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Biomedical subjects

T B Cooper

Publications and source records attributed to T B Cooper.

At least 163 records · Page 9Linked to original sources
PubMed1988

Tyramine sulfate excretion may be a better predictor of antidepressant response than monoamine oxidase activity.

The tyramine sulfate excretion test was performed on 62 nonmelancholic depressed outpatients who then took part in a 6-week double-blind trial comparing imipramine, phenelzine, and placebo. In a double-blind design, nonresponders were switched to one of the active medications. Tyramine sulfate excretion failed to differentiate response from nonresponse to placebo. By contrast, phenelzine responders excreted significantly less tyramine sulfate than did phenelzine nonresponders, while there was a trend in the same direction for imipramine-treated patients. The presence of only eight phenelzine nonresponders dictates caution in interpreting these results. Baseline monoamine oxidase (MAO) activity did not distinguish responders from nonresponders or correlate with tyramine sulfate excretion. Although males had significantly lower MAO activity than females, controlling for sex did not alter these negative findings. These results fail to confirm a previous report of a significant correlation between MAO activity and treatment response in older, mainly melancholic patients.

Adult↗
PubMed1988

Electrocardiographic changes with nortriptyline and 10-hydroxynortriptyline in elderly depressed outpatients.

Pharmacokinetic factors may contribute to altered nortriptyline effects in the elderly. Plasma concentrations of nortriptyline's principal metabolite, E-10-hydroxynortriptyline, tend to be greater than nortriptyline, increase with age, and may contribute to cardiotoxicity. Electrocardiogram changes were evaluated in 21 ambulatory, elderly, depressed outpatients who were treated with therapeutic doses of nortriptyline. Resting electrocardiograms were obtained before and after 6 weeks of treatment. Plasma samples were assayed simultaneously for nortriptyline, E-, and Z-10-hydroxynortriptyline. Three subjects developed a first degree atrioventricular block and one developed a right bundle branch block during treatment. Mean daily nortriptyline dose and steady state plasma level in these subjects did not differ from those who did not develop conduction defects, but E-10-hydroxynortriptyline levels were significantly higher. Overall, there were significant correlations between changes in the PR interval and QRS duration with plasma concentrations of nortriptyline, E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline, and the sum of nortriptyline and its 10-hydroxynortriptyline metabolites. Multiple regression analyses suggested that increases in PR interval were associated with increasing nortriptyline concentration, while increases in QRS duration and Q-Tc intervals were associated with increasing Z-10-hydroxynortriptyline concentration. E- and Z-10-hydroxynortriptyline may contribute substantially to the cardiac conduction effects of nortriptyline treatment and may be of particular importance in the elderly.

Aged↗
PubMed1988

Antidepressants in the treatment of post-psychotic depression in schizophrenia: drug interactions and other considerations.

Adjunctive imipramine has been found to be useful in the treatment of a substantial number of patients with syndromally defined post-psychotic depressions. This paper examines the clinical effects of the combined anticholinergic activity of imipramine, when added to ongoing fluphenazine decanoate/benztropine treatment, in such patients. Little additional anticholinergic impact of the imipramine was observable beyond that already attributable to the benztropine, and no significant relationships were found between a clinical measure of peripheral anticholinergic activity and either global clinical outcome or antidepressive efficacy. This paper also reports on the concentrations of imipramine and its metabolites in plasma under the conditions of this therapeutic trial. The changes in relative concentrations of imipramine and metabolites with time were consistent with the concept that fluphenazine competes with tricyclic metabolism. The relationship of plasma imipramine and desipramine to clinical improvement in this group of secondary depressions did not parallel previously reported relationships of these antidepressant molecules to clinical outcome in primary depressions.

Adult↗
PubMed1988

Patterns of plasma imipramine-desipramine concentrations in patients receiving concomitant fluphenazine decanoate.

Plasma levels of imipramine and desipramine were monitored in a series of 13 patients with postpsychotic depressions who had a fixed dose of imipramine (150 mg/day) added to their clinically adjusted, stable dose of fluphenazine decanoate. Despite the potential for metabolic inhibition of the tricyclic drug by the neuroleptic drug, no relationship was found between the fluphenazine dose and the subsequent plasma concentrations of imipramine and desipramine. However, plasma antidepressant levels after 1 week at a low dose (50 mg/day) identified patients who later generated high plasma antidepressant levels at the full antidepressant dosage. The clinical implications of these observations are discussed.

