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Résumé: Notre étude a été réalisée en deux temps, durant l’année 2004, puis entre 2010 et 2012, et porte sur 2534 dossiers. L’objectif, outre confirmer ce qui est déjà décrit, comme une surconsommation massive de psychotropes par les personnes âgées, était d’observer si les nombreuses recommandations de ces dix dernières années étaient ou non suivies d’effets. Les prescriptions de ces produits dans les maisons de retraite sont-elles en régression ? Les populations étudiées sont conformes aux caractéristiques de la population française âgée. Mais, dans les résidences dédiées aux seniors, 80 % des personnes ont au moins un psychotrope, cela parmi les quatre familles les plus utilisées : anxiolytiques (30 % de malades), antidépresseurs (pour 44 %), hypnotiques (41 % des ordonnances), et antipsychotiques (28 % en 2012). Notre étude analyse les différents produits les plus prescrits, et, bien plus que le nombre de molécules, considère d’abord les doses administrées, en particulier lors des coprescriptions. Les doses importantes de traitement sont heureusement limitées à un malade sur dix, et, en huit ans, les pratiques se sont tout de même un peu modifiées, et cela de manière analogue dans les différentes institutions où ont été recueillies les données. [ABSTRACT FROM AUTHOR]

Abstract: The prevalence of benzodiapezine (BZD) consumption is assessed as 18.6% over 12 months and 11.3% over 30 days (Alonso et al., 2004 ). Within the framework of a transversal study with general practitioners (GP), 2000 GP representatives were picked by drawing lots. Three hundred provided information on 997 BZD-treated patients (15.6% patients/GP). An amount of 4.2% of the patients revealed the association of a length of treatment greater than recommended, with a notification to reduce or stop treatment by BZD, and others had expressed their wish to stop the treatment altogether. The weekly number of patients can be estimated at 47,189 for whom BZD withdrawal has been indicated. At the close of this work, a group of experts offered to draw up a procedure on in-care for BZD withdrawal in spa therapy for groups of six to 12 patients, stable regular BZD over-consumers for at least 3 months. This protocol associates daily crenotherapy treatment, personalized psychotherapeutic follow-up, consistent medical care and psycho-educative workshops. It is completed by a post-cure 6-month follow-up. There is an experimental phase under way in 2010 and 2011. [Copyright &y& Elsevier]

Abstract: Tryptic hydrolysate from bovine milk alpha-s1 casein (THC), a natural product, contains a specific active decapeptide called alpha-casozepine which shows interesting pharmacological properties. Preclinical and clinical trials, as well as tests carried out on both humans and animals (rats, dogs, cats) demonstrated certain qualities of this hydrolysate. It shows a marked affinity for GABA-A receptors with a benzodiazepine-like profile and a tranquilizing and antistress activity associated with good tolerance characterized, in particular, by the absence of any habituation, dependence, sedation, memory impairment and toxicity. THC is a nutritional supplement (French regulatory status) which cannot be used as a substitute for psychotropes, such as benzodiazepines, in the treatment of severe anxiety and sleep disorders in respect of the medical recommendations. However, it could be effective in cases of slighter signs of these disorders. It could also be appropriate in the medical prevention and follow-up of subjects who have difficulty adapting to changes and stressful situations of daily life. An original pilot clinical trial respecting good practice and representative of the cases observed by General Practitioners (GPs) showed the interest of a global management program for benzodiazepine withdrawal. This global management program which included the use of THC opened a new application for it in general practice. As a result of a certain neuropsychiatric similarity between man and the domestic dog, we took the opportunity of presenting this natural tranquillizer in its application in both human and veterinary medicine. [Copyright &y& Elsevier]

Abstract: ICU-acquired neuromyopathy (NMAR) and delirium are the two most frequent and severe neurological complications of intensive care medicine. Their mechanisms still remain to be elucidated. The objective of this review is to address the potential role of sedation in occurrence of these complications. There is no evidence that sedation is involved in NMARs. However, the hypothesis that muscle inactivity induced by sedation fosters NMAR is an argument to discontinue or reduce sedatives infusion whenever possible. It is also recommended not to administer propofol more than 48h at an infusion rate above 5mg/kg per hour in patients with systemic inflammatory response syndrome, because of the risk of propofol infusion syndrome, which includes notably rhabdomyolysis. The relationship between delirium and sedation are controversial because in most studies, patients were considered delirious though being still sedated and multivariate analysis was lacking. One study showed that lorazepam given continuously was an independent risk factor for daily transition to delirium 24h later with a 20% increase risk of every unit dose (expressed as loge mg). The impact of deepness, daily interruption or titration of sedation on the prevalence of delirium has never been assessed but it seems that deep sedation has to be avoided. [Copyright &y& Elsevier]

