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Biomedical subjects

A Georgotas

Publications and source records attributed to A Georgotas.

15 recordsLinked to original sources
PubMed1989

A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients.

Fifty-one elderly depressed outpatients who had responded to antidepressants and completed continuation therapy were observed under double-blind conditions for 1 year. Twenty-three had been switched to placebo, while 13 and 15 took nortriptyline hydrochloride and phenelzine sulfate, respectively. Patients administered phenelzine did significantly better with 13.3% recurrences than patients administered either nortriptyline (53.8% recurrences) or placebo (65.2% recurrences). In addition, patients who had higher Hamilton scores and who had an earlier age of onset of the first depressive episode were significantly more likely to have recurrences.

Aged↗
PubMed1989

Plasma levels of nortriptyline and 10-hydroxynortriptyline and treatment-related electrocardiographic changes in the elderly depressed.

Thirty-one elderly depressed patients were treated for seven weeks with nortriptyline with plasma levels kept between 50-180 ng/ml. Electrocardiograms were taken at the third and seventh weeks of treatment. There were significant increases in the PR interval, QTc interval, and heart rate from before and after treatment. However, there were no consistent correlations between electrocardiographic changes during treatment and plasma levels of nortriptyline, 10-hydroxynortriptyline and either of its two isomers (E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline). Increased QRS duration after seven weeks of treatment was correlated with daily dose of nortriptyline.

Aged↗
PubMed1989

Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine.

Seventy-six elderly depressed patients who had responded to either nortriptyline or phenelzine after a trial of up to 3 months were examined. The mean week of response was nearly 6 weeks. Patients who were more severely depressed took longer to respond. Patients with endogenous depression responded sooner on nortriptyline than did patients with nonendogenous depression. For patients on nortriptyline, lower plasma levels in the early weeks of treatment may delay response while differences in platelet monoamine oxidase inhibition in the early weeks of treatment do not appear to affect week of response for patients on phenelzine.

Aged↗
PubMed1989

The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.

Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.

Affect↗
PubMed1989

10-Hydroxynortriptyline and treatment effects in elderly depressed patients.

Sixty-four elderly depressed outpatients were treated with nortriptyline for seven weeks. Plasma nortriptyline and its main metabolite, 10-hydroxynortriptyline, were measured weekly. No relationship was found between levels of 10-hydroxynortriptyline and clinical response. Plasma levels of the trans isomer, E-10-hydroxynortriptyline, were significantly lower when dizziness and symptoms of orthostatic hypotension were reported, although there was no significant correlation with actual orthostatic drop in systolic pressure. Plasma level of 10-hydroxynortriptyline was not significantly correlated with the other reported side effects.

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PubMed1987

Clinical and treatment effects on 3H-clonidine and 3H-imipramine binding in elderly depressed patients.

3H-clonidine and 3H-imipramine binding were measured in depressed patients, 55 years and older. There was no significant difference in either 3H-clonidine or 3H-imipramine binding between depressed patients and age- and sex-matched controls. There was no significant correlation between 3H-clonidine or 3H-imipramine binding and severity of depression before treatment. There was a significant negative correlation between the KD of 3H-imipramine binding sites and Hamilton score over seven weeks of antidepressant treatment. There was no significant difference between receptor data of responders and nonresponders to antidepressant treatment.

Blood Platelets↗
PubMed1979

Self-rated sedation and plasma concentrations of desmethyldiazepam following single doses of clorazepate.

Plasma concentrations of desmethyldiazepam (DMDZ) and intensity of self-rated sedation (SRS) were measured at multiple points in time during 6 h after a single 15 mg oral dose of clorazepate dipotassium. Mean plasma DMDZ levels and mean SRS scores both became maximal at 1.0--2.5 h after drug dosage. By 6 h, however, mean SRS had returned to the predrug baseline score while mean DMDZ concentration fell only slighty from the maximum value. Disappearance of SRS despite persistence of high DMDZ levels might be due to adaptation or tolerance. If this is the case, subjective effects of benzodiazepines may depend upon duration of drug exposure as well as dose and concentration.

Adult↗
PubMed1978

Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide.

