Search

L'Encephale - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le mardi 17 mai 2016

AIn this work, the authors have analysed the principal studies on the interest in the use of benzodiazepines in schizophrenia. The first double-controlled study concerning this question was conducted in 1961. The results of the first studies are criticisable due to the variability of the diagnostic and clinical assessment criteria, as well as to the divergences between the different conclusions. Through this review of literature, the authors wish to clarify the questions and hypothesis raised specify certain therapeutic strategies. MECHANISM OF GABA-ERGIC TREATMENTS: The analysis of the principle works on this question provides evidence on the use of benzodiazepines in schizophrenia. By fixing on their receptors, benzodiazepines facilitate GABA-ergic transmission. GABA is an inhibitor neurotransmitter. The GABA stimulation induced by benzodiazepines may be at the origin of a reduction of the pre-synaptic release of dopamine in the mesolimbic region. The GABA stimulation may also delay the post-synaptic adaptation of the dopaminergic neurons to neuroleptics. This phenomenon may enhance the activity of neuroleptics in resistant schizophrenia. Benzodiazepines would also have an effect on the mesoprefrontocortical regions where neuroleptics may be less efficient. It is interesting to note that this cerebral region is particularly sensitive to stress. This effect of benzodiazepines on the mesoprefrontocortical region might explain a preferentially beneficial effect in patients who have radiographic signs consistent with prefroncortical atrophy, although this observation remains preliminary. BENZODIAZEPINES IN MONOTHERAPY: In monotherapy their action on productive and deficient psychotic symptoms is greatly discussed and not very convincing. The main studies in the use of benzodiazepines alone ) are heterogeneous for their diagnosis criteria, their methodology and their results. The conclusions of the publications are not totally clear, and different points are to be criticized: heterogeneity of assessment criteria, heterogeneity and variability of methodology, use of non standardized scales, most of the studies are open studies, variability of benzodiazepines dose. BENZODIAZEPINES IN ASSOCIATION WITH NEUROLEPTICS: In few controlled studies, most authors have underlined ) the advantage of the association of benzodiazepines with neuroleptics. This association may act either on positive symptoms (hallucinations, delusions) or on negative symptoms. The latent period and the length of the effect of benzodiazepines in the treatment of psychotic patients remain unclear. According to certain studies, the therapeutic effect may appear in a short time, and then disappear within the fourth week. The association of benzodiazepines with neuroleptics is particularly helpful for patients with great anxiety, whether they have neuroleptic intolerance or not. There is no robust convergence about the type of benzodiazepines and their optimal dose in the treatment of schizophrenia. Their use may permit a reduction in the neuroleptic dose. They could increase the plasma concentration of neuroleptics and they might act on the mesoprefrontocortical regions where there are fewer dopaminergic auto receptors. BENZODIAZEPINES AND ANXIETY IN SCHIZOPHRENIA: States of anxiety, and in particular panic disorders that would participate in the exacerbation of psychotic symptoms, would benefit from the use of benzodiazepines. Anxiety can be considered as a major symptom of schizophrenia: insecure feelings and impressions of threatening events are frequent during schizophrenia. Interpretations or brutal hallucinations can lead to the feeling of imminent catastrophe or anxiety. Nevertheless, anxious phenomenons are under-estimated for many reasons: on the one hand, positive symptoms may hide anxiety, and on the other, the symptoms that are observed in patients treated with neuroleptics are often attributed to the neuroleptic side effects rather than linked to anxiety. Benzodiazepines and catatonia - Lorazepam has demonstrated its efficacy on catatonia. This effect seems to be specific of small doses of lorazepam (

Avant de repondre, je voudrais dire que l’on m’a souvent renvoye le fait qu’il fallait etre « original » pour s’interesser a la personne âgee, lorsque l’on est psychiatre. On sait bien que la psychiatrie s’est longtemps desinteressee des troubles mentaux de la personne âgee. Cette question reflete assez bien mon propre questionnement sur cette thematique et mon implication dans la mise en place des Journees du vieillissement. Je vous propose plusieurs perspectives avant de debattre

The neuropeptide oxytocin (OT) is an evolutionary highly conserved molecule that plays a part in the regulation of complex social cognition and behaviours. From a pathophysiological point of view, several studies have evidenced dysfunctions of the oxytocinergic system in autism spectrum disorders (ASD): a lowering of plasma OT and genetic or epigenetic anomalies of the OT receptor. Therefore, some authors have hypothesized that an abnormality in the OT neurotransmission may account for several features of autism and that a treatment restoring a normal OT pathway functioning could improve social abilities. OT administration has thus been used in clinical trials, especially in groups of subjects suffering from autism. Some studies found that OT decreased repetitive behaviours, enhanced emotional understanding of speech intonation, improved performance of the Reading the Mind in the Eyes Test and reinforced cooperation. Nevertheless, the findings of the OT administration studies on clinical samples show great diversity. The context, the personality and childhood experiences of the subject could be moderators influencing the effect of exogenous OT. Besides, three mechanisms could play a part in the action of OT on ASD social symptoms: anxiety reduction (with a lowering in the hypothalamic-pituitary-adrenal axis responsiveness and in the amygdale reactivity to social stimuli), increased affiliative motivation (involving the dopaminergic pathway and several regions of the social brain) and enhanced perceptual selectivity and social stimuli salience. To conclude, OT could be a promising molecule used as a treatment to promote social behaviours, helping individuals with ASD to develop new relationships. OT could be administered during a cognitive-behavioural therapy to reinforce the efficacy of such procedures. More studies are needed, on larger samples, to investigate the safety and efficacy of OT administration and to specify optimal dosages and characteristics of patients who may benefit from this treatment.

