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Biomedical subjects

J R Calabrese

Publications and source records attributed to J R Calabrese.

At least 73 records · Page 4Linked to original sources
PubMed1991

Treatment of depression. New pharmacologic approaches.

Recurrent major depression is an underdiagnosed, undertreated mood disorder that affects approximately 10 million Americans. Although the tricyclic antidepressants are the oldest and best studied class of antidepressant medications available, their use is routinely compromised by unsatisfactory pharmacokinetic and side-effect profiles. The newer antidepressant medications have longer half-lives and are less likely to produce side effects. The prototypes of the newer antidepressants are bupropion (Wellbutrin) and fluoxetine (Prozac). Fluoxetine distinguishes itself in that its half-life is 2 to 3 days, whereas the mean half-life of buproprion and the tricyclics are 10 to 14 hours. For this reason, fluoxetine is routinely administered once daily in the morning. Both of these agents bind to the cholinergic, histaminergic, and alpha-1 adrenergic receptors with minimal affinity, and are less likely to yield clinically significant side effects. The use of the newer antidepressants has led to improved patient compliance and physician acceptance.

Adult↗
PubMed1990

Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder.

In order to explore valproate's spectrum of efficacy in rapid-cycling bipolar disorder, 55 patients underwent a prospective, open, 7.8-month trial designed to assess the drug's acute and prophylactic properties. Twenty patients received monotherapy, and 35 received combination therapy. Moderate to marked acute antidepressant responses were seen in 47% of the patients, prophylactic antidepressant responses in 76%, acute antimanic responses in 91%, prophylactic antimanic responses in 94%, acute responses in mixed states in 85%, and prophylactic responses in mixed states in 93%. Consistent with other anticonvulsant literature, these data suggest that valproate has marked antimanic and mixed state efficacy, but minimal to moderate antidepressant properties.

Adult↗
PubMed1990

Buspirone augmentation of fluoxetine in obsessive-compulsive disorder.

Eleven obsessive-compulsive patients underwent a prospective open-label trial of fluoxetine monotherapy followed by buspirone augmentation. The combination therapy was statistically superior to fluoxetine monotherapy. The results point to the importance of the 5-HT1a receptor in obsessive-compulsive disorder.

Adult↗
PubMed1989

Phenomenology of rapid cycling manic depression and its treatment with valproate.

Although the recurrent nature of manic depressive illness has been recognized since the time of Kraepelin, it has only recently been noted that this feature of the illness has prognostic significance. A subgroup of patients who experience more than four major mood swings per year has been identified as rapid cyclers and are now believed to account for a significant proportion of treatment resistance. In some instances, such rapid cycling is believed to be not only exacerbated by but possibly caused by the use of conventional unimodal antidepressants such as tricyclics. For this reason, the routine use of such antidepressants should be considered ill-advised until patients have been shown to be resistant to lithium's acute antidepressant properties. Although lithium remains the initial treatment of choice for manic depression, a substantial majority of manic depressive patients prove to be lithium-resistant and a growing body of data suggests this refractory group is accompanied by a disproportionate amount of frequent mood swings. When the lithium-resistant bipolar patient is encountered, the addition of one of two anticonvulsants, either valproate or carbamazepine, often provides significant therapeutic effects. Both valproate and carbamazepine appear to be similarly effective, but valproate may be better tolerated and easier to use.

Bipolar Disorder↗
PubMed1989

Effects of glucocorticoid antagonism with RU 486 on pituitary-adrenal function in patients with major depression: time-dependent enhancement of plasma ACTH secretion.

Data from our group and others suggest that pituitary-adrenal activation in major depression reflects a defect at or above the hypothalamus which results in the hypersecretion of corticotropin-releasing hormone (CRH); some have suggested, however, that elevated indices of cortisol secretion and lack of suppressibility to dexamethasone may be a manifestation of a primary defect in glucocorticoid receptor activation. We report here a study of early morning pituitary-adrenal responses to the glucocorticoid antagonist RU 486 in patients with major depression and healthy volunteers. Previous data suggested that the response to RU 486 could represent an index of endogenous CRH secretory activity. RU 486 produced a robust increase in plasma corticotropin (ACTH) and cortisol secretion in both control subjects and depressed patients. In the controls, however, the increase was confined to the last 2 hours of sampling (6 to 8 am), whereas in the depressed patients the increase occurred throughout the sampling period (3 to 8 am). The ACTH response in the depressed patients exceeded that in the controls during most of the sampling period, including a significant (p less than .005) increase between 3 and 4:30 am. These results are compatible with the idea that hypercortisolism in major depression represents an alteration in the overall set point for hypothalamic CRH secretion rather than a primary alteration at the level of the glucocorticoid receptor.