Adult↗
PubMed1987

Correlation of type A behaviour with adrenergic receptor density: implications for coronary artery disease pathogenesis.

In 17 healthy young men who had a parent with documented early coronary disease, ratings of type A behaviour correlated with upregulated lymphocyte beta 2 receptor density and inversely with the ratio of platelet alpha 2 to lymphocyte beta 2 receptor density ratio. This indicates a correlation of type A behaviour with receptor-based determinations of increased peripheral alpha-adrenergic balance, consistent with increased coronary arterial vasoconstriction, perhaps leading to coronary artery disease.

Adult↗
PubMed1987

Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial.

The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine.

Adult↗
PubMed1987

Concurrent lithium administration results in higher haloperidol levels in brain and plasma of guinea pigs.

The effects of lithium (Li) on brain and plasma levels of concurrently administered haloperidol (HAL) were investigated. One group of guinea pigs (n = 12) was also treated with HAL for 11 days, but Li was added during the last 5 days of treatment. At the end of treatment, the HAL + Li group had significantly higher brain and plasma levels of HAL than the group treated with HAL alone. The correlation coefficient between plasma and brain HAL (0.97) indicated that plasma levels of HAL determine brain levels of this drug.

Animals↗
PubMed1987

Cardiovascular effects of doxepin in cardiac patients with ventricular arrhythmias.

The effect of doxepin on ventricular arrhythmias, the ECG, and left ventricular function was evaluated in 10 cardiac patients with symptoms with frequent ventricular premature depolarizations in a dose-ranging protocol. Four patients (40%) had greater than or equal to 80% ventricular premature depolarization suppression; four of eight with pairs and four of six with ventricular tachycardia had greater than or equal to 90% suppression. The mean maximal doxepin dose was 115 +/- 41 mg/day; mean nadir total doxepin concentration was 61 +/- 48 ng/ml and mean nadir total desmethyldoxepin concentration was 51 +/- 42 ng/ml. Doxepin increased the heart rate and the PR, QRS, and QTc intervals of the surface ECG (P not significant). There was no significant change in resting mean left ventricular ejection fraction with doxepin: 41% +/- 15% vs. 43% +/- 19% (P not significant). Complaints of sedation (eight patients) limited dose ranging and tolerance to the drug. Although doxepin suppressed ventricular premature depolarizations in four patients, marked sedation limits its usefulness for primary treatment of arrhythmias in this population.

Adult↗
PubMed1987

Plasma-serum differences in the assessment of tricyclic antidepressant blood levels.

Concomitant plasma and serum tricyclic determinations were performed on 20 patients chronically administered imipramine (N = 10), amitriptyline (N = 10), desipramine (N = 10), and nortriptyline (N = 10). Plasma levels for these tricyclic antidepressants were significantly greater than the corresponding serum levels. Plasma-serum differences for the secondary amines (DMI/NT) were more than twice those for the tertiary amines (IMI/AMI). The authors thus suggest that clinicians and investigators specify the specific source of blood sample when assessing blood levels of the secondary tricyclic antidepressants.

Amitriptyline↗
PubMed1987

Electrocardiographic effects of nortriptyline, phenelzine, and placebo under optimal treatment conditions.

The authors treated 44 outpatients 55 years old or older who were suffering from major depression with either nortriptyline, phenelzine, or placebo for 7 weeks. Plasma levels of nortriptyline were kept between 50 and 170 ng/ml, and platelet monoamine oxidase (MAO) inhibition in phenelzine-treated patients was kept between 70% and 80%. ECGs were compared before and after treatment. Nortriptyline produced statistically significant increases in both the heart rate and the PR interval, although none was outside the normal range. Phenelzine produced a significant decrease in the QT interval. None of the patients had pathological ECG changes under the closely monitored treatment conditions of this study.

Aged↗
PubMed1987

Response of depressive symptoms to nortriptyline, phenelzine and placebo.

The effects of nortriptyline, phenelzine, and placebo on 13 symptoms of depression were compared in 75 patients, aged 55 or over, who were suffering from major depression. Nortriptyline and phenelzine were more effective than placebo in treating depression mood, guilt feelings, suicidal ideation, agitation, anxiety, loss of energy, and a.m. diurnal variation of mood. Nortriptyline was better than phenelzine or placebo in improving middle/late insomnia. Most of the symptoms did not show significant improvement until the fourth week of treatment.

Aged↗