Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials.

Tianeptine is a new antidepressant effective against anxiety accompanying mood disturbances. Its clinical properties have been assessed by double-blind controlled studies (versus imipramine, amitriptyline, nomifensine, viloxazine) in depressed patients fulfilling the diagnostic criteria of the DSM III: single recurrent major depressive episodes without melancholia or psychotic features, and dysthymic disorders. The authors have concluded that tianeptine is effective in depressive disorders as shown both by depression rating scales and subjective impressions of treated patients. This improvement increases regularly with time. Seventy-eight percent of patients were considered to be "responders" at the end of the treatment with tianeptine. Antidepressant activity of tianeptine is equally present in depressive states appearing after withdrawal from alcohol. In depressed patients with anxiety, the results also reveal the efficacy of tianeptine on anxiety symptoms. Tianeptine, in addition, shows a marked action on somatic complaints. These results have been confirmed by open long-term trials, particularly in the elderly. Tianeptine can be placed in a middle position in the bipolar classification, between the sedative and stimulant antidepressants. Its antidepressant and anxiolytic properties and its action on somatic complaints make the drug particularly suitable for the treatment of the entire range of depressive symptomatology.

Long-term administration of tianeptine in depressed patients after alcohol withdrawal.

Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.

Long-term use of tianeptine in 380 depressed patients.

Tianeptine is a new tricyclic compound whose principal action is to increase the reuptake of serotonin. In a multicentre trial in which 380 depressed patients were treated for one year, tianeptine produced a significant reduction in the MADRS scores from day 14, with a sustained reduction maintained for up to 12 months; other measures of efficacy (HRSA, HSCL, and CGI) also reflected the improvement. Only 11% of patients withdrew because of recurrence of depression and 2% because of side-effects, which were mainly drowsiness, irritability, and gastrointestinal disturbance. Apart from a minor reduction in heart rate, unaccompanied by any conduction changes, no clinically relevant changes in vital signs or laboratory tests were seen. Seven subjects who attempted suicide by tianeptine overdose had favourable outcomes, in spite of also taking other psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms was seen after treatment was stopped. These results suggest that tianeptine has the potential to provide safe antidepressant activity in both the acute and chronic phases of treatment.

[Tolerability of tianeptine in 170 patients with depression treated during one year]. / Acceptabilité de la tianeptine chez 170 patients déprimés traités un an.

Tianeptine, a new antidepressant, has a tricyclic molecular structure. Its main biochemical activity consists of an increase in the reuptake of 5 HT both in men and animals, after acute and chronic administration. Tianeptine demonstrated its antidepressive clinical efficacy in several double-blind versus reference drug trials. A multicentre open trial, including depressed patients enabled us to evaluate the safety of tianeptine and to control the maintenance of the therapeutic efficacy in the course of its long-term prescription. Depressed patients included showed a major depressive episode, single (296.22) or recurrent (296.32) without melancholia or psychotic features, or a dysthymic disorder (300.40), according to DSM III criteria. A minimum MADRS score of a least 25, and the informed consent of the patients were required. The dose of tianeptine was 3 tablets per day (12.5 mg/tablet) with the possibility of increasing to 4 or decreasing to 2 tablets per day, depending on the symptomatology. Therapeutic efficacy was evaluated by item 1 and 2 of the Global Clinical Impression (CGI), the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS) and the Hopkins Symptom Check-List (HSCL). Clinical and paraclinical safety were evaluated by CGI item 3, standardized ratings of patients' complaints (CHESS 84), interruption for side effects, evaluation of blood pressure, weight, biological parameters, EKGs. This intermediate evaluation concerns the first 170 depressed patients treated over a one-year period as well as the total group of patients included (n = 447).(ABSTRACT TRUNCATED AT 250 WORDS)

[Congenital long QT syndrome in newborns]. / Syndrome du QT long congénital de révélation néonatale.

UNLABELLED: The perinatal manifestations of the long QT syndrome are rare, but early diagnosis and therapy are necessary to prevent sudden death. CASE REPORTS: A long QT syndrome was diagnosed in two neonates who presented with foetal bradycardia. In one case, a mutation in the gene KCNQ1 was identified, and a long QT syndrome was diagnosed in the mother and two brothers of the neonate. On beta-blocker therapy, one infant became free of long QT syndrome related symptoms, but a sudden death of the second infant occurred. CONCLUSION: The long QT syndrome should be considered in the differential diagnosis of foetal bradycardia. Early treatment of the neonate and his family may prevent ventricular arrhythmias and sudden death.

