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Biomedical subjects

A Georgotas

Publications and source records attributed to A Georgotas.

At least 37 records · Page 2Linked to original sources

First results on the effects of MAO inhibition on cognitive functioning in elderly depressed patients.

Elderly depressed patients who met the Research Diagnostic Criteria (RDC) for major depressive illness, were treated with phenelzine, a non-selective monoamine oxidase inhibitor, for a period of 2 to 7 wk, following 2 wk of placebo washout period. Possible pre- and post-treatment differences on the cognitive test battery were evaluated using the Wilcoxon test. Although recovery from depression was obtained in the majority of patients (Hamilton, Global and Self-rating Scales), none of the cognitive measures showed statistically significant changes over the course of the treatment period and the cognitive tests scores did not change as a result of treatment. It is of interest that tricyclic antidepressants (TCAs) are known to impair memory in geriatric patients, presumably due to their sedative and anticholinergic effects. The lack of an adverse cognitive effect for phenelzine therefore suggests a possible advantage of monoamine oxidase inhibitors over tricyclic antidepressants for the treatment of geriatric depression.

Aged↗

Affective disorders in the elderly: diagnostic and research considerations.

Although depressive disorders in the elderly represent a major public health concern by virtue of their high cost in human suffering, disability, and potential suicide, they have not been studied extensively, and specific criteria for diagnostic classification and optimal treatment are lacking. It seems likely that many of the affective syndromes in the elderly like senile melancholia, manic depressive illness, pseudodementia, and masked depression belong to the group of endogenous depressions, and can be identified by a constellation of clinical symptoms (endogenous or endogenomorphic profile), abnormal dexamethasone suppression test (DST) (at least 50%), and positive response to treatment with antidepressant medication. The rest are depressions reactive to psychogenic or sociogenic factors frequently presenting agitation as a dominant symptom, and finally there is a group of organic depressions due to underlying organic brain change, (i.e. senile dementia). It is possible that careful psychometric and psychiatric evaluation based on the symptom pattern, DST, and response to treatment would reveal reliable differences between pseudodementia and mild dementia and distinguish endogenomorphic from non-endogenomorphic depressions, respectively. The validity of such an approach remains to be demonstrated. Biological research in this area has provided valuable findings and should be the aim for the 1980s.

Aged↗

Resistant geriatric depressions and therapeutic response to monoamine oxidase inhibitors.

Elderly depressed patients who met the research diagnostic criteria (RDC) for major depressive illness, resistant to other types of treatment, were treated with phenelzine, a nonselective monoamine oxidase (MAO) inhibitor, for a period of 2 to 7 weeks, following 2 weeks of placebo washout period. Dosage ranged from 15-75 mg daily. Clinical status of patients as well as vital signs, EKG, and platelet MAO inhibition were measured weekly. All responders at the end of this period were followed for 1 to 2 years. Analysis of the results showed a 65% response rate as measured by Hamilton, Global, and Self-rating Scales. No significant drug effect in cognitive functioning, as measured by objective cognitive tests, was observed. Clinical improvement was sustained for all participants throughout the follow-up period with no side effects. A direct relationship between platelet MAO inhibition and clinical response was found. The majority of the responders (70%) had achieved high platelet MAO inhibition values (greater than 80%), while most of the nonresponders had platelet MAO inhibition values of less than 80%. These findings have potential clinical and research implications for treating geriatric depression, especially the ones resistant to other forms of treatment.

Aged↗

A double-blind comparison of trebenzomine and thioridazine in the treatment of schizophrenia.

Forty inpatient volunteers with diagnoses of schizophrenia were randomly assigned to treatment either with trebenzomine or thioridazine in a double-blind study of clinical antipsychotic efficacy following a 1-week placebo treatment. Psychopathology was rated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). There was a significant difference in therapeutic response to the two drugs in that psychopathology decreased significantly for the thioridazine group, but not for the trebenzomine group. Serum prolactin was elevated during treatment with thioridazine, but not with trebenzomine. Side effects were more frequently reported for the thioridazine group. These results fail to confirm previous reports of clinical antipsychotic efficacy for trebenzomine.

Adolescent↗

Effect of age and sex on disposition of desmethyldiazepam formed from its precursor clorazepate.

