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M Ansseau

Publications and source records attributed to M Ansseau.

At least 145 records · Page 8Linked to original sources

[Relationship between dexamethasone suppression test and contingent negative variation in major depressive patients].

We tried to relate two different indexes sensitive to the perturbations induced by major depression: the Dexamethasone Suppression Test or DST (Caroll, 1982) and the Contingent Negative Variation (CNV). The question was whether abnormalities in cortisol levels, following dexamethasone would enlight the modifications observed in CNV parameters and other electrophysiological indexes (EEG spectrum, reaction time). In 61 major depressive patients, 29 being DST-non-suppressors, we calculated differences in electrophysiological variables according to DST suppression or not, but we were not able to evidence significant differences between the groups. However, there were correlations between log-transformed levels of cortisol and on the one hand, CNV slope (r = -0.34, P less than 0.03) and on the other hand, reaction time (r = 0.45, P less than 0.01). Correlations between electrophysiological variables appeared in the sole suppressors group (e.g. CNV amplitude and alpha rythm reactivity; post-imperative variation and percent beta of the EEG spectrum). These results underline the complementary aspect of the two methods.

Adult↗

Comparison of sublingual and oral prazepam in normal subjects. II. Pharmacokinetic and pharmacodynamic data.

The pharmacokinetic profiles of oral and sublingual administrations of prazepam 20 mg to 5 normal volunteers were compared in order to explain the clinical observation that sublingual prazepam appears to exhibit sedative properties when compared to the same dose of oral prazepam. Blood samples for pharmacokinetic evaluation were collected just before drug intake and 7.5, 15, 22.5, 30, 45, 60, 90 min, 2, 3, 5, 6, 7, 8, 9, 10 and 24 h after drug intake. The study was performed in double-blind and crossover conditions. Serum levels of prazepam and its major metabolite N-desmethyl-diazepam were measured by HPLC. No prazepam was detected at a concentration higher than 20 ng/ml (limit of detection) whereas N-desmethyl-diazepam reached concentrations around 140 ng/ml. To correlate this observation with the clinical data, the affinity of prazepam and N-desmethyl-diazepam was compared measuring their ability to displace 50% of 3H-flunitrazepam bound to benzodiazepine receptors contained in synaptosomal preparation obtained from rat brain. N-desmethyl-diazepam was 17-fold more potent than prazepam. This data suggests that prazepam is a pro-drug which is transformed to the active compound N-desmethyl-diazepam and that the difference in clinical observation with both administrations could be correlated to N-desmethyl-diazepam concentration-time curves. Nevertheless, the comparison of the area under the N-desmethyl-diazepam serum concentration-time curves, the maximum concentrations, the times when the maximum concentrations were observed and the times needed to detect a significant level after oral and sublingual administration did not show statistical difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Blunted response of growth hormone to clonidine and apomorphine in endogenous depression.

We measured the growth hormone (GH) response to clonidine (an alpha-2-adrenergic agonist) and to apomorphine (a dopaminergic agonist) in 15 major endogenous and 15 minor depressive in-patients matched for gender and age. Results showed a significantly smaller GH response in the major depressives to both clonidine (P less than 0.01) and apomorphine (P less than 0.001). No significant difference existed between the two groups with regard to changes in blood pressure and pulse rate during either test. While major depressives showed a trend toward smaller sedative side-effects than minor depressives after clonidine, they showed significantly smaller sedative and gastro-intestinal side-effects after apomorphine. No significant correlation was present either in the major depressive or in the minor depressive group between the GH responses following clonidine and apomorphine challenges. These results support the hypothesis of both noradrenergic and dopaminergic neurotransmitter disturbances in major depression, with individual variability with regard to those biochemical anomalies.

Adult↗

Diagnostic performance of basal free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) ratio in endogenous depression: comparison with the dexamethasone suppression test.

We assessed the 8:00 AM ratio of free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in 56 endogenous depressive inpatients and in 22 normal volunteers. A ratio higher than 40 was associated with a diagnostic sensitivity for endogenous depression of 75%, a specificity of 95.5%, and a diagnostic confidence of 97.7%. These diagnostic results were at least equivalent to the Dexamethasone Suppression Test (DST) using a cortisol cut-off limit of 5 micrograms/dl. This may thus represent a simpler procedure than the DST in the diagnostic analysis of endogenous depression.

18-Hydroxydesoxycorticosterone↗

Neuroendocrine evaluation of catecholaminergic neurotransmission in mania.

