneous panic attacks, or the degree of impairment associated with the disorder. They were related, however, to the level of symptoms on both the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety in the entire group of panic patients, but this relationship disappeared when those patients with the complications of agoraphobia and depression were excluded. These data suggest that, as with primary depression, depression secondary to panic disorder, as well as to agoraphobia in panic disorder patients, is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis.

Adult↗

Anxiety symptoms distinguishing social phobia from panic and generalized anxiety disorders.

Social phobic (N = 14), generalized anxiety disorder (N = 18), and panic disorder patients (N = 48) were compared on four categories of anxiety symptoms: autonomic hyperactivity, muscular tension, vigilance, and apprehensive expectation. Six specific symptoms (palpitations, chest pains, tinnitus, blurred vision, headaches, fear of dying, and dry mouth) distinguished social phobia from panic disorder, while four (headaches, fear of dying, sweating, and dyspnea) distinguished social phobia from generalized anxiety disorder. Most symptom differences were in the autonomic hyperactivity category of symptoms. These findings further confirm the validity of social phobia as a distinct disorder and may help provide specific target symptoms for the treatment of related but different anxiety disorders.

Adolescent↗

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.

Adult↗

Benzodiazepine withdrawal: a review of the evidence.

In a recent series of controlled studies, investigators looked at what happened when benzodiazepines were discontinued. Despite methodological problems, these studies showed that rebound anxiety occurred in a substantial minority of patients after several weeks of drug use. Also, a withdrawal syndrome developed in nearly half of patients who used benzodiazepines for more than a year. In these studies, risk factors included dose, duration of use, elimination rate of the drug, and abruptness of discontinuation. Patients who are physically dependent on benzodiazepines may need help in stopping these agents. Physicians should advise gradual discontinuation and, along with emotional support, should consider the use of alternative medications for the control of symptoms.

Anti-Anxiety Agents↗

Similarities in hypothalamic-pituitary-adrenal axis activity between patients with panic disorder and those experiencing external stress.

Psychologic stressors are less potent stimuli of the HPA axis in humans than physical stressors, but they can cause mild changes in acute ACTH and cortisol production. These changes, however, are generally not of sufficient magnitude or duration to cause measurable changes in UFC excretion. Furthermore, chronic stress leads to an attenuation of the HPA axis response. This basic knowledge concerning psychologic stress helps explain the reason why patients with uncomplicated anxiety/panic disorder, a condition involving similar symptoms, do not demonstrate UFC abnormalities. Panic disorder, when accompanied by depression, however, is associated with an increase in UFC excretion which is probably more related to the depression than the panic state. Interestingly, panic disorder, when accompanied by agoraphobia, also shows an elevation in UFC levels which makes it endocrinologically distinct from uncomplicated panic disorder. The reason for this is unclear. Treatment of the panic disorder with benzodiazepines does not further lower the UFC levels in patients with uncomplicated panic disorder despite clinical improvement, but it does lower UFC levels into the normal range in those with concurrent depression and agoraphobia. Alteration in the UFC level with treatment is only partially related to clinical improvement.

Agoraphobia↗

A linkage study of panic disorder.

We tested for linkage between panic disorder and a battery of 29 genetic markers in 26 families. Linkage between panic disorder and 18 of the marker loci could be excluded at a recombination fraction of 0.00, nine at a recombination fraction of 0.05, and four at a recombination fraction of 0.10. The 18 loci are distributed over ten chromosomes. One locus was suggestive of linkage. The maximum lod score for alpha-haptoglobin was 2.27 at a recombination fraction of 0.0, representing odds in favor of linkage of 186.1. alpha-Haptoglobin has been mapped to chromosome 16q22. The results demonstrate that linkage studies of psychiatric disorders can yield informative results by identifying tentative linkages that merit further investigation and by excluding regions of the genome from future linkage searches.

Adult↗

State and personality in depressed and panic patients.

The authors examined 36 patients with panic disorder, 66 patients with major depression, and 124 control subjects to determine personality differences between them in the ill and the recovered states. The panic and depressed groups did not differ from each other in either state. Both recovered groups had less emotional strength and greater interpersonal dependency than the control subjects. The effect of state on personality measures appears to be similar for anxious and depressed patients. No personality measures that clearly differentiated the recovered panic and depressed patients were found.

Acute Disease↗

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.

Adult↗

A family study of generalized anxiety disorder.

The frequency of generalized anxiety disorder was higher among first-degree relatives of probands with generalized anxiety (N = 20) than among the relatives of control subjects (N = 20), but it was not higher among relatives of probands with panic disorder (N = 40) or agoraphobia (N = 40). Also, the frequency of panic disorder was higher among relatives of probands with panic disorder than among control relatives but was not higher among relatives of generalized anxiety probands. Relatives of probands with generalized anxiety who had the same disorder had a mild, stress-related illness. The results confirm the separation between generalized anxiety disorder and panic disorder but challenge the distinction between generalized anxiety and adjustment disorders.

Adjustment Disorders↗

Desipramine: a possible treatment for depersonalization disorder.

Primary depersonalization disorder is believed to be resistant to treatment. However, we report the successful treatment of a case with desipramine and suggest that, because there is a link between depersonalization and anxiety disorders, tricyclic antidepressants may prove effective for depersonalization.

Adolescent↗

Factors associated with motor vehicle accidents among male alcoholics.

Male alcoholics (N = 260) presenting for inpatient treatment were given a structured psychiatric interview that included questions about previous motor vehicle accidents while intoxicated. The histories of 57 patients who reported personal injury accidents were compared with those of 131 patients who did not report accidents. Patients reporting accidents were more severely ill and had an earlier onset of heavy drinking. Also, more patients with accidents belonged to a subgroup of alcoholics with antisocial personality. The identification of high-risk alcoholics may contribute to motor vehicle accident prevention.

Accidents, Traffic↗

Generalized anxiety disorder.

Generalized anxiety disorder is a relatively new clinical entity and current understanding of this syndrome lacks a solid research base. However, useful generalizations can be derived from earlier studies of anxiety neurosis and other previously defined anxiety syndromes. Most persons with GAD are seen by primary care physicians, but recognizing these patients may be difficult. In the primary care setting they often present with physical complaints suggesting a specific organ system disease. Depression and substance abuse may be presenting problems in patients with primary GAD. Primary care physicians are usually able to provide appropriate care for generalized anxiety disorder patients. By keeping in mind the cognitive, behavioral, affective, and physiologic aspects of the syndrome, they can appropriately address the specific therapeutic needs of individual patients. The nature of the doctor-patient relationship in primary care favors the development of therapeutic trust that is important for effective management of GAD. Drug therapy is a useful adjunct in the treatment of many patients with GAD. However, the use of drugs as the sole therapeutic modality is seldom appropriate.

Adult↗

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.

Adult↗