[Patients' burnout: evolution and prognosis in case of delayed support]. / Devenir et pronostic des patients en burn out pris en charge tardivement.

Patients' burn out : evolution and prognosis in case of delayed support. In France burn out can be considered as a medical and social scourge. In his late care, it is regularly associated with depression, post-traumatic stress, psychological and somatic burden and chronic diseases. The clinical aspects are complex based on its symptomatic diversity and causal heterogeneous factors. Patient's care is central and his/ her suffering should be recognized. The general practitioner needs to coordinate the treatment and drives a multidisciplinary team able to address the difficulty of the medical, social and administrative follow-up.

Devenir et pronostic des patients en burn out pris en charge tardivement. Aujourd'hui, en France, le burn out peut être considéré comme un fléau médical et social. Dans ses formes de prise en charge tardive, il se présente régulièrement sous les aspects cliniques de la dépression et du stress post-traumatique, accompagné de nombreux troubles psychologiques, somatiques et de maladies chroniques, tout en s'inscrivant dans le parcours professionnel d'un individu. Son tableau clinique est complexe en raison de sa diversité symptomatologique et de l'hétérogénéité des facteurs qui le déclenchent. Le patient doit être placé au centre du dispositif de soins et sa plainte reconnue. Le médecin traitant assure la coordination des soins et pilote une équipe pluridisciplinaire afin de gérer la difficulté du suivi médical, social et administratif.

Deficit of inhibition motor control in untreated patients with schizophrenia: further support from visually guided saccade paradigms.

In addition to classical delusional, negative, and cognitive deficit, schizophrenia has consistently been associated with impairments in saccadic eye movements, e.g., an increased error rate in the antisaccade task. We hypothesized that a deficit in inhibitory control is a core defect in untreated patients with schizophrenia leading to impairment in different oculomotor paradigms. Ten drug-free or drug-naïve patients with schizophrenia were matched in age and gender to 11 healthy controls with no psychoactive substance use or abuse. They were explored using reflexive saccades with unpredictable targets with or without the gap procedure, predictive saccades and a fixation/distracter paradigm. Patients with schizophrenia displayed shorter latency in reflexive and predictive saccades. In the GAP condition, patients made more anticipatory saccades, fewer regular saccades, and had a shorter latency of express saccades than controls. In addition, patients had an increased error rate in the fixation/distracters task. Altogether, these results provide new evidence of reduced prefrontal inhibitory regulation of subcortical and brainstem systems involved in the control of saccades.

Patient-based and clinician-based support for the remission criteria in schizophrenia.

This analysis characterizes patients with schizophrenia or schizoaffective disorder treated with risperidone who met remission criteria. In a 50-week, open-label trial, stable patients received long-acting injectable risperidone every 2 weeks. Remission criteria included severity (absent-mild ratings on core symptoms of the Positive and Negative Syndrome Scale) and duration (> or =6 months) components. The patients not remitted (severity component only) at baseline (n=394) are the subjects of this report. Measures applied included the PANSS, Clinical Global Impressions-Severity, patient-rated mental health status (Short Form-36), and Drug Attitude Inventory. Among patients who met remission criteria during the study (n=82), mean scores for all 30 PANSS items reflected absent-mild ratings at endpoint. The highest items represented an 'interpersonal' cluster, although mean ratings were still minimal to mild. Remitted patients experienced substantial improvements in Short Form-36 and Drug Attitude Inventory scores at endpoint. Although improvement occurred, it was less robust in patients who remained nonremitted (n=312). Logistic regression analysis found that remission (severity component only) was associated with a 97.1% probability of a 'not ill' rating on the Clinical Global Impressions-Severity. These remission criteria identified patients who differed from the nonremitted population on symptoms of psychopathology, medication attitude, health status, and overall clinical status, supporting the clinical validity of the remission criteria.

Effects of risperidone augmentation in patients with treatment-resistant depression: Results of open-label treatment followed by double-blind continuation.

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17< or =7 or CGI-S < or = 2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p = 0.05); relapse rates were 56.1 and 64.1%, respectively (p < or = 0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.

Ritanserin, a serotonin-2 receptor antagonist, improves ultradian sleep rhythmicity in young poor sleepers.