Abstract: We report a case of massive overdose of hydroxychloroquine treated with circulatory assistance by peripheral extracorporeal circulation (ECC). We expose the case of a 39-year-old woman who has ingested 12g of hydroxychloroquine with bromazepam, paroxetine, and zolpidem, in a suicide attempt. Patient has developed central nervous system depression, hemodynamic failure, life-threatening ventricular arrhythmias, and serious hypokaliemia. Initially the patient has received conventional treatment with gastric lavage and activated choarcal for gastrointestinal decontamination, vasculary expansion and vasopressive drugs, intubation and mechanical ventilation, high dose of diazepam, and potassium replacement. A ventriculary fibrillation was treated with external cardiac massage. In spite of this treatment, cardiogenic shock was uncontrolled, and imposed circulatory assistance. After extracorporeal circulation, we observed a spectacular improvement of hemodynamic parameters and electrocardiographic normalization at day one. Extracorporeal circulation could be used as a rescuer treatment of cardiotrope and hydroxychloroquine overdoses. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the influence of pretreatment with a low dose of etomidate (priming dose) on the incidence of etomidate-induced myoclonus. Study design: Prospective randomized double-blind study. Methods: Forty six patients ASA physical status I – II, scheduled for abdominal elective surgery, were allocated randomly to receive either pre-treatment 0.03 mg/kg of etomidate (priming group) or placebo (control group). Sixty-seconds after the pre-treatment was injected, anesthesia was induced with etomidate 0.3 mg/kg and 60 seconds later induction was completed with fentanyl (3 μg/kg) and vecuronium (0.1 mg/kg). The occurrence and intensity of myoclonus were graded clinically by a blinded observer as: 0=no myoclonus, 1=mild myoclonus, 2=moderate myoclonus and 3=severe myoclonus. Statistical analysis: Fisher test exact for qualitative variable and Student t-test for quantitative variables. Results: Demographic data and the average dose of etomidate used during the induction were similar in the 2 groups (0.29±0.032 mg/kg in the priming group and 0.30±0.029 mg/kg in the control group). Twenty patients (87%) in the control group experienced myoclonic movements whereas only 6 patients (26%) in the control group had such movements (P <0,001). Conclusion: Pretreatment with etomidate (0.03 mg/kg), given 60 seconds before induction of anesthesia, is effective at reducing etomidate-induced myoclonus, without related side-effect. [Copyright &y& Elsevier]

Abstract: The anxiodepressive symptomatology concerns a quarter of the studying population of sample and the factors cited are stress, solitude, relational problems, and addictions. Depressive students are likely to be more female and students in literary studies than scientific. Anxiolytics are the psychotrops most used by students (31% of students consume during courses, 23% occasionally and 8% regularly). The use of these medicines is significantly more frequent in the case of female students (40 vs 14%). Desbrosse-Baloche (2000) and the utilization of hypnotic, anxiolytic or antedepressor is higher in students of the Humanities and Letters. This disquieting situation has incited us to study some dysfunctional comportments in the light of transactional model of stress and coping. According to this transactional model, Lazarus et Folkman (1984) differentiate between two forms of evaluation that converge to describe the potential stressfull situation and the available resources for coping: a) the primary evaluation or perceived stress designates the manner that the subject identifies the situation and estimates his different characteristics; b) the secondary evaluation designates the stage where the subject estimates his personal and social resources or perceived control; c) the coping strategies. Objective. – Keeping in mind that gaining access to university is a potential stressful situation, we have studied, in light of transactional model of stress of Lazarus and Folkman the rule of cognitive variables (stress perceived, control perceived and stakes) and the adoption of functional coping strategies (problem solving, social support) or dysfunctional coping strategies (consumption of alcohol, medicine or other toxic substances, excessive sleeping, etc.) during the first two months of adaptation to university life. Population. – The subjects were students in the first year of psychology, that have twice completed five questionnaires in October (T1, N =110), then, in December (T2, N =119). Results. – A high or very high degree of stress was experienced by a quarter of the students and the global level of stress increased for 22,5% of students, decreases for 22,5% of them and does not change for 55% of students. The University seems stressful for a large number of students. The positive evaluations of challenge and benefit were significantly higher than the negative evaluations of threat and loss. The former are related to the stakes, which make up university success, whereas the later are linked to a perceived control. The positive evaluations decreased significantly whereas the negative evaluations increased during the two months of adaptation. Coping strategies. – The dysfunctional coping strategies were chosen by a significant number of students (35 to 45% over sleep as a mean of refuge, a quarter of students accept their situation passively, 16 to 17% of students consume alcohol, medicine or other toxic substances, and 13% behave auto or heteroaggressively). The positive evaluations of challenge and benefit seems to instigate functional coping strategies (planning, information''s research, self control strategies) whereas the negative evaluations of threat and loss lead to mobilization dysfunctional coping strategies like avoidance or escape (sleep, alcohol) and hetero aggressive confrontation. [Copyright &y& Elsevier]