Ten healthy volunteers ingested single 15-mg doses of clorazepate dipotassium (CZP) with 60 ml of water, or with 60 ml of magnesium aluminum hydroxide (Maalox), on two occasions in a randomized, two-way crossover study. Plasma concentrations of desmethyldiazepam (DMDZ) were determined in multiple samples drawn during 48 hr after each dose. Mean kinetic variables for DMDZ in CZP-water and CZP-magnesium aluminum hydroxide treatment conditions, respectively, were: peak measured concentration, 273 and 188 ng/ml (p 0.001); time of peak concentration, 1.8 and 2.8 hr after dose (p less than 0.01); apparent absorption half-life, 14.8 and 30.7 min (p less than 0.02); area under the 48-hr plasma concentration curve, 6,028 and 5,433 ng/ml X hr (p less than 0.02). Self-rated sensations of feedling "spacey," "thinking slowed down," and of generalized sedation, were reported with both treatment conditions, but these subjective effects occurred earlier and were more profound when CZP was taken with water as opposed to magnesium aluminum hydroxide. Thus administration of single doses of CZP with usual doses of a commonly prescribed antacid reduces the rate and extent of appearance in blood of DMDZ (the compound responsible for clinical activity) and attenuates self-rated clinical effects.

Adult↗
PubMedDate not supplied

Effect of abdominal radiation therapy on drug absorption in humans.

The absorption of oral digoxin and of desmethyldiazepam, from its precursor clorazepate, was studied in seven patients who had received abdominal and/or pelvic radiation therapy for neoplastic disease. All patients were in remission and had normal renal function and no evidence of malabsorption. Single 0.5-mg doses of digoxin tablets and 15-mg doses of clorazepate were administered in the fasting state. Concentrations of digoxin (by radioimmunoassay) and desmethyldiazepam (by gas chromatography) were determined in multiple plasma samples and all urine collected during 24 hours after dosage. The mean (+/- S.E.) weight-normalized area under the 24-hour plasma digoxin concentration curve (WtN-AUC-24) in the patients (722 +/- 40 ng/ml-hr-kg) was similar to that in five normal controls (713 +/- 57 ng/ml-hr-kg), but 24-hour urinary excretion of digoxin in patients (54.5 +/- 4.4 microgram) was significantly less (P less than 0.025) than in controls (83.4 +/- 11.4 microgram). Neither age, sex, nor renal function explained the difference. In the clorazepate study, WtN-AUC-24 for desmethyldiazepam in the patients (187 +/- 19 microgram/ml-hr-kg) was significantly less (P less than 0.01) than in 15 normal control subjects (230 +/- 5 microgram/ml-hr-kg). Age and sex did not explain the difference. Thus, radiation therapy, or the underlying disease, is associated with malabsorption of these two drugs, possibly because of damage to gastric acid-secreting cells.

Abdomen↗
PubMedDate not supplied

The relationship of the dexamethasone suppression test to subtypes of depression and to symptomatic severity in the elderly.

Dexamethasone Suppression Tests (DSTs) were performed on 91 subjects consisting of 66 elderly outpatients diagnosed as having major depression according to RDC and 25 age- and sex-matched healthy controls. Postdexamethasone plasma cortisol levels were significantly higher in depressed patients than in normals. The depressed patients were subdivided into endogenous and nonendogenous groups by alternately, RDC and Newcastle Diagnostic Scale (NDS). A significant difference in postdexamethasone plasma cortisol levels between endogenous and nonendogenous groups was noted only when NDS was used, but this difference was found to be related to a significant difference in severity of depression.

Aged↗
PubMedDate not supplied

The usefulness of DST in predicting response to antidepressants: a placebo-controlled study.

Seventy-two out-patients, 55 years or older, suffering from major depression were treated with either nortriptyline or phenelzine for seven weeks under placebo-controlled double-blind conditions. The dexamethasone suppression test (DST) was administered at baseline and at weeks 3 and 7 of treatment, and its usefulness in predicting and/or paralleling clinical response was examined. No correlation was found between baseline DST results and treatment response with antidepressants. Of 13 patients whose abnormal baseline DSTs normalized during treatment, six were responders and seven were nonresponders (P = 0.24). However, all (seven) patients whose DSTs persisted to be abnormal throughout the seven weeks did not respond. The authors conclude that the DST has not been shown to have practical value as an indicator of impending recovery from major depression in the elderly, but its failure to normalize may have ominous prognostic significance.

Aged↗
PubMedDate not supplied

Relapse of depressed patients after effective continuation therapy.

Forty-one elderly depressed patients who had responded to either nortriptyline or phenelzine were given continuation treatment for approximately 4 months (mean = 16.5 weeks) after which 19 were switched under double-blind conditions to placebo. At the end of 8 weeks, three (15.8%) of the placebo patients had relapsed and three (13.6%) of the patients kept on antidepressants had relapsed. Patients who had more prior episodes of depression had a greater risk of relapsing. The implications of these findings for continuation pharmacologic treatment in the elderly depressed are discussed.

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