In recent years, discovery of ketamine's fast and powerful antidepressant effects for treatment-resistant depression (TRD) has led to rethinking of the pathophysiology of depression. Numerous studies in humans and animals have focused on mechanisms of action underlying this effect, producing a number of explanatory pathways.The aim of this article is to summarize the various hypotheses underlying rapid antidepressant action of ketamine and therefore to better understand the mechanisms underlying depression and antidepressant action.Ketamine unique antidepressant properties have led to many studies on its neurobiological grounds. Intracellular signaling pathways such as mTOR, GSK3 or eEF2 seem to play a key role and are associated with an increased synaptic plasticity. Other hypotheses are discussed such as ketamine effects on neuro-inflammation, the role of anterior cingulate cortex in brain changes induced by ketamine, and the potential benefits of analgesic properties of ketamine in depressive disorders.Our review highlights the potential role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Understanding which pathways underlie the fast antidepressant effect of ketamine paves the way for the development of new antidepressants.

Depressive disorders have a major impact on public health. They are prevalent and disabling, with high economic burden for society. Antidepressants have a delayed action and at least one third of patients do not achieve adequate response. The recent discovery of ketamine's unique antidepressant properties, with rapid onset of response and high rate of responders opens new perspectives for treatment-resistant depression (TRD).The aim of this article is to summarize preclinical trials and clinical trials demonstrating ketamine antidepressant properties and to review the different modalities of use.Most clinical studies used ketamine with a single subanesthetic intravenous administration in patients with treatment-resistant depression, demonstrating a rapid but transient antidepressant response with high response rates. To prevent relapse and maintain the initial benefits, few studies have shown the interest of serial infusions of ketamine, while others combined ketamine and electroconvulsive therapy using the former as an anesthetic. So far, relay treatments with glutamatergic agents such as riluzole are disappointing. Although most studies were conducted in patients with TRD in recurrent depression or bipolar disorder, efficacy in acutely suicidal patients is promising.Our review highlights the increasing interest in the use of ketamine in the treatment of treatment-resistant depression. Although a widespread use of ketamine as an antidepressant in routine clinical settings seems limited by psychotomimetic effects and the lack of strategy to maintain initial benefits, ketamine or related drugs might be used to target specific conditions, such as bipolar depression or high suicide risk.

Conversion disorder refers to the occurrence of neurological-like symptoms or deficits that are neither intentionally produced nor simulated. While it cannot be explained by an organic disease, it is often related to psychological events.We report the case of a 33-year-old patient with a fluctuating hysterical tetraplegia, which had started three years earlier. After the failure or the exhaustion of several biological (psychotropic medication, transcranial magnetic stimulation) and psychotherapeutic strategies, treatment with electroconvulsive therapy (ECT) was conducted. A total of thirty-five ECT sessions were performed. Whereas the patient's clinical state was initially characterized by a complete quadriplegia and an uncontrollable muscular hypertonia, we noted that the ECT sessions were associated with a slow, though remarkable, progress. At first, the sessions were followed by moments of altered consciousness during which the patient would be relaxed and could make simple movements. Secondarily, not only was our patient able to consciously move his four limbs, but he was also able to walk. However, those improvements remained partial and fluctuating, sometimes allowing the symptom to return temporarily secondary to frustrations or annoyances. Finally, our patient relapsed. Nevertheless, his clinical state presently remains better than that in which we first knew him.The treatment of conversion disorders has been the subject of few studies and predominantly remains symptomatic. Its main goals are: to lessen secondary gains impact by adopting a neutral behaviour towards the symptom and by encouraging physical rehabilitation; to lower the symptom by allowing the patient to understand the normal functioning of the diseased organ, and; to help the patient to deal with stressful situations. There is no evidence that hypnosis is superior to medical and other psychotherapeutic approaches. Pharmacological treatments may be helpful in the case of anxiety, impulsivity or depression, albeit delivered with caution. According to some case reports, transcranial magnetic stimulation has also been associated with clinical remission. Although the use of ECT in motor conversion disorders constitutes an uncommon procedure, and even if no clinical trial has evaluated its impact on such a pathological condition, several case reports suggest that electroconvulsive therapy can be efficient in the treatment of motor conversion disorders. This efficacy may rely on several hypotheses. ECT could induce neural modifications, and participate in the suppression of an active inhibition, which is responsible for hysterical symptoms. Indeed, conversion cerebral disorder correlates can be explored with the help of functional neuro-imaging techniques, which could therefore also identify ECT neural effects. ECT adverse effects on memory could lead to a new relationship with the symptom, and modulate the psychological conflict which has participated in its emergence. Narcoanalysis, ECT sessions could have an impact on consciousness by means of some dissolution and reorganization phenomenon. It could therefore participate in the ending of an emotional block, the psychic integration of traumatic events and the recovery of a voluntary motor control. Finally, ECT could be efficient thanks to its antidepressant properties, especially its ability to stimulate triaminergic, and particularly dopaminergic transmission. This case report reminds us how difficult it can be to deal with severe conversion disorders, and to navigate between two reefs, which are abstention, and therapeutic escalation.

