Biomedical subjects

A J Fyer

Publications and source records attributed to A J Fyer.

At least 73 records · Page 4Linked to original sources

PubMed1989

A neuroanatomical hypothesis for panic disorder.

Anxiety disorders, the most common psychiatric conditions in the United States, have generated a great deal of research and scientific debate. Panic disorder, the best-studied anxiety disorder, is often believed to be either a biological disease or a psychological disease. The authors present a neuroanatomical model of panic disorder that attempts to reconcile these views. The model locates the three components of the disease--the acute panic attack, anticipatory anxiety, and phobic avoidance--in three specific sites of the CNS: the brainstem, limbic system, and prefrontal cortex, respectively. The authors suggest experiments to test their model.

Acute Disease↗

PubMed1989

Hypersensitivity to carbon dioxide in panic disorder.

Seven male panic patients did not panic but were significantly more sensitive to steady-state carbon dioxide inhalation than five male normal control subjects. The male patients' hypersensitivity to carbon dioxide was unrelated to current state of anxiety or acute panic.

Anxiety↗

PubMed1988

Ventilatory physiology of patients with panic disorder.

Thirty-one patients with DSM-III panic disorder or agoraphobia with panic attacks, 13 normal controls, and 12 patients with other anxiety disorders were studied during ventilatory challenge with room air hyperventilation and 5% carbon dioxide inhalation. Patients also underwent sodium lactate infusion. Among the patients with panic disorder, 58% panicked with sodium lactate, 39% with 5% CO2, and 23% with room air hyperventilation. Of the other patients, four panicked with sodium lactate, none with 5% CO2, and one with room air hyperventilation. One normal control panicked with both sodium lactate and 5% CO2. Panic with CO2 was associated with an exaggerated ventilatory response and increases in plasma norepinephrine level and diastolic blood pressure. Patients with panic disorder may have hypersensitive CO2 receptors that, when triggered, evoke a subjective panic associated with an exaggerated ventilatory response and consequent hypocapnic alkalosis.

Adult↗

PubMed1988

Tricyclic therapy of the DSM-III anxiety disorders: a review with implications for further research.

Existing data suggests dramatic efficacy for all tested tricyclics in disorders involving spontaneous panic attacks; moderate efficacy for clomipramine but not other tricyclics in obsessive-compulsive patients; possible, but as yet not well established, tricyclic efficacy in generalized anxiety; and lack of efficacy in simple phobias. Further studies in all DSM-III Anxiety Disorders are both warranted and required to answer the nosological, pathophysiological and treatment questions raised by these findings.

Adolescent↗

PubMed1988

Epinephrine infusions in patients with social phobia.

To assess the role of peripheral epinephrine in social anxiety, the authors infused 11 patients meeting DSM-III criteria for social phobia with intravenous epinephrine over 60 minutes. Although the mean plasma epinephrine level increased from 113 to 928 pg/ml, only one of the 11 patients experienced observable anxiety; this finding suggests that an increase in plasma epinephrine level alone is inadequate to cause social anxiety. Of the variables measured, only the average minute volume correlated with self-rated anxiety. Ventilatory indexes might be better correlates of subjective anxiety than other physiological variables.

Adult↗

PubMed1988

Effects of clonidine on alprazolam discontinuation in panic patients: a pilot study.

Effects of adjunctive clonidine (0.15 to 0.7 mg/day) on symptoms experienced during and for 4 weeks after gradual alprazolam discontinuation were observed in panic disorder patients after 6 weeks of successful treatment. Twelve of 14 entered patients were considered to have had a sufficient period of discontinuation (2 weeks) and clonidine administration (1 week) for effects to be assessed adequately. Nine of these 12 patients reached zero dose of alprazolam in 3 to 4 weeks. However, 10 of 12 patients experienced new withdrawal symptoms and 11 of 12 experienced recurrent panic attacks during tapering. Although a greater proportion of patients were successfully discontinued in a shorter time than in a previous nonclonidine trial, clonidine did not appear to have a specific effect on relapse or withdrawal. A placebo-controlled trial is needed to discriminate between possible contributions of clonidine and other factors (e.g., physician attitude, placebo effect of pill taking) to this improved outcome.

