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Biomedical subjects

M Ansseau

Publications and source records attributed to M Ansseau.

At least 163 records · Page 9Linked to original sources

Dexamethasone suppression test and MMPI scales.

In 42 major depressive inpatients, we analyzed the relationship between dexamethasone suppression test (DST) results and Minnesota Multiphasic Personality Inventory (MMPI) scales. Cortisol levels following DST were positively correlated with the depression as well as the social introversion MMPI scale scores, and negatively correlated with the hypomania scale scores. DST nonsuppressor depressives (n = 15) exhibited significantly higher scores on the social introversion scale and significantly lower scores on the hypomania subscale than DST suppressors (n = 27). Moreover, stepwise discriminant analysis using the hypomania score was able to correctly classify 71% of the sample according to DST dichotomy, whereas the association of other scales did not significantly improve the classification. Therefore, these results support a relationship between DST and depressive/manic psychopathology rather than anxious psychopathology.

Adolescent↗

Central dopaminergic and noradrenergic receptor blockade in a patient with neuroleptic malignant syndrome.

During treatment with clomipramine and haloperidol, a 54-year-old depressed woman exhibited a typical neuroleptic malignant syndrome (NMS). Among results of biologic tests performed at least 2 weeks after discontinuation of all psychotropic treatment, the absence of normal growth hormone response after both apomorphine and clonidine challenge tests and increased levels of cerebrospinal fluid homovanillic acid and urinary 3-methoxy-4-hydroxyphenylglycol suggest that NMS may be related to central dopaminergic and possible alpha-noradrenergic receptor blockade.

Clomipramine↗

Initial study of methylclonazepam in generalized anxiety disorder. Evidence for greater power in the cross-over design.

The anxiolytic activity of methylclonazepam was compared to lorazepam and placebo in a double-blind, randomized cross-over study, using a latin square design, in 18 inpatients meeting Research Diagnostic Criteria for Generalized Anxiety Disorders. Patients presented at least 1 year of symptomatology and had a minimum score of 20 on the Hamilton Anxiety Scale, despite chronic anxiolytic pharmacotherapy. Daily dosage was flexible, from three to six tablets of methylclonazepam 1 mg, lorazepam 2.5 mg, or placebo. Clinical evaluation included Hamilton Anxiety Scale, Clinical Global Impression (CGI), a side-effects checklist, completed every 2 days, and the global preference of the patient for one of the treatment periods. Results showed a highly significant superiority of both benzodiazepines over placebo on the Hamilton Scale (P less than 0.000001) and CGI (P less than 0.001), and also a significant superiority of methylclonazepam over lorazepam on the Hamilton Scale (P less than 0.01), CGI-1 (P less than 0.01), and in the number of patient preferences (14 versus 1; P less than 0.001), with no significant differences in side-effects or related to position in the trial. These results support the value of the cross-over design in chronic and severe anxious inpatients for the demonstration of differences in efficacy between anxiolytic pharmacotherapies.

Adult↗

Internight variability of REM latency in major depression: implications for the use of REM latency as a biological correlate.

The internight variability in REM latency in 92 drug-free inpatients with major depressive illness was recorded for 4 consecutive nights and subsequently assessed. Individual coefficients of variation in REM latency [CV = (standard deviation of mean REM latency for 4 recording nights/4-night mean REM latency) X 100] ranged from 5.1 to 121.7, with a mean of 37.0 (SD = 27.3) and a median of 27.4. CV was positively correlated with both age (p less than 0.05) and age at onset of depressive illness (p less than 0.01). Male patients showed more variability in REM latency than female patients (p less than 0.05); likewise, the subgroups of patients who either were incapacitated or had bipolar II illness showed greater variability in REM latency in comparison with the remainder of the sample (p less than 0.05). When the entire patient sample was stratified by CV into three equal subgroups, the subgroup of patients defined by the highest CV presented the longest sleep latency (p less than 0.05) and the shortest REM latency (p less than 0.0001). No other clinical or polysomnographic correlates of REM latency variability were noted nor was REM latency variability related to severity of illness, other subtypes of illness, or clinical response to antidepressant therapy. In selecting REM latency data for assessment of diagnostic sensitivity, the use of the shortest REM latency from at least 3 consecutive nights yielded a higher sensitivity (74%-81%) than did the use of any one individually specified night (50%-56%) or different internight means (49%-52%). The same conclusion applied when patient age was taken into account. These results have implications for standardizing the use of REM latency as a biological correlate in major depression.

Adult↗

"Paradoxical" shortening of REM latency on first recording night in major depressive disorder: clinical and polysomnographic correlates.

