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Biomedical subjects

W H Coryell

Publications and source records attributed to W H Coryell.

25 records · Page 2Linked to original sources

Doxepin kinetics.

The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first-order kinetics. The mean DOX half life (t1/2) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first-pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean t1/2 of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t1/2s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady-state concentrations of DOX and DMD in patients given DOX.

Adult↗

Protriptyline kinetics.

The kinetics of protriptyline were examined in 8 subjects after a single oral dose of 30 mg protriptyline hydrochloride. Peak protriptyline levels ranged from 10.4 to 22.3 ng/ml and were reached 6 to 12 hr after the oral dose. The mean protriptyline half-life (t1/2) was 74.3 hr and ranged from 53.6 to 91.7 hr in individual subjects, confirming the long t1/2 of protriptyline reported by Moody and associates. The estimated first-pass metabolism of protriptyline was relatively small, ranging from 10% to 25% of the oral dose, assuming complete absorption. The mean volume of distribution was 22.5 L/kg and ranged from 15.0 to 31.2 L/kg. No relationship was found between the kinetics of protriptyline and those of doxepin studied previously in 7 of the 8 subjects.

Adult↗

Primary and secondary affective disorders: baseline characteristics of unipolar patients.

We studied 569 patients with RDC non-bipolar major depressive disorder from the clinical portion of the NIMH Program on the Psychobiology of Depression. Primary (n = 327; never had a non-affective disorder), secondary (n = 191; had a non-affective disorder before ever having a major depressive episode), and "complicated' (n = 51; had at least one depressive episode before and another since developing a non-affective condition) patients were compared on demographic variables, past episodes of depression, past treatments received, and symptoms seen in the index episode. For most characteristics, the groups fell in the order primary, secondary, complicated, such that complicated cases had the earliest onset, the longest duration and the greatest severity in the index episode. These data do not discriminate between two hypotheses: that secondary and complicated depressions are basically depressions which happen to occur in a non-affectively ill person, or that they are different disorders which are distinguished clinically by characteristics related to severity.

Adult↗

Bipolar versus unipolar and primary versus secondary affective disorder: which diagnosis takes precedence?

The primary versus secondary distinction is often used as a way of subtyping depression. Its applicability to bipolar disorders has been unclear. This report examines the relative primacy of the bipolar versus unipolar distinction as compared to the primary versus secondary distinction in a sample of 955 patients in the NIMH Collaborative Study of the Psychobiology of Depression. These patients are divided into nine groups of the basis of whether they are bipolar I, bipolar II, or unipolar, and whether they are primary, 'pure' secondary, or 'complicated' secondary (i.e. bipolar I primary, bipolar I pure secondary, bipolar I complicated, etc.). Three sets of variables are used to determine the predictive validity of these various subtypes: data concerning age of onset and phenomenology of current episode, outcome, and familial prevalence. In general, data from these three sets of validators suggest that the bipolar distinction takes precedence over the primary versus secondary distinction. Within bipolars, there is little value in further subtyping into primary versus secondary.

Adult↗

Course of treatment received by depressed patients.

Using data from an observational study of affective disorders, we describe the rates of transition among levels of antidepressant treatment for subjects with Major Depressive Disorder (MDD), and relate these changes to changes in clinical status. We report on the treatment received during the first 10 years of follow-up in the Collaborative Depression Study by 555 patients with a diagnosis of MDD of at least one month's duration. This work extends the initial examination of treatment received during the first eight weeks after entry into this study that showed depressed patients to be on low levels of treatment. Multiplicative intensity models which generalize survival analysis models were used to analyse these data. Description of the course of treatment of these depressed patients shows that low levels of treatment persist for these patients across subsequent episodes, and that these episodes, like the index one, are characterized by extended time in a symptomatic subcriterion state after acute symptoms have improved. These long-term descriptions of treatment support the initial hypothesis that these CDS patients were undertreated. The long-term tendency toward undertreatment seems to persist even as newer treatments become available and widely accepted in practice.

Acute Disease↗

Charting patients' course: a comparison of statistics used to summarize patient course in longitudinal and repeated measures studies.

Investigators conducting longitudinal studies of psychiatric illnesses often analyze data based on psychiatric symptom scales that were administered at multiple time points. This study examines the statistical properties of seven indices that summarize patient long-term course. These indices can be used to compare differences between two or more groups or to test for changes in symptoms over time. They may also be treated as outcome measures and correlated with other clinical variables.The performance of each of the seven indices was assessed using data from two large ongoing studies of psychiatric patients: a longitudinal study of affective disorders and a longitudinal study of first-episode psychosis. These two datasets were subjected to bootstrapping techniques in order to calculate both type I error rates and statistical power for each summary statistic. Of the seven indices, Kendall's tau performed the best as a measure of patients' symptom course. Kendall's tau appears to offer more statistical power to detect change in course, yet its average type I error rate was comparable to the other indices.

Adult↗