[Therapeutic effects of tianeptine in patients with depression and anxiety disorders with or without associated alcoholism]. / Effets thérapeutiques de la tianeptine chez des patients déprimés et anxieux avec ou sans alcoolisme associé.

Tianeptine is a new tricyclic antidepressant. Double blind studies comparing tianeptine with imipramine and amitriptyline have shown the effectiveness of tianeptine's antidepressor action, its properties of non-specific symptoms related to behaviour disorders (anxiety, inhibition ...) and its action on somatic complaints expressed by depressed patients. Tianeptine is an effective antidepressant in cases of depression with anxiety or alcoholism and also leads to good therapeutic response in cases of dysthemia. In depressions with melancholy and endogenous criteria, the expected percentage of responding patients has been observed with tianeptine. A reinforcement of the therapeutic effect has been demonstrated after 6 months of treatment. Its excellent clinical and parclinical acceptability, especially in long term treatment of patients at risk such as elderly depressed patients or alcoholic patients, makes tianeptine a first intention antidepressant.

[Cardiovascular tolerance to tianeptine]. / Acceptabilité cardiovasculaire de la tianeptine.

The cardiovascular effects of tianeptine were assessed by a specific placebo-controlled trial in healthy volunteers and by heart rate, blood pressure and electrocardiogram data analyses in five studies enrolling depressed patients. In two of these studies the effects of tianeptine were compared to those of amitriptyline. The three other studies were performed as open, long-term trials (up to one-year treatment) in large populations of patients (more than 3,300 patients). The findings show that tianeptine does not modify heart rate, blood pressure, conduction or ventricular function. Tianeptine was well tolerated in depressed patients and induced no significant changes at the current dosage in treatment periods from three-months to one-year even in elderly patients, patients with cardiovascular abnormalities or alcoholic patients. Fewer cases of orthostatic hypotension were observed than with other antidepressants. Suicide attempts with tianeptine overdosage did not lead to death due to cardiovascular complications.

[Depression in elderly patients. Value of tianeptine in 140 patients treated for 1 year]. / La dépression du sujet âgé. Intérêt de la tianeptine chez 140 patients traités pendant 1 an.

An open multicenter study of the efficacy and acceptability of tianeptine, a new antidepressant structurally related to tricyclic antidepressants, was conducted by 36 gerontologists. There were 228 patients in the study; 140 were treated for one year. The patients' overall MADRS score started to decrease on day 14 and continued to decline to month 3. An improvement in depression was again observed near the end of the treatment period from month 9 to month 12. This pattern of improvement was also found with the HARS, the first item on the CGI scale and the Zung self-evaluation scale. These findings demonstrate the beneficial effect of long-term treatment in depressed elderly patients. Ten patients (4.4 percent) dropped out because of side effects: mainly drowsiness, anxiety or gastrointestinal disorders. The benefit/risk ratio (CGI, item 3), an expression of treatment effectiveness and acceptability, was very satisfactory even in these elderly patients. Regularly performed laboratory tests and clinical examinations (including weight and blood pressure) revealed no significant changes. Finally, somatic disorders, essentially cardiovascular and neurological diseases often occurring in depressed patients, remained remarkably quiescent throughout the entire treatment period.

[An unrecognized neonatal emergency: extensive hematoma of the scalp. 5 cases]. / Une urgence néonatale méconnue: l'hématome extensif du cuir chevelu. 5 observations.

BACKGROUND: Subgaleal hemorrhage results from a pericranial effusion of blood subsequent to neonatal trauma. This exceptional situation compared with other pericranial effusion conditions in the neonate may be life-threatening. CASE REPORTS: We report the obstetrical and neonatal data in 5 cases of subgaleal hemorrhage observed in our unit over an 8-year 8-month period. We detail one particularly demonstrative case which illustrates the potentially serious course of certain clinical presentations. DISCUSSION: Subgaleal hemorrhage is a clinical diagnosis. Signs of hemorrhagic shock are associated with hemostasis disorders in the more severe forms of the condition. The main risk factor is instrumental delivery with suction. Careful monitoring is required.

Improving imbalanced scientific text classification using sampling strategies and dictionaries.