Among 92 inpatients with major depressive disorders, variability in REM latency (RL) during the first two recording nights was assessed by means of an "adaptation coefficient" (AC = night 1 RL--night 2 RL X 100 divided by mean RL for nights 1 and 2). Although mean RL was very similar for both nights (48.1 and 50.7 min), individual ACs showed a gaussian distribution [range: -176.5-171.4; mean: -1.2 (67.3); median: -4.4]. Forty-two patients (45.7%) exhibited shortening of RL on night 2 compared with night 1 (positive AC, corresponding to an "expected" evolution), 48 patients (52.2%) displayed the opposite pattern (negative AC, corresponding to a "paradoxical" evolution), and two patients had identical values on both nights. Extent of increase in RL from first to second night (i.e., extent of "paradoxical" evolution) correlated significantly with increasing duration of current episode, earlier age of onset, and poorer clinical response to tricyclic antidepressants. A cutoff AC of -7 correctly classified 62% of patients according to treatment response. The research diagnostic criteria-based retarded subtype of depression was associated with a more negative AC (i.e., a more "paradoxical" evolution), and the situational subtype was associated with a more positive AC (i.e., a more "expected" evolution) than the remainder of the sample. The subgroup with the most negative ACs (i.e., largest increases in RL from first to second night) also had longer sleep latencies, whereas the subgroup with the most positive ACs (i.e., largest decreases in RL) had higher REM activity and REM density as compared with the remainder of the sample. These results suggest that RL in major depression is not a static parameter and that the study of its within-subject variability can be helpful for diagnostic confirmation and prediction of treatment response.

Adaptation, Physiological↗

Release of human neurophysin I during insulin-induced hypoglycemia in depressed patients is abolished after recovery with clomipramine treatment.

Release of human neurophysin I (hNp I) and neurophysin II (hNp II) during insulin-induced hypoglycemia was studied in 10 unipolar depressed women before and after 4-5 weeks of standard antidepressant drug treatment with daily intravenous infusions of clomipramine. Before treatment, a significant increase of hNp I but not of hNp II serum levels in response to hypoglycemia was observed. At retest during clomipramine administration, a marked clinical amelioration occurred in all patients as determined with the Hamilton Rating Scale for Depression; the hNp I response to insulin was abolished, but no effect on hNp II concentration could be demonstrated. No correlation was found between the degree of the depression score decrease and the amplitude of the inhibition of hNp I release or serum levels of clomipramine or its metabolite, desmethylclomipramine. The meaning of this difference in reactivity of the neurohypophyseal system in the course of depressive illness, based on the pharmacological and biochemical profiles of clomipramine action, is discussed.

Blood Glucose↗

Diagnostic performance of the thirty-four hour dexamethasone suppression test.

The performance of the dexamethasone suppression test (DST) in the diagnostic confirmation of endogenous depression was compared according to two times of blood collection--1600 hr on day 2 (usual sample) and 0800 hr on day 3 (34 hr after dexamethasone intake)--in 14 endogenous depressives and in a control group of 17 psychiatric inpatients with other diagnoses. For the day 2 (1600 hr) sample, a 5 micrograms/dl cortisol concentration represented the best cut-off score, with sensitivity of 57% specificity of 88%, and diagnostic confidence of 80%. For the day 3 (0800 hr) sample, the best cut-off score was 20 micrograms/dl, with the same sensitivity (57%) but there was a decrease of both specificity (to 76%) and diagnostic confidence (to 67%). The mean cortisol levels were much higher on day 3 than on day 2, suggesting that the inhibitory activity of dexamethasone was no longer present.

Adult↗

[Value of the sleep EEG as a biological marker of depressive states. Comparison with 3 neuroendocrine tests].

In a sample of 12 endogenous depressive inpatients (8 primary and 4 secondary depressives), we compared the diagnostic usefulness of REM latency (recorded during at least 4 consecutive nights) with 3 neuroendocrine tests: dexamethasone suppression test and GH response after clonidine (a alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) challenges. Shortened REM latency (less than 50 min during at least 1 night) was present in 67% of depressives. However, REM latency presented a clear night to night intra-patient variability that makes it necessary to record at least 3 consecutive nights for the best sensitivity. Non-suppression after dexamethasone was present in 50% of depressives, blunted GH response after clonidine, in 75% and blunted response after apomorphine, in 42%. A total of 92% of patients exhibited at least one abnormal biological parameter (100% of primary and 75% of secondary depressives); 67% of patients exhibited at least two disturbed parameters and these patients constituted the whole primary depressive group (100%). These results show that these 4 potential biological markers of depression are not necessarily distributed in the same population. This suggests the potential usefulness of their concurrent use for improved accuracy of diagnosis.

Adult↗

Extrapyramidal signs following zimelidine overdose.

A 35-year-old woman with depression attempted suicide by taking an overdose of zimelidine (5 g), which was confirmed by zimelidine and norzimelidine plasma levels. Physical examination and repeat EKGs performed 2, 6, 9, and 12 hours later showed no alteration in her level of consciousness and only a slight increase in QT duration. However, the patient exhibited a distinct extrapyramidal syndrome, a finding consistent with animal data suggesting that zimelidine may possess some dopamine-receptor blockade properties.