Adrenocorticotropic Hormone↗
PubMed1988

Diagnosis of anxiety and depression.

The differential diagnosis of anxiety and depression is often difficult as symptoms of generalized anxiety, panic disorder, and depression frequently coexist.

Anxiety Disorders↗
PubMed1987

Alterations in immunocompetence during stress, bereavement, and depression: focus on neuroendocrine regulation.

There is now clear evidence that stress, bereavement, and depression can compromise specific components of the immunologic apparatus. The first part of this paper gives an overview of fundamental immunology and is followed by a review of the patterns, possible causes, and potential clinical implications of abnormal immunoregulation. After a discussion of the immunomodulating properties of glucocorticoids, the authors conclude with an overview of the many factors that mediate the complex interdependence between immunologic function, the brain, and neuroendocrine regulation.

Brain↗
PubMed1987

Corticotropin releasing hormone: relevance to normal physiology and to the pathophysiology and differential diagnosis of hypercortisolism and adrenal insufficiency.

CRH is a 41 amino acid peptide first isolated from ovine and subsequently from rat and human hypothalami. We have conducted a series of clinical studies with oCRH and hCRH in volunteers and patients with various disorders of hypothalamic-pituitary-adrenal function. In volunteers, it was demonstrated that hCRH administration produced ACTH and cortisol responses which closely mimic naturalistically occurring secretory episodes. This data, as well as the demonstration that pulsatile hCRH can reestablish normal ACTH and cortisol secretion in patients with hypothalamic CRH deficiency, strongly argue that CRH is of physiological relevance to the human pituitary-adrenal axis. However, since the ACTH response to an insulin tolerance test is greater than the maximal ACTH response to CRH, other factors such as vasopressin may be relevant to stress-induced ACTH secretion in man. Following the demonstration that CRH seems to be of physiological relevance to human subjects, a CRH stimulation test was developed based on pharmacokinetic and dose response studies with oCRH and hCRH. Based on these data, which revealed that oCRH functions as a long-acting analogue of hCRH, and the demonstration that hormonal responses to CRH are greatest in the evening, patient groups with abnormalities of the hypothalamic-pituitary-adrenal axis were tested with intravenous oCRH with a dose of 1 micrograms/kg given at 2000 hours. This CRH stimulation test has proved helpful in clarifying the pathophysiology of hypercortisolism in a variety of psychiatric disorders characterized by this endocrine abnormality. Thus, blunted ACTH responses in hypercortisolemic patients with depression, anorexia nervosa, and panic anxiety disorder indicate normality of the pituitary corticotroph in these patient subgroups. These data, along with the finding that a continuous infusion of CRH to normal volunteers, reproduces the pattern and magnitude of hypercortisolism in depression and anorexia nervosa, suggest that the hypercortisolism in these disorders represents a defect at or above the hypothalamus resulting in the hypersecretion of CRH. This hypothesis is particularly intriguing in light of the demonstration that CRH administration to experimental animals produces many of the physiological and behavioral responses classically associated with depression and anorexia nervosa, including hypercortisolism, hypothalamic hypogonadism, and decreases in libido and appetite. The CRH stimulation test has also helped to resolve one of the oldest endocrinological dilemmas, namely whether the hypercortisolism of depression and Cushing's disease share a common or dissimilar pathophysiological basis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Insufficiency↗
PubMed1986

Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. Pathophysiologic and diagnostic implications.

Primary depression can be associated with substantial hypercortisolism, thus prompting some researchers to suggest that depression shares pathophysiologic features with Cushing's disease. Clinically, depression can be difficult or impossible to distinguish from mild or early Cushing's disease that is associated with depressive features. The purpose of this study was to evaluate whether the pituitary-adrenal responses to ovine corticotropin-releasing hormone could help to clarify the mechanism of hypercortisolism in depression and in Cushing's disease and to assist in the differential diagnosis of these disorders. As compared with controls (n = 34), depressed patients (n = 30) had basal hypercortisolism (P less than 0.001) that was associated with attenuated plasma ACTH responses to ovine corticotropin-releasing hormone (P less than 0.001). This indicates that in patients with depression, the corticotroph cell in the pituitary responds appropriately to the negative feedback of high cortisol levels. In contrast, patients with Cushing's disease (n = 29) had plasma ACTH hyperresponsiveness to ovine corticotropin-releasing hormone (P less than 0.001), despite basal hypercortisolism (P less than 0.001), which indicates a gross impairment of the mechanism by which cortisol exerts negative feedback on the pituitary. Less than 25 percent of the patients with depression or Cushing's disease had peak ACTH responses that overlapped. We conclude that the pathophysiologic features of hypercortisolism in depression and Cushing's disease are distinct in each of the disorders and that the ovine corticotropin-releasing hormone stimulation test can be helpful in their differential diagnosis.

