Biomedical subjects
R Noyes
Publications and source records attributed to R Noyes.
Seizures following the withdrawal of alprazolam.
Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose for 10 weeks. A review of available case reports suggests that seizures, like other withdrawal phenomena, are more apt to occur with short-acting benzodiazepines. To prevent their occurrence these drugs should be discontinued gradually and consideration given to substituting long-acting drugs during the withdrawal period. Physicians should remain alert to the fact that seizures may occur as early as 24 hours after the abrupt withdrawal of short-acting benzodiazepines.
Mortality among outpatients with anxiety disorders.
An earlier follow-up of inpatients with panic disorder attributed excess mortality among men to death from unnatural causes and from cardiovascular disease. The present study sought to determine the stability of this finding with a 12-year follow-up of 155 outpatients with anxiety neurosis. As in the first study, men were twice as likely to die as expected, and this excess in deaths was attributable to cardiovascular disease and suicide. Given the small numbers in both studies, however, the link between panic disorder and excess cardiovascular mortality remains tentative.
The effect of state anxiety on personality measurement.
The authors examined the effect of state anxiety on the personality test scores of 56 patients receiving treatment for panic disorder and agoraphobia. The tests were administered before treatment and again 6 weeks later. For the 40 patients who improved by 5 or more points on the Hamilton Anxiety Rating Scale, significant changes in personality measures were observed at week 6, including increased emotional strength and extraversion and decreased interpersonal dependency. The authors conclude that state anxiety, like depression, is a possible confounding factor in personality measurement, and adjustment for it should be made in future studies.
Reduction in hypochondriasis with treatment of panic disorder.
Hypochondriasis was assessed in 60 patients with panic disorder and agoraphobia using the Illness Behavior Questionnaire. Before treatment, IBQ hypochondriasis scores were similar to those of a group of hypochondriacal psychiatric patients. In patients who improved with treatment, significant reductions in somatic preoccupation, disease phobia, and disease conviction occurred. Hypochondriasis appears to be a prominent feature of panic disorder and agoraphobia, and responds to treatment of the primary conditions. Our findings underscore the importance of providing adequate treatment and thereby avoiding wasteful use of medical resources and alienation of patients from doctors.
Pharmacologic treatment of phobic disorders.
Pharmacologic treatment of phobic disorders, in particular agoraphobia, has been proved to be effective, especially when used in combination with behavior therapy. Favorable responses to tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines have been reported. The limitations of drug therapy for phobias include high dropout rates and the tendency to relapse after discontinuation of therapy. Successful treatment depends on the careful selection of patients and medications and on coordination of drug and behavior therapies.
Depression and cancer.
Depression appears to be a frequent complication of neoplastic disease. Recent surveys suggest that it is not only a common reason for psychiatric referral but that a substantial minority of hospitalized cancer patients suffer from an affective disturbance severe enough to warrant psychiatric intervention. In view of its reported prevalence it is likely that this complication adversely affects the quality of patients' lives and interferes with the management of their disease. Given the nature of this problem it is disturbing that so little systematic research has been done, especially in the area of treatment. In this article we critically review the literature concerned with the relationship of depression to cancer. We begin with comment on the nature of the association between cancer and depression and the question of whether depression is an etiologic factor in neoplastic disease. Before considering the prevalence of affective disorders among cancer patients, we examine the difficulty of diagnosing depression in seriously ill patients. Next, we explore the role of various psychological and biological factors in the etiology of this complication and, finally, we offer recommendations for treatment and suggest directions for future research.
Tritiated imipramine binding to platelets is decreased in patients with agoraphobia.
Controversy exists regarding the relationship between anxiety states and major depression. We studied the binding of tritiated imipramine to platelet membranes in order to determine if patients with agoraphobia and panic attacks differed from depressed subjects or healthy volunteers on this biological parameter. Mean (+/- SD) Bmax and Kd values were significantly lower in patients with agoraphobia and panic attacks (787 +/- 276 fmole/mg protein and 0.35 +/- 0.14 nM, respectively) than in healthy volunteers (1237 +/- 201 fmole/mg protein and 0.71 +/- 0.37 nM, respectively). In addition, patients with agoraphobia and panic attacks had binding parameters that were similar to those of patients with bipolar or familial pure depressive disorder, but significantly lower than those of patients with depressive spectrum or sporadic depressive disorder. These findings have implications for both the nosology and pathophysiology of anxiety disorders.