Adult↗

Duration of benzodiazepine clinical activity: lack of direct relationship with plasma half-life. A comparison of single vs divided dosage schedules of prazepam.

The anxiolytic activity and tolerance of two dosage schedules of prazepam, a long plasma half-life benzodiazepine, were compared under double-blind conditions in two groups of 10 inpatients each who met Research Diagnostic Criteria for Generalized Anxiety Disorder and presented chronic and severe symptomatology. Patients received prazepam 40 mg per day on one of two dosage schedules: divided dosage (DD) - 10 mg in the morning and at noon and 20 mg in the evening; or single dosage (SD) - 40 mg in the evening. The 3 weeks of therapy were preceded and followed by 1 week of wash-out for baseline and follow-up assessments, which were performed weekly with the Hamilton Anxiety Scale, Clinical Global Impression, rating of morning drowsiness and evening worsening of symptoms, and patient self-rating of anxiety by means of a visual analogue scale performed both in the morning and in the afternoon. The results showed a clear superiority of the DD over the SD schedule: better anxiolytic efficacy on the Hamilton Anxiety Scale (P less than 0.0005) and on both morning and afternoon visual analogue scales (P less than 0.01 and P less than 0.0002); less morning drowsiness (P less than 0.0001); and steadier anxiolytic effect during the daytime, as globally rated by the investigator (P less than 0.0001) or measured by morning-afternoon differences on the visual analogue scale (P less than 0.005). These results suggest that plasma pharmacokinetics alone may not be sufficient to predict the duration of benzodiazepine anxiolytic activity.

Adult↗

Double-blind clinical study comparing alprazolam and doxepin in primary unipolar depression.

The therapeutic effect and safety of alprazolam and doxepin were studied in 126 outpatients suffering from primary unipolar depression. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with a flexible dose of 1.0-4.5 mg of alprazolam and 50-225 mg of doxepin per day. The mean final doses were 2.7 mg for alprazolam and 137.5 mg for doxepin. The results indicate that alprazolam and doxepin were equally efficacious. The incidence of side-effects was lower in the alprazolam treatment group.

Adolescent↗

Concurrent use of REM latency, dexamethasone suppression, clonidine, and apomorphine tests as biological markers of endogenous depression: a pilot study.

In a sample of 12 major depressive inpatients, endogenous subtype (8 primary and 4 secondary) defined by Research Diagnostic Criteria, we compared the sensitivity of four potential biological markers: latency of rapid eye movement (REM) sleep (recorded during at least 4 consecutive nights), dexamethasone suppression, and the clonidine and apomorphine tests. Shortened REM latency (less than 50 minutes during at least 1 night) identified 67% of depressives (87% of primary and 25% of secondary); nonsuppression after dexamethasone identified 50% of depressives (62% of primary and 25% of secondary); blunted growth hormone (GH) response after clonidine identified 75% of depressives (100% of primary and 25% of secondary); and blunted GH response after apomorphine identified 42% of depressives (62% of primary and 0% of secondary). Ninety-two percent of patients were correctly identified by at least one biological marker (100% of primary and 75% of secondary depressives). Of 67% of patients positive on at least two biological markers, all were primary depressives (100%). These four biological markers do not necessarily identify the same population, suggesting that their concurrent use may yield the highest level of diagnostic sensitivity.

Adult↗

Use of saliva cortisol in the dexamethasone suppression test.

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 micrograms/dl) and plasma free cortisol (0.15 microgram/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.

Adolescent↗

Self-reports of anxiety level and EEG changes after a single dose of benzodiazepines. Double-blind comparison of two forms of oxazepam.

A new formulation of oxazepam especially designed to increase the speed of absorption and eliminate the need to use water (freeze-dried dosage formulation; FDDF) was compared in double-blind and crossover conditions with the standard tablets of the same compound. 5 inpatients with generalized anxiety disorder received at 1-week intervals a single 30 mg dose of one of the compounds. Every 8 min for 96 min after drug intake, they completed a battery of visual analogue scales and had an EEG recording with computerized spectral analysis. Results showed a significantly more rapid onset of activity of FDDF oxazepam for both the self-reports of anxiety level (p less than 0.005) and the specific beta 2 EEG changes (p less than 0.0001), which were significantly correlated (r = -0.73; p less than 0.01). Moreover, all patients rated FDDF oxazepam as having faster onset of action in clinical change than regular tablets (p less than 0.05). This study shows the value of visual analogue scales, pharmaco-EEG, and crossover design in well-selected anxious inpatients in substantiating clinical differences between anxiolytic pharmacotherapies.

Adult↗