Adrenocorticotropic Hormone↗
PubMed1986

Depression, immunocompetence, and prostaglandins of the E series.

Plasma prostaglandin E1 and E2, and quantitative and qualitative measures of immune function, were determined in depressed patients and healthy controls. Prostaglandin E2 was significantly elevated in the depressed group, and prostaglandin E1 showed a trend in the same direction. Lymphocyte stimulation responses, as measured by phytohemagglutinin, concanavalin A, and pokeweed mitogen, were significantly lower in the depressed group. Helper and suppressor T cell percentages did not significantly differ in the two populations. In the depressed group, prostaglandin E1 showed a significant inverse correlation with concanavalin A, and prostaglandin E2 showed a similar trend. These preliminary data suggest prostaglandins of the E series may be related to abnormalities of cellular immunity previously documented in depression.

Alprostadil↗
PubMed1986

Abnormal ACTH and cortisol responses to ovine corticotropin releasing factor in patients with primary affective disorder.

To further explore hypothalamic pituitary adrenal regulation in patients with affective illness, we administered 1 microgram/kg of synthetic ovine corticotropin releasing factor at 2000h to 26 drug-free patients with this disorder and to 15 healthy controls. Compared to controls, depressed patients (N = 12) showed a significant elevation in baseline cortisol and significant reductions in the net ACTH and cortisol responses to corticotropin releasing factor. These findings were normal in manic (N = 6) and improved (N = 8) subjects. An additional finding was that baseline cortisol and net ACTH and cortisol responses to CRF were negatively correlated in the entire group of patients and controls as well as in the patients alone. These data indicate that the reduced ACTH and cortisol responses to CRF in depression reflect normal functioning of the pituitary corticotroph cell (i.e., that the negative feedback effect of cortisol on ACTH secretion in depression is physiologically intact, effectively serving as a brake on the ACTH response to exogenous CRF. Thus, the hypercortisolism of depression may be due to a hypothalamic defect, possibly involving hypersecretion of endogenous CRF. This possibility may be of particular interest in light of clinical observations that depression can often be precipitated by stress and by data in experimental animals that CRF may influence several processes known to be altered in the overall symptom complex of depression.

Adrenocorticotropic Hormone↗
PubMed1985

Corticotropin releasing factor: basic studies and clinical applications.

Corticotropin releasing factor (CRF) is a newly sequenced peptide first isolated from sheep hypothalami and thought to be an important modulator of both the pituitary-adrenal axis and the sympathetic nervous system. We administered intravenous, intramuscular, and intracerebroventricular CRH to non-human primates and measured plasma ACTH, beta endorphin, cortisol, GH and PRL responses to CRF. In addition, we determined the pharmacokinetic properties of I125 in these primates. We administered CRF as an intravenous bolus or as a continuous infusion to normal volunteers and as an intravenous bolus to patients with disorders of the hypothalamic-pituitary-adrenal axis, such as Cushing's syndrome and adrenal insufficiency, and patients with endogenous depression and mild hypercortisolism, and assessed their plasma ACTH, cortisol, GH and PRL responses. In addition, we determined the pharmacokinetic properties of CRF in man by measuring CRF immunoreactivity in plasma. CRF given intravenously to primates or man is a slowly metabolized, long-acting, secretagogue of ACTH, beta-endorphin and cortisol. When given intracerebroventricularly to primates it stimulates the hypothalamic-pituitary-adrenal axis without escaping into the plasma and it is actively cleared in the CNS. It does not cross the blood brain barrier appreciably when given intravenously. CRF given to primates and men as an intravenous continuous infusion has only mild ACTH stimulating effects and this may be due to an intact cortisol negative feedback system. Finally, CRF causes characteristic plasma hormone responses in patients with Cushing's disease, adrenal insufficiency and depression.

Adrenal Insufficiency↗