Many real applications have the imbalanced class distribution problem, where one of the classes is represented by a very small number of cases compared to the other classes. One of the systems affected are those related to the recovery and classification of scientific documentation. Sampling strategies such as Oversampling and Subsampling are popular in tackling the problem of class imbalance. In this work, we study their effects on three types of classifiers (Knn, SVM and Naive-Bayes) when they are applied to search on the PubMed scientific database. Another purpose of this paper is to study the use of dictionaries in the classification of biomedical texts. Experiments are conducted with three different dictionaries (BioCreative, NLPBA, and an ad-hoc subset of the UniProt database named Protein) using the mentioned classifiers and sampling strategies. Best results were obtained with NLPBA and Protein dictionaries and the SVM classifier using the Subsampling balancing technique. These results were compared with those obtained by other authors using the TREC Genomics 2005 public corpus.

Simulation of pulmonary damages induced by inhaled Cl2 on the bronchial tree.

We have measured the change of lung mechanical parameters on isolated rabbit lungs exposed to chlorine gas (Cl2). Experimental results show parallel increase in elastance and resistance of impaired lungs. We tried to determine whether this may be explained by a reduction of the ventilated areas in the lung, consecutive to closure of some airways. We have been tried to simulate these experimental results by studying the effects of various airways occlusions imposed on two concurrent models (symmetrical and dissymmetrical) of the tracheo-bronchial tree. For each model, we successively evaluated the resistance of the normal lung, simulated a partial peripheral airways occlusion and estimated the induced changes in total resistance. Analytical expressions of the "occluded lung" elastance and resistance have been found for the symmetrical model but not for the dissymmetrical model (a graphical approach is proposed). With the symmetrical model, simulated results are comparable to experimental ones when the occlusion level is proximal. Whatever the dissymmetry level (delta) of the fractal tree model, we could not simulate the expected increase in resistance with the observed increase in elastance. We conclude that either the occlusion in non homogeneous or the lung impairment is not only a reduction in ventilated areas.

Development of a population pharmacokinetic database for tianeptine.

Two thousand three hundred and thirty five plasma concentrations of tianeptine from 112 patients enrolled in nine studies of tianeptine pharmacokinetics performed prior to the marketing of the drug were pooled for analysis using mixed-effect modeling. Studies represented a combination of single dose and multiple dosing at steady-state. Tianeptine plasma concentration time data were fit to a two compartment model with first order absorption using the NONMEM computer program. The results of this analysis suggested that alcoholism is associated with significant increase in clearance (124% increase) and volume of the central compartment (161% increase). The volume of the peripheral compartment is significantly lower in women (31% decrease) and in depressed patients (59% decrease). The population mean (interindividual variability) clearance was equal to 0.17 l.h-1 x kg-1 (28.6%), the volume of central compartment was 0.13 l.kg-1 (60.4%), intercompartmental clearance was 0.07 l.h-1 x kg-1 (30.1%), volume of the tissue compartment was 1.17 l.kg-1 (28.3%), and the absorption rate constant was 0.63 h-1 (21.8%). The residual variability was approximately 30% at concentrations expected during clinical use of the drug. Because of the increased clearance, alcoholic patients would be expected to have significantly reduced concentrations during steady-state dosing. These population parameters provide a basis for developing initial dosing recommendations and for performing bayesian evaluations of drug concentrations obtained in post-marketing studies.

Predictive performance of population pharmacokinetic parameters of tianeptine as applied to plasma concentrations from a post-marketing study.

The predictive ability of population pharmacokinetic parameters of tianeptine, obtained from a mixed effect analysis of pre-marketing pharmacokinetic studies, was evaluated using tianeptine plasma concentrations obtained during a large multi-center post-marketing surveillance study. The mean prediction error was 7.8 ng.ml-1 and the root mean square prediction error was 52.1 ng/ml when initial estimates of population pharmacokinetic parameters were used to predict drug concentrations in one half of the post-marketing data. When the population parameters were revised to reflect the data collected in the first half of the post-marketing study, the mean prediction error was reduced to -3.2 ng.ml-1 and the root mean square prediction error was reduced to 29.5 ng.ml-1. These results suggest that population pharmacokinetic parameters obtained from pre-marketing data may not accurately predict drug concentrations in patients receiving the drug in the post-marketing setting. Once the population parameters are updated to reflect data from the post-marketing period, the predictive ability of the data-base increases, but substantial variability in the prediction error remains.