Encephale
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This paper provides a review of safety and efficacy data as well as of pharmacological characteristics of atomoxetine, a new drug treatment for the Attention Deficit/Hyperactivity Disorder (ADHD). To date, the only pharmacological treatment available in France for children and adolescents diagnosed with ADHD is methylphenidate, a psychostimulant drug. However, the clinical response to methylphenidate may be absent or insufficient in about 20-30% drug-treated children while the occurrence of adverse effects with methylphenidate (sleep disturbances, loss of appetite, tics increase...) may sometimes require a dose reduction or even the discontinuation of the treatment. ⋯ A retrospective comparison showed that the adverse event profile of poor metabolizers was similar to that of extensive metabolizers. In summary, data presented suggest that atomoxetine is a safe and effective drug for the treatment of ADHD in children and adolescents. Further studies are expected to accurately define the place of atomoxetine in the treatment strategy of ADHD, a chronic and invalidating disorder affecting 3 to 7% of school-aged children.
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Imputability of thymic disorders caused by IFNalpha during the chronic Hepatitis C treatment -- hepatitis C and depression -- the infection by the hepatitis C virus (HCV) is a major public health concern since it affects 1.2% in the French population. Eighty percent of those contaminated by HCV keep bearing the virus chronically although they remain asymptomatic during many years. HCV infection is associated with psychiatric symptoms like depression. Together with other factors (eg the severity of hepatic condition), depression may induce significant impairment in quality of life. Conversely, some psychiatric conditions may increase the risk of HCV infection. In drug-addicted subjects using intravenous route, HCV contamination rate ranges from 74 to 100%. Compared with general population, a higher HCV contamination rate has also been noticed in some other subgroups of subjects (patients with alcohol abuse or dependence, with alcohol-induced hepatic disease and psychiatric inpatients). However, no valid explanation to this phenomenon has been established. Interferon alpha and depression - Interferons are a variety of cytokines naturally produced by human tissues and have also been synthesized for therapeutic purposes (treatment of a variety of cancers and viral infections). Many psychobehavioural symptoms are observed under IFNalpha treatment. Among them, mood disorders are known to occur early after entry into treatment and to be within the reach of preventive measures. The reported frequency of depression during IFNalpha treatment ranges from 0 to 37%. This variation reflects either methodological biases (eg differences in psychiatric assessment) or the heterogeneity of the population of patients accepted in therapeutic protocols. Note that the adjunction of ribavirine to IFNalpha in therapeutic protocols has not brought any changes in the depression frequency. The causal relationship between IFNalpha administration and the occurrence of mood disorders has been tackled by various recent research works focusing on the importance of the immune system in the pathophysiology of depression. Miscellaneous pathophysiological hypotheses -- nature of the psychobehavioural symptomatology -- in addition to depressive symptoms, IFNalpha treatment also induces various cognitive impairments and disruptions in EEG patterns. These symptoms are consistent with a mild subcortical dementia. Data resulting from pharmacological trials in humans and in animals are controversial (eg IFNalpha-induced symptoms being alleviated by both immune and antidepressant therapies). However, the debate about the nature of the psychobehavioural disorders observed under IFNalpha treatment might be no longer relevant in the light of recent theories which regard depression as a maladaptive response to a particular form of stress, namely a deep and diffuse feeling of sickness ("malaise"). These theoretical views ascribe the production of depressive symptoms to a disruption in the immune function, mediated by the variety of cytokines. The therapeutic effects of anti-depressive drugs are thus attributed to their analgesic properties, reducing the "malaise" feeling underlying depressive symptoms. Necessity of a second messanger -- accordingly to current pathophysiological theories, depression results from disorders of various CNS functions, mainly limbic, monaminergic and neuroendocrinal systems. Though, exogenous IFNalpha does not cross the blood-brain barrier when unscathed and an intermediary mechanism is necessary. First to be addressed is the cytokines system itself since it is composed of numerous different molecules interacting in an infinite number of possible combinations. Some of these cytokines (eg some interleukins) both are activated by IFNalpha and can reach CNS; they are good candidates for the role of second messenger mediating the induction of psychobehavioural disorders. Second, keeping in mind that serotonin is a monoaminergic neurotransmitter classically involved in depression pathophysiology, other works have demonstrated that IFNalpha modulates the peripheral activity of indolamine-dioxygenase -- a regulating enzyme of serotonin metabolism -- possibly through lymphocyte T CD4 activation. Third, other authors have postulated an immune-induced vagal mechanism to explain depression caused by IFNalpha. Action of IFNalpha on the neuroendocrine and on neuromodulating functions: monoaminergic hypothesis -- cytokines could have an influence on the mood through their modulating role on the serotoninergic system. IFNalpha treatment is reported to produce: 1) a decrease in tryptophan availability for serotonin synthesis, 2) a decrease in the 5-HIAA level in the LCR, and 3) a modification of the central serotoninergic receptors. Moreover, selective inhibitors of serotonin transporters are effective to treat or prevent depression caused by IFNalpha. Many studies support the serotonin-transporter hypothesis: in vitro, both IFNalpha and interleukine 4 (IL-4) increases the expression of serotonin transporter gene, IFNalpha increases in the production of IL-4 by mononucleus cells (not found in vivo). Serotoninergic system can also be altered by a peripheral action of IFNalpha on trytophan catabolism by activating a concurrent pathway (known as "kynurenine pathway") to serotonin synthesis. Finally, serotonin-mediated vulnerability to the psychobehavioural effects of IFNalpha could be underlain by a polymorphism of serotonin transporter gene. Concerning the other monoaminergic systems, IFNalpha seems to have an amphetamine-like effect at its first administration, followed by a decrease in dopaminergic tone with chronic administration. Dopaminergic depletion, subsequent to psychostimulant abuse for instance, results in severe depressive syndromes. Interactions between IFNalpha and noradrenergic system have also been reported. Neuroendocrinian hypothesis -- when administered through central or peripheral way, IFNalpha simulates/inhibits the corticotrope axis and alters endorphin system as shown by the induction of analgesia, catatonia and behavioural slowdown that can be suppressed by opioid antagonists. IFNalpha neurotoxic effects are successfully treated by naltrexone. Lastly, IFNalpha is known to cause disorders in thyroid function that are likely to contribute to the production or aggravation of mood disorders. ⋯ A better understanding of pathophysiologic mechanisms underlying psychiatric side-effects of IFNalpha is essential to extend access to treatment to some categories of patients that remain excluded from the protocols. A better management of those psychiatric side effects should help the clinician not to draw aside patients at risk, ie patients with depression, drug and alcohol addiction. Treating them in a pragmatic and careful way is a major issue, since this population represents a high percentage of the potential candidates for interferon therapy.