Adult↗

PubMed1988

Pharmacotherapy of social phobia: an interim report of a placebo-controlled comparison of phenelzine and atenolol.

Forty-one patients meeting DSM-III criteria for social phobia completed a randomized comparative trial of the monoamine oxidase inhibitor phenelzine, the cardioselective beta-adrenergic blocker atenolol, and placebo. No significant differences were seen after 4 weeks of treatment in this preliminary trial. At the end of 8 weeks, however, phenelzine demonstrated greater efficacy than atenolol or placebo on dimensional ratings of overall severity of social phobia. No atenolol-placebo differences were observed. The authors shall present maintenance and discontinuation findings in a final report. Phenelzine may act in patients with social phobia by directly reducing interpersonal hypersensitivity.

Adult↗

PubMed1987

Measurement of lactate-induced panic and anxiety.

Acute Panic Inventory (API) scores were obtained from 26 normal controls and 89 patients with either panic disorder or agoraphobia with panic attacks before and during lactate infusions. Retrospective ratings of the patients' usual spontaneous attacks were much higher, by API, than ratings of moments of severe stress by the controls. Point of panic API scores, as well as increments of panic scores over prelactate scores, were higher for patients who experienced lactate panics than for both controls and patients who did not panic.

Adult↗

PubMed1987

Antipanic drug effects during lactate infusion in lactate-refractory panic patients.

In previous articles we have reported on the total Acute Panic Inventory (API) score during lactate-induced panic. Even patients with panic disorder who do not panic during lactate infusion have higher API scores during the infusion than normal controls. In this post hoc analysis, we wished to determine whether specific API items were more sensitive to the beneficial effects of antipanic medication, either at baseline or during the infusion, in these lactate-insensitive panic patients. Four of the 17 items showed specific drug blockade of baseline severity. Five additional items showed specific drug blockade of lactate exacerbation of symptom severity. Medication apparently had no effect on severity of the remaining eight items. We suggest that the nine symptoms that responded to drug therapy are associated with hyperventilation. The study indicates that antipanic drugs may have a specific effect in blunting hyperventilation.

Adult↗

PubMed1987

Pituitary adrenocortical unresponsiveness in lactate-induced panic.

The hypothalamic-pituitary adrenal (HPA) axis responds to a variety of physical and emotional stimuli with increased output of adrenocorticotropic hormone (ACTH) and cortisol, yet there is little known about the activity of this system during episodes of severe anxiety in patients with DSM-III-defined anxiety disorders. To explore further whether alterations of the HPA axis occur during various anxiety states, we measured ACTH and cortisol during lactate infusion in patients with panic disorder and agoraphobia. In eight patients who panicked during lactate infusion, there were no elevations in either ACTH or cortisol. Further, the patterns of hormone secretion did not differ among patients who panicked, nonpanicking patients, or controls. This negative result suggests that the neurobiological mechanisms that mediate panic differ from those responsible for other fear responses.

Adolescent↗

PubMed1987

An objective marker of lactate-induced panic.

There are a number of agents claimed effective in provoking panic attacks in the laboratory. For each case, however, the determination of whether an attack has occurred is largely subjective. An objective index of panic would be of great benefit in standardizing laboratory provocation studies. Using heart rate (HR) recordings during sodium lactate infusion, we developed a formula--the heart rate index (HRI)--which appears to correlate well with the subjective experience of panic. Of note is the fact that the HRI was most powerful in identifying attacks that occurred in the first 15 min of the 20-min infusions. In an accompanying study, we examined HR variability during the infusions using the successive difference mean square statistic. HR variability did not change during lactate-induced panic attacks. Therefore, tachycardia during lactate-induced panic probably does not result from decreased vagal tone to the heart.

Adult↗

PubMed1987

Agoraphobia.

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Agoraphobia↗

PubMed1987

Simple phobia.

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Arousal↗

PubMed1987

Discontinuation of alprazolam treatment in panic patients.