OBJECTIVES: To determine the effect on sleep electroencephalographic (EEG) activity of ritanserin, a serotonin-2 (5-HT2) receptor antagonist in young poor sleepers. METHODS: Eight male subjects underwent two randomized night studies after receiving either a placebo or 5 mg ritanserin administered in the morning. The overnight variations in the delta (0.5-4.0 Hz) and sigma (12.25-15.0 Hz) frequency bands were characterized using a peak analysis which provided a quantitative evaluation of the time-courses in EEG activity. RESULTS: In subjects under ritanserin, slow wave sleep duration and the number of non-rapid eye movement (NREM)-REM sleep cycles were significantly enhanced (P<0.01). The number of peaks in delta activity occurring in the normal 80-120 min range was significantly (P<0.05) increased. Using a delta peak analysis, 4 periods containing or not a significant peak were identified in each subject. A significant increase in delta activity was observed in the areas under the averaged curves during the second and the third periods (P<0.05), while sigma activity decreased under ritanserin during the first, second and third periods (P<0.05). CONCLUSIONS: These results demonstrate that ritanserin increases delta activity, possibly by opposing the inhibitory control of 5-HT2 receptor family. It restores sleep ultradian rhythmicity and improves sleep quality in young poor sleepers.

[A survey on the position of France in international clinical research as assessed by pharmaceutical laboratories]. / Attractivité de la France pour la recherche clinique internationale: une etude du Leem dresse un constat peu favorable et suggère des voies d'amélioration.

In order to evaluate the attractiveness of France for conducting international clinical trials, a survey was performed among pharmaceutical companies that are based in France or that have affiliates in France. The survey concerned international phase II and III clinical studies carried out in 2002 and 2003. Ten pharmaceutical companies representing 36% of the French market completed the survey. 134 trials were analysed in total. France recruited 8.3% of the overall number of patients recruited, and 15.0% of those recruited within Europe. France was within the overall mean with regard to the percentage of active centres (78.5% versus 79.5%) and the percentage of patients evaluable according to protocol (86.8% versus 87.3%). In contrast, France ranked within the last third of analysed countries with respect to the speed of recruitment (1.5 versus 1.9 patients/centre/month), and the number of queries per observation (16.8 versus 10.9). The analysis of the qualitative indicators of performance showed that, although the perception of pharmaceutical companies towards the quality of French medicine and administrative authorities is positive, France notably needs to improve the productivity of its clinical research in order to enhance its attractiveness for the pharmaceutical sponsors of clinical trials.

Symptom control, functioning, and hospitalization status in French patients changed from oral atypical antipsychotics to risperidone long-acting injectable.

Objective. To investigate efficacy and tolerability of risperidone long-acting injectable (RLAI) in French patients with schizophrenia or other psychotic disorders, who were all switching from previous treatment with oral atypical antipsychotics. The impact of treatment with RLAI on the hospitalization status of these patients was also examined. Methods. Clinically stable patients requiring a treatment change received 25 mg RLAI (increased to 37.5 or 50 mg if required) every 2 weeks for 6 months. Results. Of 130 patients (68.5% male, mean age 36.2 years), most (83.8%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were risperidone (80.8%), olanzapine (10.0%) and amisulpride (10.0%). Out of 66 patients hospitalized at baseline, 51 were outpatients at endpoint. Mean total PANSS, CGI-S and GAF scores were significantly reduced from baseline to treatment endpoint (p<0.001). Of those patients reported as moderate to severely ill at the beginning of the trial (81.3%), fewer had the same classification at endpoint (50.8%). Mean scores for total ESRS and Parkinsonism subscales were significantly reduced after only 1 month of treatment (p<0.001). Conclusion. Treatment with RLAI significantly improved disease symptoms, functioning, hospitalization status, and reduced movement disorders, in psychotic patients considered clinically stable on oral atypical antipsychotics.

Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4 years.

PURPOSE: To study the pharmacokinetics of topiramate (TPM) at steady state in children younger than 4 years comedicated with other antiepileptic drugs (AEDs). METHODS: Twenty-two children aged 6 months to 4 years with pharmacoresistant partial or generalized epilepsy were enrolled in an open-label prospective study. Children were assigned to different groups according to comedication with enzyme-inducing AEDs (n = 8), valproic acid (VPA) (n = 6), or other AEDs not known to affect drug metabolism (neutral AEDs, n = 7). One child was receiving treatment with both enzyme-inducing AEDs and VPA. After dose titration, blood samples were collected at steady state just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning dose of TPM. Pharmacokinetic parameters were determined by a noncompartmental method. RESULTS: TPM apparent oral clearance (CL/F) was significantly higher in children taking enzyme-inducing AEDs (85.4 +/- 34.0 ml/h/kg) than in those receiving VPA (49.6 +/- 13.6 ml/h/kg) or neutral AEDs (46.5 +/- 12.8 ml/h/kg). Conversely, dose-normalized areas under the plasma TPM concentration curves (0-12 h) were significantly lower in enzyme-induced patients than in patients receiving VPA or other AEDs. CONCLUSIONS: Compared with children not receiving enzyme inducers, children younger than 4 years who receive concomitant enzyme-inducing AEDs need higher doses (milligrams per kilogram) to achieve comparable plasma TPM concentrations.