Maintenance electroconvulsive therapy (M-ECT) is a treatment indicated for the treatment and prevention of recurrent depression in patients who either do not respond or do not tolerate psychotropic medication. We evaluated, retrospectively, clinical response to a 6-month minimum course of M-ECT in 25 patients with a diagnosis of bipolar disorder or schizoaffective disorder according to DSM IV-TR criterion. Our study demonstrated a significant improvement of Global Assessment of functioning (GAF) scores after a six month minimum course of M-ECT (34.8 ± 12.6 vs 65.6 ± 10.8; P0.05) as well as Brief Psychiatric Rating Scale scores (BPRS): 79.3 ± 12.4 vs 43.4 ± 10.2; P0.05). We observed a slight increase of Mini Mental State Examination (MMSE) scores after M-ECT; nonetheless, it was not statistically significant (24.2 ± 2.4 vs 26.2 ± 2.4; P=0.2). Regarding the mean duration of hospitalizations, we showed a statistically significant decrease in the median number of days of hospitalization (72 [59-93.50] days before M-ECT vs 43 [25-76] days since the first M-ECT; P=0.017). Maintenance ECT allowed a significant improvement in psychiatric symptoms and global functioning of the patients included in this study, as well as a decrease in the number of days of hospitalization. However, our pattern is limited because of its small size; so, further prospective studies in this field, including larger population is highly recommended.

"Depression" and "old age" are often associated among our contemporaries. In this case, "depression" is understood to be "existential despair" and not a "depressive disease": an amalgam is made of the tragedy of the patient's existence and a pathological condition. Clinical pictures of depression, the pathological nature of which is obvious, are frequent in the elderly; however, the line between normal and pathological becomes less clear above a certain symptomatic threshold, in the presence of chronic evolutions and in situations of comorbidity. The nosographical tool, in spite of its limits, is precious. Epidemiological studies that include the comorbidities of the depressive episode with cognitive and/or somatic affections permit better estimations of the prevalence of the symptoms and the depressive problems among elderly populations. The formula "depression is depression at whatever age" harbours a certain truth if one takes into account the multiple factors that modify the symptomatic expression of depression in later life. The most documented factor is the comorbidity of depression with somatic affections that is present in the majority of those aged over 80. Other psychological or sociocultural factors are also apparent, but their influence has been studied less. The decline in cognitive performance observed during depression is not exclusive to the elderly but is undeniably more marked in this population. Making an early diagnosis of Alzheimer's disease or, conversely, eliminating this diagnosis in a depressed patient complaining of diminished cognition is an essential step in the subsequent management. Together with the neuropsychological assessment and brain imaging, required for diagnosis, a neuropsychogeriatric pluridisciplinary assessment is obviously required. The management of geriatric depression is based on various approaches that include somatic care, psychotropic drugs, brain stimulation techniques and psychotherapy, but also requires medicosocial care. The coordination of care is incumbent on the general practitioner in the heart of the plan. However, this theoretical mission may appear impossible for the management of complex cases. Based on this, reflections on were initiated on the modalities of adapting the Anglo-Saxon "collaborative care" to France: coordination of the various therapeutic interventions by a care manager would offer greater efficacy than that of the usual care modalities.

AIn this work, the authors have analysed the principal studies on the interest in the use of benzodiazepines in schizophrenia. The first double-controlled study concerning this question was conducted in 1961. The results of the first studies are criticisable due to the variability of the diagnostic and clinical assessment criteria, as well as to the divergences between the different conclusions. Through this review of literature, the authors wish to clarify the questions and hypothesis raised specify certain therapeutic strategies. MECHANISM OF GABA-ERGIC TREATMENTS: The analysis of the principle works on this question provides evidence on the use of benzodiazepines in schizophrenia. By fixing on their receptors, benzodiazepines facilitate GABA-ergic transmission. GABA is an inhibitor neurotransmitter. The GABA stimulation induced by benzodiazepines may be at the origin of a reduction of the pre-synaptic release of dopamine in the mesolimbic region. The GABA stimulation may also delay the post-synaptic adaptation of the dopaminergic neurons to neuroleptics. This phenomenon may enhance the activity of neuroleptics in resistant schizophrenia. Benzodiazepines would also have an effect on the mesoprefrontocortical regions where neuroleptics may be less efficient. It is interesting to note that this cerebral region is particularly sensitive to stress. This effect of benzodiazepines on the mesoprefrontocortical region might explain a preferentially beneficial effect in patients who have radiographic signs consistent with prefroncortical atrophy, although this observation remains preliminary. BENZODIAZEPINES IN MONOTHERAPY: In monotherapy their action on productive and deficient psychotic symptoms is greatly discussed and not very convincing. The main studies in the use of benzodiazepines alone ) are heterogeneous for their diagnosis criteria, their methodology and their results. The conclusions of the publications are not totally clear, and different points are to be criticized: heterogeneity of assessment criteria, heterogeneity and variability of methodology, use of non standardized scales, most of the studies are open studies, variability of benzodiazepines dose. BENZODIAZEPINES IN ASSOCIATION WITH NEUROLEPTICS: In few controlled studies, most authors have underlined ) the advantage of the association of benzodiazepines with neuroleptics. This association may act either on positive symptoms (hallucinations, delusions) or on negative symptoms. The latent period and the length of the effect of benzodiazepines in the treatment of psychotic patients remain unclear. According to certain studies, the therapeutic effect may appear in a short time, and then disappear within the fourth week. The association of benzodiazepines with neuroleptics is particularly helpful for patients with great anxiety, whether they have neuroleptic intolerance or not. There is no robust convergence about the type of benzodiazepines and their optimal dose in the treatment of schizophrenia. Their use may permit a reduction in the neuroleptic dose. They could increase the plasma concentration of neuroleptics and they might act on the mesoprefrontocortical regions where there are fewer dopaminergic auto receptors. BENZODIAZEPINES AND ANXIETY IN SCHIZOPHRENIA: States of anxiety, and in particular panic disorders that would participate in the exacerbation of psychotic symptoms, would benefit from the use of benzodiazepines. Anxiety can be considered as a major symptom of schizophrenia: insecure feelings and impressions of threatening events are frequent during schizophrenia. Interpretations or brutal hallucinations can lead to the feeling of imminent catastrophe or anxiety. Nevertheless, anxious phenomenons are under-estimated for many reasons: on the one hand, positive symptoms may hide anxiety, and on the other, the symptoms that are observed in patients treated with neuroleptics are often attributed to the neuroleptic side effects rather than linked to anxiety. Benzodiazepines and catatonia - Lorazepam has demonstrated its efficacy on catatonia. This effect seems to be specific of small doses of lorazepam (5 mg/day). It should be compared to the effect of zolpidem in the same conditions. This prescription should be limited to acute catatonia, with no effect on chronic catatonia. Benzodiazepines and neuroleptic side effects - The use of benzodiazepines to treat some side effects of neuroleptics such as akathesia is reported by certain authors but remains little explained. They may have no effect or only small effects on tardive dyskinesia, but could reduce their incidence with the use of the smallest doses of neuroleptics in association with benzodiazepines. Safety of use - The safety of use of benzodiazepines in schizophrenia, particularly in association with neuroleptics is admitted, however recommended precautions with clozapine are to be noted. Benzodiazepine combined with clozapine clearly increases the frequency of cardiovascular and respiratory accidents. Some studies point out the risk of behavioural desinhibition and dysphoria. Their use should also be limited to patients with good compliancy, in order to avoid exacerbation of symptoms in the case of brutal interruption of the treatment. Dependency, which is an important issue in the use of benzodiazepines, seems much lesser in schizophrenia than in personality disorders and anxiety. Conversely, some studies point out the benefits of benzodiazepine use in schizophrenia, with their efficacy in the treatment and prevention of drug abuse. Finally, benzodiazepines contribute to the establishment of a good patient-doctor relationship, and may guarantee enhanced treatment compliancy.