Alprazolam treatment was tapered in 17 panic patients at a rate of 10% of the starting dose every 3 days. Only four subjects completed withdrawal on schedule (4-5 weeks); four additional subjects discontinued treatment in 7-13 weeks. During withdrawal 15 patients had recurrent or increased panic attacks and nine had significant new withdrawal symptoms. Most common among the latter were malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness. None had seizures, psychosis, or significant neurological or EEG abnormalities. Results indicate that relapse and withdrawal are important considerations in the choice of alprazolam treatment for panic attacks.

Acute Disease↗

PubMed1987

An open trial of fluoxetine in the treatment of panic attacks.

Fluoxetine is a new antidepressant with pharmacologic effects apparently limited to blockade of neuronal serotonin reuptake. We entered 20 patients who met DSM-III criteria for either panic disorder or agoraphobia with panic attacks into an open, uncontrolled pilot study of fluoxetine. Four responded to placebo in the week before fluoxetine administration and were dropped from the study. Of the remaining 16 patients, nine were nonresponders and seven were responders, with complete cessation of their panic attacks. Eight of the nine nonresponders were unable to tolerate the side effects of fluoxetine. In contrast, all of the responders (and one nonresponder) experienced minimal side effects. Fluoxetine may be effective in the treatment of panic attacks, perhaps implicating the serotonergic system in the pathophysiology of panic disorder. Future studies should use very low doses of fluoxetine to initiate treatment.

Adult↗

PubMed1986

Blood gas changes and hypophosphatemia in lactate-induced panic.

Alkalosis is prominent among the many physiologic and biochemical effects of sodium lactate infusion. Though this is partially due to the conversion of lactate to bicarbonate, the metabolic component, it may also be secondary to hyperventilation before and during the infusion, the respiratory component. We analyzed pH, carbon dioxide pressure, bicarbonate, and inorganic phosphate from patients with panic disorder and agoraphobia with panic attacks and from normal controls both before and during lactate infusion. Our findings extend earlier work demonstrating that many such patients are chronic hyperventilators. Both metabolic and respiratory alkalosis develop in all subjects during lactate infusion, but only hyperventilation-induced hypocapnia differentiates patients at the point of lactate-induced panic from nonpanicking patients and normal controls. Finally, low inorganic phosphate levels at baseline appear associated with patients who will panic during the subsequent lactate infusion. This last unexpected finding may reflect hyperventilation or an abnormality in intracellular glycolysis.

Adult↗

PubMed1986

Schedule for Affective Disorders and Schizophrenia--Lifetime Version modified for the study of anxiety disorders (SADS-LA): rationale and conceptual development.

The SADS-LA, a modification of the Lifetime Version of the Schedule for Affective Disorders and Schizophrenia, was designed specifically for studies requiring detailed lifetime information on anxiety disorders, symptoms and traits. This article focuses on current difficulties in assessing and conceptualizing anxiety disorders, as addressed in the SADS-LA. The following topics are discussed: conceptual differentiation of certain anxiety disorders; sub-threshold symptoms and syndromes; the relationship between affective and anxiety syndromes; the residual category, Generalized Anxiety Disorder. We emphasize a lifetime sequential approach to diagnostic assessment for a comprehensive understanding of the interrelationships between mental disorders.

Agoraphobia↗

PubMed1986

Alprazolam in the treatment of panic disorders.

An open clinical trial of alprazolam therapy of patients with panic disorder or agoraphobia with panic attacks was undertaken to clarify certain issues not resolved by previous studies. These included the proportion of patients who significantly improve with alprazolam; the relative time courses for improvement in panic attacks, anticipatory anxiety, and phobic avoidance; whether successful alprazolam treatment alters vulnerability to panic with sodium lactate infusion; and what factors predict response to alprazolam in panic patients. Thirty patients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks completed a 12-week open clinical trial, and 22 were considered responders. In responders, panic attacks showed rapid improvement, whereas improvement of anticipatory anxiety and phobic avoidance was more variable. Successful alprazolam therapy appeared to block lactate vulnerability. High pretreatment Hamilton Anxiety Scale scores were associated with poor treatment response. The data suggest that alprazolam is an effective treatment for panic disorder and agoraphobia with panic attacks, and acts by directly blocking panic attacks.

Adult↗