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Previous studies on schizophrenia have suggested that context-processing disturbances were one of the core cognitive deficits present in schizophrenia. Schizophrenic patients have a failure either of inhibition strategy and maintenance of visuospatial information (25) in condition of contextual interference. In the present study, we explored the performances of untreated schizophrenic patients with 2 tasks exploring detection and long term retention of complex visual features and field dependence-independence tasks were selected. These abilities involve temporary maintenance of visuospatial information and executive functioning of visual working memory system. Several studies have shown that cognitive deficit may depend on schizophrenic symptomatology. However results remain controversial in determining the specific influence of negative and positive symptomatologies as well as clinical disorganization. Our goal was to explore the processing of spatial context and its relation to disorganized syndrome. This study was approved by the local ethic committee. ⋯ The severity of disorganization influences the visuospatial context processing and visuospatial working memory. These results show the heterogeneity of cognitive functioning regarding to schizophrenic symptomatologies. This difficulty could be related to a problem of central executive functioning in the visuospatial component of working memory, possibly mediated by the dysfunction of dorsolateral prefrontal cortex.
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Multicenter Study
[Psychotropic drug use and mental psychiatric disorders in France; results of the general population ESEMeD/MHEDEA 2000 epidemiological study].
The use of psychotropic drugs is high in France and has increased over the last two decades. To date, no national study evaluating psychotropic drug use in the context of the diagnosis of psychiatric disorders has been performed. Such data has now been generated in the ESEMeD/MHEDEA 2000 study, which has allowed comparison of the situation in France with that in five other European countries (Germany, Belgium, Spain, the Netherlands and Italy). ⋯ Over the last two decades, use of AX-HY seems to have decreased in France, even though it remains higher than that observed in the other European countries participating in this study. This high use can be explained in part by the observation that, in around half the cases, it corresponds to occasional use. In contrast, the use of antidepressants has increased. In subjects with recent mood disorders or anxiety disorders, the use of AX-HY remains higher than that of antidepressants. Finally among users of AX-HY, only half of them had presented a mood disorder, anxiety disorder or alcohol use disorder during their lifetime, whereas this proportion rose to 80% for users of antidepressants.
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Schizophrenia is a disease affecting the young adults and amounts to approximately 300,000 people in France. The French public psychiatric sector takes care of approximately 150,000 adults schizophrenics: 50% benefit from ambulatory care, 50% are in partial or full-time hospitalization care. Schizophrenia represents the first diagnosis that psychiatric sectors take in charge. The costs associated with schizophrenia, mainly hospital costs, are important and were estimated at 2% of the total medical costs in France. In the French social welfare system, the social costs (pensions, allowances, managements of custody or guardianship by social workers) are also to be taken into account: it amounts to a third of the global direct cost. Schizophrenia also generates indirect costs (losses of productivity and premature deaths) which would be at least equal, or even more important, than direct medical costs. The non-compliance to the antipsychotic treatment is a major problem with people suffering from schizophrenia. Indeed the lack of compliance to the treatment, estimated at 20 to 40%, is a major handicap for schizophrenic patient stabilization. The poor level of compliance is due to many various causes: adverse effects that are considered unbearable, medicine viewed as persecutory, negation of the disease, nostalgia for the productive phases of the disease, lack of social support, complexity of the prescription, relapse itself. Compliance is thus influenced by the patient's clinical features, local provision of health care and the specific nature of the drug (adverse effects, pharmaceutical formulation). The atypical antipsychotics present fewer extrapyramidal side effects and reduce the cognitive deficits associated with the disease, which results in improved compliance. Long-acting injectable antipsychotics allow a better therapeutic compliance and thus better efficacy of the treatment. Several studies have shown a significant improvement in compliance related to the pharmaceutical formulation of antipsychotics. Hospitalization and relapse risks are lower in compliant than in non-compliant patients. ⋯ The schizophrenia is a relatively frequent disease. (ABSTRACT TRUNCATED)