The short- and long-term efficacy of paroxetine HCl: A. Data from a 6-week double-blind parallel design trial vs. imipramine and placebo.
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Biomedical subjects
Publications and source records attributed to E D Peselow.
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To evaluate the dexamethasone suppression test (DST) as an aid in monitoring clinical recovery, the authors evaluated 127 outpatients with major depression who received the DST during depression and after clinical recovery. Although DST response varied among the 73 patients who met the Research Diagnostic Criteria for definite endogenous depression, their mean postdexamethasone plasma cortisol level was significantly higher during depression than after recovery. However, the DST's utility in monitoring long-term outcome was not great, as there was a high chance of remaining stable for 6 months after recovery regardless of cortisol value during depression or after recovery.
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The predictive value of the dexamethasone suppression test (DST) was evaluated in two consecutive clinical trials involving 99 individuals treated with amitriptyline or desipramine. Following one week observation, and following one week on low-dose desipramine or amitriptyline (50 mg), all patients who remained depressed (Hamilton score 16 or greater) were given a full clinical trial of either desipramine or amitriptyline (150-300 mg/day) over a minimum 3-5 week period. In all, 68 patients required this trial, 31 receiving amitriptyline and 37 receiving desipramine. For these patients there was no relationship between DST suppression/non-suppression vs clinical response to either desipramine or amitriptyline. There was a non-significant trend for suppressors (negative DST) to respond either spontaneously or to low-dose desipramine or amitriptyline as opposed to non-suppressors (positive DST).
Seventy patients with unipolar major depressive disorder were treated with fluoxetine or placebo in a 6-week double-blind trial and were evaluated by changes in scores on the Hamilton Rating Scale for Depression (HAM-D) and the global improvement measure of the Clinical Global Impressions (CGI) scale. High correlations were found between the changes in HAM-D scores from baseline to endpoint and the final CGI improvement ratings. In patients with moderate depression (baseline HAM-D score of 20 or more), the differences in endpoint analysis between active treatment and placebo groups were significant. A persistent pattern of improvement was noted in 27% of those receiving fluoxetine but in none of those receiving placebo. Physician and patient evaluations as determined by the improvement measure of the CGI were closely correlated.
The predictive value of the dexamethasone suppression test (DST) was evaluated in two consecutive double-blind, placebo-controlled trials evaluating 61 depressed inpatients randomized to either one of two drugs, sertraline or oxaprotiline, or placebo over a 4-week clinical trial. For 30 patients who completed at least 3 weeks of double-blind treatment on either drug, the initial DST was not predictive of response to drug treatment. For the 17 patients who completed at least 3 weeks of double-blind treatment on placebo, the presence of a positive DST predicted a statistically significantly poorer response to placebo as opposed to a negative DST. These preliminary findings suggest that for depressed individuals who present with a positive DST, remission without active medication is less likely and somatic treatment should be considered.
75 outpatients who presented to an affective disorder clinic received the dexamethasone suppression test (DST). Following 1 week observation, and following 1 week on low-dose imipramine HCl, all patients who remained depressed (Hamilton score 16 or greater) were given a full clinical trial of imipramine HCl (150-300 mg/day) over a minimum 3- to 5-week period. Of the 45 patients who required this trial and who received imipramine HCl for at least 3 weeks, there was no relationship between DST suppression or nonsuppression vs. clinical response to imipramine HCl. There was a statistically significant trend for suppressors (negative DST) to respond either spontaneously or to low-dose imipramine HCl as opposed to nonsuppressors (positive DST).
A case is reported of a patient who died as a result of lithium toxicity. Brain lithium levels and changes in brain glycine levels are discussed.
Blunted responses to thyrotropin-releasing hormone (TRH) stimulation have been found consistently in depressed patients, and have been reported in other affective disorders as well. In a smaller number of schizophrenic subjects, TRH tests have generally been normal. Thus, it has been suggested that this test may have diagnostic utility in distinguishing schizophrenia from affective disorders. In the present study the TRH test was performed upon a sample of 51 subjects that included 17 schizophrenics in order to further study the diagnostic or symptom specificity of this endocrine test. Abnormal TRH tests were present in both schizophrenic and affectively disturbed patients. There were no correlations with ratings of depression or other aspects of psychopathology. Factors which may have previously obscured abnormal TRH tests in schizophrenia are discussed.
In addition to its incorporation into proteins, glycine functions as both a regulator of one-carbon metabolism and as an inhibitory neurotransmitter. Clinical recognition of the hyperglycinemias and reported elevations of erythrocyte glycine concentrations in patients with bipolar disorders have implicated this amino acid in the etiopathology of some neuropsychiatric disorders. Moreover, chronic lithium administration, an almost specific intervention for the treatment and prophylaxis of bipolar disorders, has been shown to induce elevations in brain and erythrocyte glycine levels. In view of glycine's complex metabolic interrelationships and neurotransmitter function, additional research exploring its possible role in either affective illness or lithium's action is indicated.
In contrast to a recently published report by Amsterdam and associates, the authors noted a higher frequency of abnormal dexamethasone suppression test results in 88 outpatients with primary depression (particularly the endogenous subtype) than in 49 normal controls.
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Red blood cell (RBC) glycine levels were examined in 27 bipolar patients, treated with lithium carbonate for a minimum of 8 months, who were either hypomanic, depressed, or euthymic in their mood. We found no difference in the RBC glycine or in the RBC: plasma glycine ratio between the hypomanic, depressed, or euthymic patients (P less than 0.1). There were statistically significant differences in RBC glycine levels in lithium-treated euthymic patients and normal controls. There was a strong positive correlation between serum lithium levels and both RBC glycine levels and the RBC: plasma glycine ratio.
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