Several lines of evidence suggest catecholamine overactivity (noradrenergic and/or dopaminergic) in mania. We studied the growth hormone (GH) response to clonidine (an alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) in seven inpatients meeting Research Diagnostic Criteria for mania. They had been completely drug free for at least 3 months before the neuroendocrine procedures and were age- and sex-matched to seven major depressive and seven minor depressive inpatients, drug free for at least 2 weeks. GH was assayed every 20 min for 40 min before and 120 min after either clonidine (0.15 mg i.v.) or apomorphine (0.5 mg s.c.), with an interval of at least 2 days between the tests. The three groups differed significantly in the GH peak response: after clonidine (mean +/- SD), 3.2 +/- 2.4 ng/ml in manics, 3.2 +/- 2.4 ng/ml in major depressives, and 13.2 +/- 8.7 ng/ml in minor depressives; after apomorphine, 10.5 +/- 7.4, 3.2 +/- 1.9, and 26.9 +/- 15.8, respectively. While there were significant differences between manics and minor depressives and between major and minor depressives after both clonidine and apomorphine, manics did not significantly differ from major depressives on either test. These results do not provide neuroendocrine support to the catecholaminergic hypothesis of manic disorders.

Adult↗

Intranasal oxytocin in obsessive-compulsive disorder.

A 55-year patient with obsessive-compulsive disorder showed clear improvement during 4 weeks of treatment with intranasal oxytocin compared to 4 weeks of intranasal placebo. This improvement was concurrent with the development of severe memory disturbances, supporting the amnestic properties of the peptide. However, the patient also developed psychotic symptoms and a marked decrease in plasma sodium and osmolality, which may have masked the obsessive symptomatology. This case highlights the need for careful monitoring in long-term oxytocin therapy.

Administration, Intranasal↗

[Sleep and depression: toward a standardization of the use of the latency of paradoxical sleep as a biological marker of major depression].

Among the various disturbances in sleep architecture among major depressive patients, the shortening of REM latency seems the most specific feature. Therefore, several groups have tested the usefulness of this parameter as a "biological marker" of major depression. The divergent results of those studies probably result from the marked differences in the methodology used. In this context, we compared the diagnostic sensitivity of various methodologies for selection of REM latency data among 92 major depressive inpatients recorded for 4 consecutive nights. The selection of individual night values or of mean values yielded very similar diagnostic sensitivity. However, the selection of the shortest REM latency from consecutive nights was associated with a higher diagnostic sensitivity, especially if at least 3 nights were included. After controlling for age, 87% of patients were identified by this methodology (sum of REM latency and age less than 90). Therefore we propose to standardize the methodology for use of REM latency: recording of 3 consecutive nights and selection of the shortest REM latency. If the sum of this value and of patient'age equals 90 or less, the diagnosis of major depression is supported.

Adolescent↗

Comparison of sublingual and oral prazepam in normal subjects. I. Clinical data.

Five normal volunteers received at a 2-week interval a single dose of sublingual or oral prazepam in double-blind and cross-over conditions. All subjects completed a battery of 15 visual analogue scales before drug intake and 7.5, 15, 22.5, 30, 45, 60, 90 min, 2, 3, 5, 6, 7, 8, 9, 10 and 24 h following intake whereas a computerized assessment of vigilance (reaction time) was performed before intake, 15, 30, 60 min, 2, 3, 6, 8, 10 h following intake. Subjects rated themselves significantly more feeble, clumsy, lethargic, and incompetent following sublingual as compared to oral prazepam while a trend in the same direction was noted for the adjectives muzzy and mentally slow. In contrast, reaction time did not exhibit significantly different changes over time between the two forms. These results suggest a subjectively more rapid onset of activity following sublingual compared to oral prazepam.

Administration, Oral↗

The AMDP-system in clinical psychopharmacology.

The AMDP-system, elaborated by the Association for Methodology and Documentation in Psychiatry, comprises three anamnestic forms and two rating scales on present psychopathological and somatic states. Moreover, three subscales have been developed in order to assess more specifically anxiety, manic/depressive, and schizophrenic symptomatology. The psychometric properties of the AMDP-system (interrater reliability, validity, homogeneity, sensitivity) and its availability in most European languages make it an ideal instrument for the assessment of clinical changes in drug trials, with the possibility of using the comprehensive scale for the early evaluation of a new drug and of reserving the short subscales for later clinical development.

Documentation↗

Evaluation of the sedative properties of PK 8165 (pipequaline), a benzodiazepine partial agonist, in normal subjects.

The sedative properties of two doses (50 and 150 mg) of a benzodiazepine partial agonist, PK 8165 (pipequaline), were compared to diazepam 10 mg and placebo in 12 normal volunteers. The assessment, performed before drug intake and 2 and 5 hours after drug intake, included a battery of visual analogue scales and standardized computerized tests (labyrinths, series of digits, colour test, and Zazzo test). Results showed that, at low dose, PK 8165 is not only devoid of any sedative effect but presents psychostimulating properties. In contrast, diazepam 2 hours after intake and PK 8165 150 mg, 5 hours after drug intake induced a significant decrease in performance compared to placebo. This study suggests that small doses of PK 8165 merits further development as an anxiolytic/psychostimulating drug devoid of sedative properties.

Adult↗