Electroconvulsive therapy, a standard treatment in mood disorders, is sometimes also indicated in psychotic disorders, especially in the treatment of refractory schizophrenia. In this instance, maintenance electroconvulsive therapy (M-ECT) can also become a long-term treatment. This paper presents the effects of M-ECT in the treatment of refractory schizophrenia using a retrospective analysis. Previous works showed that electroconvulsive therapy is effective on catatonia, anxiety with somatisation, lack of compliance, opposition, delusions especially with hallucinations and persecution, anorexia, agitation, carelessness, aggressive behaviour and moral pain. It is ineffective on bewilderment, somatic complaints and negative symptoms.A retrospective analysis of a clinical cohort of patients treated with M-ECT was carried out to determine the specific indications of M-ECT, its effectiveness on clinical symptoms, quality of life, relapse rates and use of medication. Nineteen patients with DSM-IV diagnosis of paranoid schizophrenia (n=5), schizophrenia with neurotic symptoms (n=3), disorganized schizophrenia (n=1), hebephrenia (n=3) and schizoaffective disorder (n=8), treated in the department of the University Hospital of Sainte-Anne in Paris, received M-ECT between 1991 and 2005. Seven patients are still under this treatment. Their mean age at the beginning of treatment was 47.5 years with a mean duration of the illness of 24 years. The indication of M-ECT was the increase of acute episodes, an increase of symptoms intensity, the inefficiency or intolerance to pharmacological treatments or an early relapse after ECT discontinuation. All patients had previously been successfully treated by ECT during an acute episode. Each patient received an average of 47 bilateral M-ECT under general anaesthesia at one to five weeks' intervals for a mean period of 43 months. All of them were also treated by antipsychotics; in addition, 30% received mood stabilizers and 10% antidepressants. The dosage of antidepressants and mood stabilizers was reduced during M-ECT treatment, especially in patients with schizoaffective disorder, probably in relation with the effectiveness of ECT on mood symptoms.During M-ECT, the mean duration of yearly hospitalizations was decreased by 80% and the mean duration of each hospitalization by 40% with a better ability to take part in activities, sometimes even to return home or go back to work. There was also a positive effect on quality of life considering the severity of symptoms and the long psychiatric history of these patients. The possibility to go from a full time hospitalization to a day-care facility or to live in a halfway house can be considered as a huge progress. M-ECT was efficient on mood symptoms, delusions, anorexia, suicidal impetus, anxiety symptoms and increased cooperation and treatment compliance. Efficacy on obsessive compulsive symptoms was less obvious. There was no effect on dissociation and negative symptoms. Relapses essentially occurred after a stressful life event, a too long interval between the M-ECT sessions or, in 50% of the cases, without any obvious etiology. It required a revision of the M-ECT program and, most of the time, an hospitalization for full ECT treatment.There is no consensus on the rate and number of M-ECT as it varies from patient to patient and depends upon the extent of the clinical response and side effects. The discontinuation of M-ECT will depend on the clinical symptoms, compliance and tolerance to ECT. As it is the case with ECT treatment for an acute episode, available evidence suggests that treatment with antipsychotics should continue during the maintenance ECT course.Maintenance electroconvulsive therapy combined with medication may be an efficient alternative to pharmacological treatment alone in refractory schizophrenia. Alternative therapeutical strategies are crucial in this domain, due to the important public health problem it raises. There are few randomised prospective controlled clinical trials regarding this treatment and further clinical investigations are necessary, notably to define standardized criteria for M-ECT programs.