Abstract: Benzodiazepines (BZD) dependence is frequent and induce withdrawal symptoms in high and low consumers, in both abrupt and taper discontinuations. Several withdrawal methods are described, involving either psychotherapy or pharmacotherapy. We have performed a multicenter, double-blind, randomised study comparing the efficacy and safety of lithium gluconate with that of a placebo in helping to achieve a complete and lasting BZD withdrawal. Outpatients receiving BZD since at least 6 months at a daily dose ranging from 10 to 40 mg diazepam or equivalent were eligible. Randomisation used a 3/2 design. This study consisted of four phases: a BZD stabilisation and randomly allocated placebo or lithium impregnation period of 4 weeks (D28 to D0) was followed by a 4-week BZD withdrawal period involving reduction of the initial dosage by 50% every week during 3 weeks (D0–D22) the third phase was an 8-week lithium maintenance phase (D28–D84) at the end of which the success of BZD withdrawal was assessed (primary aim). Finally, a 4-week lithium withdrawal phase D84–D112, where patients initially randomised to lithium were to randomly stop lithium either immediately or 2 weeks later, in order to assess a possible rebound effect due to lithium withdrawal. Lithium gluconate and placebo were dispensed in vials and were indistinguishable. Each verum vial contained 0.2796 mg lithium gluconate in 2 ml of isotonic glucose solution. Patients were to take three vials once a day. The main efficacy criterion was the rate of patients with a successful BZD withdrawal, defined as no BZD in urinalysis at D84 (or D98 for slow metabolisers) with no trial discontinuation due to anxiety, or due to withdrawal symptoms. Any other situation was considered as a failure. Secondary efficacy criteria included overall evaluation of treatment effect by both the investigator and the patient, and changes over time of COVI, HAMA and Physician''s Withdrawal Checklist (PWC) mean scores. Efficacy parameters were compared between verum and placebo overall and according to the initial dosage of BZD. Safety was assessed on all patients who took at least one dose of the study treatment. Success rates in BZD withdrawal were analysed using the Fisher''s exact test for the overall comparison and using the Cochran–Mantel–Haenszel (CMH) test for the comparison by initial BZD dosage. Changes over time in scores were analysed using non-parametric Wilcoxon–Mann–Whitney U tests for treatment effect comparison. Of 244 patients who entered the study, 146 were randomised to lithium gluconate and 98 to placebo. Eighty-six patients did not complete the study: 14 patients discontinued before the BZD withdrawal phase; 72 patients discontinued between BZD withdrawal and the end of the trial. The main reason for discontinuation was the recurrence of anxiety for 44 patients (22 in each group). Drop-out rates did not differ among treatment groups. All premature discontinuations were considered as failure. A total of 230 patients entered the BZD withdrawal phase and were taken into account for the ITT analyses, 136 patients allocated to lithium and 94 to placebo, of whom 32 presented a major protocol violation. Finally 198 patients were valid for the per-protocol analyses, 118 patients in the lithium group and 80 in the placebo one. There were no significant differences in demography and baseline characteristics among the two treatment groups. The overall success rates were high, over 60%, without significant difference between the two treatment groups. When considering the initial BZD daily dose, for patients taking 10 mg or less BZD, the success rates were still very high in both treatment groups without significant difference between them. There was too few patients doses over 20 mg/day to allow a relevant comparison. Nevertheless, for patients taking medium dosage, 11–20 mg/day, a difference of average 17.2% was observed between the two treatment groups in favour of the verum, without reaching statistical significance due to the size of this sub-group (lithium 61, placebo 38). The changes over time in anxiety scales (COVI, HAMA) and in withdrawal scales (Tyrer, PWC) did not allow to show any treatment effect, as expected with the observed low baseline scores. No effect of lithium withdrawal was reported. There was no rebound effect observed. The investigators assessed the safety of the products as ‘good’ or ‘very good’ for 95.7% of the patients allocated to lithium and 96.7% of those allocated to placebo. The success rates observed in the placebo group were unexpectedly high, over 60%, probably because of the intensive monitoring of the patients, leading to a difference between the two groups less important than expected and to an important lack of power of the trial. The main conclusion that can be drawn from this trial is the importance of a psychological help provided by the general practitioner. Nevertheless, the data suggested a positive effect of lithium gluconate in the BZD withdrawal, especially when taking into account the BZD initial dose: patients wishing to withdraw BZD and treated with BZD medium dosages seem to have better response when taking lithium in addition to the intensive monitoring, whereas in those treated with small BZD dosage are probably able to withdraw their treatment without drug therapy. There was not enough patients with high BZD initial dosage to draw any conclusion. [Copyright &y& Elsevier]

An introduction to the current issue is presented, discussing a variety of topics centered around the consumption of tranquilizing drugs in France, the highest in the World.