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.
Motor vehicle accidents related to psychiatric impairment.
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A withdrawal syndrome after abrupt discontinuation of alprazolam.
A patient who received therapeutic doses of alprazolam for 8 weeks experienced a withdrawal syndrome beginning 18 hours after its abrupt discontinuation. Short-acting and minimally sedating benzodiazepines may have increased potential for withdrawal reactions.
Beta-adrenergic blocking drugs in anxiety and stress.
A series of controlled studies have demonstrated an antianxiety effect of beta-adrenergic blocking drugs in patients with anxiety. Also, in certain performance situations, beta-blocking drugs may block the autonomic response to stress and reduce anxiety. However, because these drugs are less effective than the benzodiazepines, their role in the treatment of anxiety and phobic disorders appears to be limited.
Diazepam and propranolol in panic disorder and agoraphobia.
The response to diazepam and propranolol hydrochloride was compared in 21 patients who (with one exception) met DSM-III criteria for panic disorder and agoraphobia. Each drug was administered for two weeks in double-blind fashion according to a crossover design. The response to diazepam was significantly superior on all measures. By observer rating, 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol. Panic attacks and phobic symptoms responded to diazepam, but not to propranolol. The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders.
Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.
The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.
A comparison of panic disorder and generalized anxiety disorder.
Subjects from a family study who had panic disorder and generalized anxiety disorder were compared on the pattern of their symptoms, age and type of onset, personality characteristics, course of illness, and outcome. Subjects with generalized anxiety disorder were shown to have fewer autonomic symptoms and an earlier, more gradual onset. Their illness was also observed to have a more chronic course and a more favorable outcome, although these differences were not statistically significant. The validity of generalized anxiety disorder and panic disorder as discrete diagnostic entities is supported.
Family study of agoraphobia. Report of a pilot study.
A family study of agoraphobia (n = 20), panic disorder (n = 20), and nonanxious controls (n = 20) showed the morbidity risk for all anxiety disorders to be 32% among first-degree relatives of agoraphobics, 33% among relatives of patients with panic disorder and 15% among relatives of controls. Relatives of agoraphobics were also shown to be at higher risk for alcohol disorders. Female relatives were found to be at greater risk for anxiety disorders, reflecting their increased susceptibility to these illnesses, and male relatives were at greater risk for alcohol disorders. The increased risk for anxiety disorders in the relatives of agoraphobics was not specific for agoraphobia but included panic disorder and other phobias as well. The findings indicate that agoraphobia is a familial disorder and that family data may help to determine whether agoraphobia is separate from other anxiety and phobic disorders.
A family study of panic disorder.
In a family study of panic disorder, we collected data on 278 first-degree relatives of 41 probands with panic disorder and 262 relatives of 41 control probands. The morbidity risk for panic disorder was 17.3% in the first group, and an additional 7.4% were categorized as having probable panic disorder. Both rates were significantly higher than the respective rates in the control relatives, 1.8% and 0.4%. The risk of panic disorder in female subjects was twice that in male subjects. The rate of generalized anxiety disorder was the same in both groups of families. No other psychiatric disorders were increased in the families of patients with panic disorder. In a preliminary genetic analysis, we tested the single major locus and the multifactorial polygenic transmission models. Neither model was excluded by the data. We conclude that panic disorder is a familial disease that affects women twice as frequently as men and is not associated with an increased familial risk of other psychiatric conditions. Its method of transmission remains uncertain.
Panic disorder and primary unipolar depression. A comparison of background and outcome.
Outcome at discharge and during a follow-up averaging 5 years clearly distinguished 116 panic disorder inpatients from 123 age- and sex-matched inpatient controls with primary unipolar depression - 60.2% of the primary depression patients recovered at some time during follow-up compared to only 15.5% of the panic disorder patients. Differences in recovery rates grew larger with increasing follow-up length and were undiminished by the exclusion of patients who received antidepressants or convulsive therapy. Furthermore, these two groups had no predictors of outcome in common. These findings accord with other family and follow-up studies in support of a clear separation between panic disorder and primary depression.