Folie à deux or induced delusional disorder is a rare mental disorder. It was initially described by the French Lasègue and Falret in 1877. Two subjects, who live in a close relationship, in isolation, share delusional ideas based on the same themes. Various classifications exist. Its epidemiology remains unclear, because most of the data have been extrapolated from case reports.In this paper, we describe and comment two cases of shared paranoid disorder: in the first case report, a husband shares the paranoiac delusion of his wife; the second case report describes a shared paranoid disorder between a schizophrenic daughter and her mother.A review of the existing literature is also presented. Some clinical characteristics arise, such as frequent mother-daughter associations and diagnosis of schizophrenia in inducing subject. Particular social and psychopathological conditions for the occurrence of a shared delusional disorder are described, such as personality traits and genetic influences. This article also reviews some forensic issues, which may be of importance, since this disorder is underdiagnosed. Data concerning the principles of its treatment are sparse, but most authors consider that the separation of the two subjects has to be the basis of any intervention. The inducing subject has to be treated with specific medical interventions, including the prescription of antipsychotics. Sometimes, the separation is enough to eliminate the delusional ideas from the induced subject, who, according to the ICD-10 and DSM-IV, is the only one to meet the criteria for shared delusional disorder. The case reports are discussed in light of the review, and some propositions for their treatment are made.As shared delusional disorder is a rare disease, only few data exist on its pathophysiology and mechanisms, and controlled studies are needed in order to understand its specific implications better and to define recommendations for its management.

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.Thirty-six schizophrenic patients were included according to DSM IV criteria (19 neuroleptic naïve, 17 unmedicated patients during more than 3 months). Thirty-six healthy controls were matched to patients for age, gender and level of education. Absence of axis 1 pathology was attested for controls with SCID-NP. Current symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) (14). Clinical disorganisation was evaluated with the disorganisation score established upon a factorial analysis of PANSS by Lepine and Lançon. Items selected to distinguish the disorganised group were abstraction, disorganization, orientation, and attention.Two tasks of embedded figures were administered individually to patients and controls. The Faverge task (Research of Figures-RF) (10) evaluates the ability to recognize the target from spatial complex geometrical figures. The Group Embedded Figure Task (GEFT - Oltman) assesses the detection and maintenance of visual target and its recognition within a complex figure. Performance between patients and controls were compared with the Student T test. The comparison of two clinical subgroups of disorganized and low disorganized patients and control group was performed with an ANOVA. Tuckey test was used for pairwise comparisons.We defined two subgroups of patients, disorganized patients (subscore 12, n=17) and low disorganized patients (subscore12, n=19). Theses 2 subgroups were similar for age and level of education. Concerning the two tasks, there was no significant difference between schizophrenic patients and normal controls. The comparison between subgroups of disorganized and low disorganized patients, for RF task, showed a decrease of correct answers with disorganized patients (p0.05). For GEFT task, disorganized patients had a decrease of correct answers p0.01) and more errors (p0.01) and omissions (p0.05). The low disorganized patients exhibited for the two tests comparable performance to controls. The disorganized patients had a decrease of right answers (p0.05) and more errors (p0.05) than controls for GEFT task and no significant difference for RF. However, with IQ (evaluated with an abstract reasoning test) introduced as covariate, only correct answers for GEFT task remain significant (p0.05).The weak performance of disorganized schizophrenic patients for two tasks RF and GEFT showed that treatment of visuospatial information was impaired in the first perceptive phase of selection and in the organization of information (RF), especially with the maintenance of visual information in memory (GEFT). By contrast, low disorganized patients demonstrated a correct analytic treatment of elementary processing and visuospatial working memory.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.

Conventional and atypical antipsychotics are known to induce weight gain, cause glucose and lipid impairments among schizophrenic patients. These impairments contribute to the intrinsic risk factors linked to the psychiatric pathology (sedentary state, nicotin addiction, diabetes) increasing numbers of cardiovascular complications. We propose to study ponderal modifications and presence of metabolic abnormalities in a population of schizophrenic patients treated by conventional or atypical antipsychotics, depending on the received treatment; 32 patients, whose schizophrenia diagnosis had been previously made, were consecutively included over a 4 months period. They were divided into three groups: patients treated by conventional antipsychotics (n = 6), by atypical antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%) display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4 other patients (12.5%) have hypercholesterolemia. No particular drug could be directly targeted, partly because of the restricted size of our sample, but the patients presenting metabolism impairment were treated by atypical antipsychotic. The observance of these abnormalities is reflected in publications and lead to some antipsychotic treatments monitoring rules.

The hypothesis for a neurodevelopmental basis to the underlying physiopathological disorder leading to schizophrenia has been proposed by many investigators for more than two decades. This hypothesis is supported by -several lines of evidence. Pregnancy and delivery complications, particularly those with known or presumed impact on fetal neurologic development, result in increased risk for psychotic disorders. Other possible etiologic candidates include viral infections. Minor physical anomalies, manifesting as slight anatomical defects of the head, hair, eyes, mouth, hands and feet, as dematoglyphic fluctuating asymmetries, are due to some injury occurring during the first or second trimester of fetal life, and are more common among patients with schizophrenia and in their unaffected siblings than in the general population. But a major Issue in a such neurodevelopmental model theory is the delayed onset of the schizophrenic disorder. Although early signs and prodromal symptoms can be defined retrospectively in patients who have developed schizophrenia, they do have to be confirmed as early predictors in prospective and longitudinal studies. Abnormalities in brain development and maturation seem to begin prenatally, but may continue throughout childhood and the observed changes during these periods must have -consequences for the neuronal circuitry and connectivity. Advances in brain imaging have now led to the identification of a great number of brain abnormalities in schizophrenia. The most consistently replicated structural anomaly present in the brains of patients with chronic schizophrenia is ventricular enlargement. These findings also include medial temporal lobe structures (which include the amygdala, hippocampus, and parahippocampal gyrus), and neocortical temporal lobe regions (superior temporal gyrus). There is also some evidence for frontal lobe abnormalities, particularly prefrontal gray matter and orbitofrontal regions. Similarly, there are findings for parietal lobe abnormalities (particularly of the inferior parietal lobule which includes both supramarginal and angular gyri) and subcortical abnormalities (basal ganglia, corpus callosum, and thalamus) but more equivocal evidence for cerebellar abnormalities. However, it is possible that the brain structural abnormalities observed in schizophrenia are not only due to neurodevelopmental anomalies, but also to an alteration in cortical plasticity and maturation processes that occurs over the long course of the disease. The genetic predisposition for schizophrenia has been confirmed in many studies. It is utterly disappointing that molecular genetic approaches have so far not yielded conclusive evidence for vulnerability or protection genes in schizophrenia. Future studies will likely benefit from: 1) studying more homogeneous patient groups, 2) studying high risk populations such as biological relatives of patients with schizophrenia, 3) using longitudinal and prospective methodological design in order to confirm the predictive validity of neurodevelopmental clues found in patients with schizophrenia, 4) applying newer strategies such as composite phenotypes of developmental origin, in combination with new genetic methods.