Desmethyldiazepam (DMDZ) disposition was evaluated in 32 healthy male and female volunteers who ingested single 15-mg doses of the precursor compound, clorazepate dipotassium. DMDZ concentrations were measured in multiple plasma samples obtained between 7 and 9 days after dosage. Appearance of DMDZ in blood was rapid, with peak concentrations attained on average 1.5 h after dosage. Absorption half-life (t1/2 a) averaged 24 min. Neither peak time nor t1/2 a were influenced by age or sex. After a rapid phase of distribution, DMDZ elimination was slow, with a mean elimination half-life (t1/2 beta) of 82 h (range 27-219 h). t1/2 beta became prolonged with age in men but not in women. Likewise, clearance of total (free bound) DMDZ declined with age in male subjects (r=- 0.47, P less than 0.1), but was unrelated to age in women. DMDZ was extensively bound to protein in all subjects. The mean free fraction (FF) was 3.1% (range 2.0-4.3%), and increased significantly with declining plasma albumin concentrations (r=-0.57, P less than 0.001). Partly due to a decline in plasma albumin with age (r=-0.47, P less than 0.01), FF tended to increase with age (r=0.23). After correction for individual differences in FF, clearance of pharmacologically active unbound DMDZ declined significantly with age in men (r=-0.65, P less than 0.01), but actually was slightly higher in elderly as opposed to young women. Thus, the age-related decline in the capacity for hepatic hydroxylation of DMDZ is highly sex-specific.

Adult↗

Monoamine oxidase activity and enzyme kinetics in three subpopulations of density-fractionated platelets in chronic paranoid schizophrenics.

Platelet monoamine oxidase (MAO) activity was studied in three subpopulations of density-fractionated platelets in 15 unmedicated chronic paranoid schizophrenic patients and contrasted with normal controls. No significant difference in MAO activity was found in any of the three platelet fractions in schizophrenics compared to controls. Enzyme kinetic studies performed on the intermediate-density platelet fraction demonstrated no significant differences in Vmax or Michaelis' constant (Km) between schizophrenics and controls, but showed that the higher platelet MAO activity reported in females compared to male is due to a significantly greater Vmax rather than altered Km. It is suggested that conflicting results reported in the literature regarding platelet MAO in schizophrenia are not related to the platelet subpopulations studied but are largely due to the selected patient populations.

Adult↗

Historical perspectives and current highlights on lithium treatment in manic-depressive illness.

This article reviews the use of lithium from Roman times, when physicians first recommended alkaline springs in the treatment of mania, to the present. Serious interest in lithium began in 1949, with a report of improvement of mania in 10 of 10 patients. Since then, lithium has become increasingly popular both for treating acute mania and as a prophylactic agent. Its use in depression is also described. Finally, lithium's clinical spectrum is discussed, noting that its use extends far beyond the treatment of mania.

Bipolar Disorder↗

A controlled study of trazodone, imipramine, and placebo in outpatients with endogenous depression.

A 4-wk double-blind controlled study of the antidepressant efficacy of the triazolopyridine derivative trazodone, in contrast to imipramine and placebo, was carried out in 30 endogenously depressed outpatients. Trazodone was found to be equivalent in efficacy to imipramine and statistically significantly superior to placebo. Trazodone showed a significant antidepressant effect relative to placebo when outcome was measured after only 7 days of treatment. This antidepressant effect was sustained for at least 5 mo as indicated by an open study phase following the double-bind study. Side effects, particularly anticholinergic properties, were significantly less apparent on trazodone compared to imipramine. A limited study of the relationship of trazodone plasma levels to therapeutic outcome revealed no simple linear relationship and represents a direction for future research.

Adult↗

Safety data on zimelidine hydrochloride following an overdose.

Zimelidine, a new antidepressant, has proved to be a potent and selective inhibitor of 5-HT uptake into central 5-HT neurons. Due to its structural differences from the tricyclic antidepressants, it has also been suggested that it may have a different pharmacological profile, and be devoid of anticholinergic and noradrenaline potentiating properties. During the treatment with zimelidine hydrochloride, as a part of an open trial, one of our patients, a 38-year-old chronically depressed woman, overdosed herself with more than 10 times the actual therapeutic dose of zimelidine with no undesirable side effects. Previous studies have indicated that zimelidine in comparison with imipramine and chlorimipramine has no, or at most, a slight effect on peripheral adrenergic neurons, and has less pronounced anticholinergic properties than imipramine. The findings of our overdose case provide some support for these findings.

Adult↗

The importance of dietary control in metabolic studies of manic-depressive patients.

Diet control of electrolyte intake appears to diminish day to day variation of urinary electrolyte output. Urine sodium concentration is more affected by diet control than potassium, possibly due to the greater variation in sodium ingestion on uncontrolled diets. The coefficient of variation of urinary sodium excretion on the controlled diet was not significantly greater than the variation in sodium ingestion. These experimental results suggest that controlled diets reduce random variation in sodium and potassium excretion and therefore enhance the possibility of observing illness-related biological changes.

Bipolar Disorder↗