Alzheimer's disease has definitively emerged from its ghetto and has been identified as a (priority) public health concern in view of the increasing age of the population. Considerable advances have been made in this disease over the last 15 Years, with progress in the following fields: knowledge of the underlying aetiopathogenetic, genetic and biochemical mechanisms; semiological, clinical and paraclinical approaches; creation of early diagnostic centres and multidisciplinary care networks; therapy available to patients or currently under development. The four existing acetylcholinesterase inhibitors having confirmed symptomatic action in patients with mild to moderate Alzheimer's disease have now been joined by memantine (Ebixa), a non-competitive agonist of N-methyl-D-aspartate (NMDA) receptors. One pathogenic mechanism of Alzheimer's disease appears to be hyperactivity of the glutaminergic neurons. Various preclinical studies have shown that memantine (Ebixa) inhibits glutaminergic hyperactivity in Alzheimer's disease through modulation of NMDA receptors. Since the early 1990s, several controlled clinical trials in patients with moderate to severe Alzheimer's disease (3MMSEor =14) have demonstrated the efficacy of memantine on cognitive criteria (cognitive evaluation of severe dementia) (Severe Impairment Battery--SIB), functional criteria (Functional Assessment Stage--FAST) and global clinical criteria (Clinician's Interview-Based Impression of Change--CIBIC-Plus). The data from these studies together with clinical experience of memantine in Germany since 1982 confirm the safety of use and good tolerability profile of this medication at the recommended dosages (10 to 30 mg/day). Treatment with memantine reduces the global costs of the disease by lightening the burden on helpers and delaying institutionalisation of patients. These different studies have resulted in approval of memantine in this particular indication by the European Medicines Agency. The efficacy of memantine in mild to moderate Alzheimer's disease is currently being assessed. The preliminary results also appear to militate in favour of the efficacy of the drug in certain forms of vascular dementia. Finally, the good safety profile of combined use of this drug with antiacetylcholinesterases opens up a realistic perspective of bitherapy in Alzheimer's disease.

Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D-7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score15 or decreaseor = 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology.Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 +/- 3.5 to 14.8 +/- 6.4 in the 5 mg group vs a decrease from 31.6 +/- 4.7 to 18.6 +/- 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatments a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties in falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse events in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups.Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a dose at least as effective and slightly better tolerated than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

Rational and method - Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist -MASSA), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D -7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score15 or decrease 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. Results - Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 3.5 to 14.8 6.4 in the 5 mg group vs a decrease from 31.6 4.7 to 18.6 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatment a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties for falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse event in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. Conclusion - Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a at least as effective and slightly better tolerated dose than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

Medical information for the general public, patients and their families is a current Public Health priority. What information can be given to a patient suffering from schizophrenia, whose understanding and judgement capacities are supposedly affected by this mental disease? In the United States, 70% of psychiatrists inform patients of schizophrenia and diagnosis of schizophreniform disorder, while in Japan less than 30% do this. The lack of information given to the general public on the disease may contribute to reinforcing the difficulty in announcing the diagnosis. Indeed, the beliefs and attitudes of the patient, his/her family, the general population and health carers concerning the disease do not match up. However, the first two years seem to be a main issue for the subsequent evolution of the disease. No specific data on the attitude of French clinicians with respect to the announcement of the diagnosis is available. In the current legal context and in view of the advances in treatment, we have carried out a survey among French psychiatrists. It is an auto-questionnaire, transversal epidemiological, descriptive and analytical. The questionnaire was sent to a population of 12,958 psychiatrists. It comprised 48 questions: 7 referred to the socio-demographic and professional characteristics of the subjects, 22 to the attitude with respect to the announcement of the diagnosis to the patients, and the last 18 concerned the attitude with respect to the announcement of the diagnosis to the families. 1,691 questionnaires were returned by free post and analysed. The socio-demographic characteristics of the sample are close to those of French psychiatrists as a whole. The number of patients suffering from schizophrenia in the active files of the psychiatrists is 24% (+/- 21.4) on the entire sample. Approximately a third (37.8%) of psychiatrists deem it necessary to announce the schizophrenia diagnosis and approximately two thirds (69.5%) declare that they sometimes announce it. Among the patients suffering from schizophrenia in the active files of the psychiatrists who responded, approximately a third (34%) were informed of their diagnosis. The main reasons for not announcing the diagnosis are firstly the "reticence to give a diagnosis label" and secondly "the functional incapacity of the patient to understand the concept". The alternative diagnosis term most commonly used is "psychosis" (46.5%). However, 48.1% of practitioners state that the announcement of a specific diagnosis allows a better therapeutic combination. Depending on the proportion of patients suffering from schizophrenia in their active file presented in two categories (10% and10%), psychiatrists significantly most frequently announce the specific diagnosis (17.3% vs 25.3%, p10(-3). A statistically significant proportion of younger psychiatrists (44.4 vs 46.3, p10(-3) with fewer years of practice (14.1 vs 15.8), more often believe that it is necessary to announce the diagnosis. The rate of response (13.5%) for this type of survey seems high, which could indicate a high interest among psychiatrists with respect to this question. Our data showed the existence of a correlation between age, number of years in practice, type of practice and the proportion of patients suffering from schizophrenia in the active file on the one hand and the attitude of the psychiatrists with respect to the announcement of the diagnosis on the other hand. It is possible that the multi-disciplinary team work of public practice psychiatrists and the fact that they are more often confronted with schizophrenic disease facilitate the announcement of this diagnosis. In the survey population, the inability to give a diagnosis may be related to the questions of the practitioners about the capacity of the subjects to understand, the lack of precision of this diagnosis, the fear of disheartening the patients and the absence of curative treatment. The risk of suicide does not seem to be one

Clinical symptoms of bipolar disorders onset act as a prognostic risk-factor. Discrepancies of data are related with geographical or cultural conditions. Within a patient population of bipolar (ICD 10) in and out patients of a psychiatric department, manic or hypomanic disorders initiate the space disease in 33% of the cases theses features are similar within the western psychiatric population. In a maghrebian population this proportion reaches 50%. A percentage of 65% of bipolar 1 patients was found within our sample. Sex ratio is 1 for bipolar 1, when, for bipolar 2 disorders sex-ratio was superior to 1, in favor of females. Mean age of the first episode of the disease was younger for patients with a familial history of the disease.

In contrast to the well known chlorpromazine-induced cholestatic hepatitis, we report the case of a schizophrenic patient who presents a cytolytic hepatitis, without any prior hepatic disease. Mr G. was first hospitalized for depressive symptomatology. A pseudo-nevrotic schizophrenia was diagnosed. Pretherapeutic clinical and biological data were normal. A treatment with chlorpromazine 400 mg/day was given. At day 8, the patient was still anxious and began to be agitated. An increase to 500 mg/day of chlorpromazine posology and an addition of haloperidol 200 mg/day was implemented. At day 10, the following clinical symptoms appeared: 38.6 degrees C fever; headache; myalgia; epigastralgia and hypocondrium pain. Biological hepatitis disturbances (ALAT, 984 U/L; ASAT, 414 U/L) and hypereosinophilia with normal white cell count were found. Clinical and biological investigations were normal. Blood-culture, A, B, C hepatitis, HIV and CMV serologies were negative. Neuroleptic treatment was discontinued. Evolution to normality of the disturbances and biological data suggested a cytolytic hepatitis. Mr G... remained treated with flupentixol without side-effects. Phenothiazine-induced cholestatis is frequent, mild, and recovers spontaneously. The biological mechanism is supposed to be immunologic. Prevalence of biological hepatic disturbances is 10 to 20% with chlorpromazine in long-term treatment. More often, symptomatology is the same; jaundice, pruritus, abdominal pain, fever. Although pharmacological data suggest for a cytotoxic activity of phenothiazines, cytolytic hepatitis is poorly described. Maximum range of transaminase blood level reported in previous studies is about 400 U/l. This level is not clearly correlated with hepatic cell lysis. Few cases of hepatic necrosis have been reported. In all cases, preexistent hepatic injuries were observed. Chlorpromazine-induced cytolytic hepatitis is uncommon and cholestatic hepatitis mild. Biological hepatic parameters investigations remain necessary during neuroleptic treatment.

The concept of addiction is now of interest in psychiatry, but is a great subject of controversies. It is now recognized that as different disorders as alcoholism, drug addiction, bulimia, kleptomania, trichotillomania, pathological gambling are to be considered as addictive states. Other pathological behaviours could be included in the addictive spectrum (i.e. suicidal behaviours, compulsive spending). The comorbidity rates of these disorder are elevated in these populations. For example, high comorbidity rates are found between kleptomania and bulimia or drug addiction and pathological gambling. Polyaddictive states are well established. For some subjects, more than one addiction is present in life-time, but not occurring in the same period. We present three patients in whom different addictive states occurred alternately. All the patients had a history of compulsive spending and kleptomania, two of them had a history of bulimia and sexual compulsion. Some clinical characteristics were common: recurrent mood disorder, depression preceeding the addictive state, no psychoactive substance disorder. In all patients, severity of depressive state decreased when addiction appeared. Depressive symptoms varied inversely to addiction severity. The hypothesis about psychopathological links between kleptomania and bulimia on one hand and mood disorders on the other hand has been known for a long time. Kleptomania as other impulsive disorders is, for some authors, understood in the meaning of a "spectrum affective disorder". For these three patients, an antidepressant effect of the behavioural addictions is suggested. In fact, the addictions appeared alternately. The possibility of common psychopathological and/or biological mechanisms for behavioural addiction is supported by these clinical observations, that could contribute to the addiction concept validity.

Recent advances in knowledge about calcium's role as an intracellular regulator allow to broaden understanding of possible pathophysiologic mechanisms in affective disorders. An hypothesis emerge that bipolar illness arise from disorders in calcium-regulated functions. Given this hypothesis, some authors propose to describe the common profiles of action of the different mood-stabilizers: all the neural mechanisms that are hypothesized to explain various psychopharmacological treatments of bipolar illness involve functions that are critically controlled by calcium. Moreover, in every instance, a known action of lithium on calcium-dependent processes could account for lithium's prophylactic results. Similarities exist between the action of lithium and calcium antagonists like verapamil and nimodipine. From these considerations the hypothesis emerge that calcium antagonists could be an alternative pharmacological agent in the maintenance treatment of bipolar illness. Calcium antagonists have been found useful in this indication by a number of investigators. Given the safety and relative lack of side effects of calcium channel blocking agents, their potential efficacy in mood disorders, it is concluded that calcium antagonists may be an alternative choice in prophylactic treatment for bipolar illness, especially in patients who cannot be treated with lithium or carbamazepine. There is evidence for using verapamil at 240 to 320 mg a day, in 2 to 4 times. Some studies suggest that the association of lithium with calcium antagonist resulted more effective than lithium alone or calcium antagonist alone in the reduction of episodes of affective disorders. However, concomitant administration of a calcium channel antagonist and lithium present adverse interactions (lithium toxicity, cardiovascular accidents), probably because of synergistic toxic effects. Therefore, authors advise care in monitoring patients receiving the combination of these medications.

The adverse effects of electroconvulsive therapy (ECT) become rare due to the increased progress specially in avoiding cardiovascular side effects. In fact, several studies report ECT treatment performed with success and without side effects, in depressive patients presenting serious cardiovascular diseases (aortic anevrysm, cerebral venous angioma, cerebral infarct, aortic dissection...). Occurrence of cardiovascular complications can be prevented if an elevation of blood pressure or an arythmia occurring during the seizure are previously and correctly detected and managed. Hence an adequate anaesthetic premedication must be implemented. Usual protocols use atropine, hydralazine and hydro-chlorothiazide. However, ECT treatment should be avoided in patients requiring urgent surgical correction of their cardiovascular abnormalities. Also, patients and families must be informed on the benefit derived from ECT treatment and reassured on the therapeutic issue when ECT treatment is correctly managed. This case report concerns an 89 year old woman presenting a melancholic depressive state complicated with an aortic anevrysm, successfully treated with ECT.

The systematic and long term association of anti-parkinsonian drugs to neuroleptics is questioned by many authors because of their side effects and their toxicomanogenous risks whereas their efficiency in extrapyramidal effects of prophylaxis is not certain. This work aims at evaluating the interest of prescribing long term parkinsonian drug in association with neuroleptics. The study centered on 101 psychotic patients treated with neuroleptics, and followed on an ambulatory bases. 97% of this patients systematically received antiparkinsonian drugs. Extrapyramidal symptoms of varied intensity have noted for 61% of patients. The authors have compared, in double blind, the effects of the progressive and abrupt withdrawal of anti-parkinsonian drugs for 37 patients among the 101. These patients have been regularly treated for at least 6 months by neuroleptics (fluphenazine or pipothiazine) in association with trihexyphenidyle. They were randomly divided into 3 groups, and statified by sex and type of neuroleptic. For group I, composed of 13 patients, trihexyphenidyle is abruptly withdrawn and replaced by a placebo. For group II, composed of 11 patients, withdrawal is progressive for 2 weeks, trihexyphenidyle being replaced by a placebo. Group III, composed of 13 patients, is a sample group which went on receiving trihexyphenidyle. The results of this study showed that within the brutal withdrawal group (group I), 10 patients over 13 needed trihexyphenidyle again, whereas only 3 patients over 11 needed it in the progressive withdrawal group (group II). In the sample group (group III), one patient over 13 showed extrapyramidal symptoms, necessitating his leaving school. The global chi 2 is significant with p0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive functions are known to be impaired by ECT. The aim of this study is to differentiate the effects of electroconvulsive therapy on some cognitive functions according to the mode of application of the electrodes. The brief-pulse Thymatron DG apparatus allows to control four electrical parameters and to assess electroencephalographic data. The preliminary sample comprises nine patients suffering of major depressive disorder; they are randomly assigned to the mode of application of the electrodes, bilateral or unilateral to the non dominant hemisphere. Clinical evolution is surveyed by the Montgomery and Asbert Depression Rating Scale. Non mnesic functions are assessed: arousal by CFF (Critical Fusion Frequency), and attentional, motor and decisional abilities by CRT (Choice Reaction Test). Different mnesic function are studied by selective reminding test, cued recall test, block tapping test and picture fragmentation test. After treatment by ECT, verbal mnesic functions assessed by selective reminding test are impaired with the bilateral application. Whereas they are not modified with the unilateral application. The variance of CFF regains a physiological value in the bilateral group, but remains altered in the unilateral.

The authors present the development and the application of a structured interview guide for 4 depression scales: Hamilton Depression rating scale 17 items (HDRS-17), Montgomery-Asberg Depression rating scale (MADRS), Widlöcher Depressive Retardation Scale and also a fourth scale designed to evaluate the symptoms other than depression core symptoms (based on Depression and mania rating scale of P. Pichot). The final version of the guide was tested with 60 french depressed inpatients. This guide provides clinical information that permits the rating of the 4 scales in approximatively 45 minutes.

In this review the authors propose to study the impact of antidepressants on attention, memory and motor functions in healthy volunteers and depressed patients on single and long-term administration. After reviewing the principal cognitive functions, we examine the actual investigation means to conclude that the Critical Flicker Fusion Test (CFFT) is one of the most drug-sensitive tests. It permits a categorization in: sedative antidepressants that in single administration lower CFFT; compounds with no effect on CFFT and no deleterious cognitive effect; and finally substances that raise CFFT and may have psychostimulating properties. On single administration amitriptyline is the most sedative antidepressant on attention or motor level. It seems to produce negative effects on memory level. However, experimental trials give contradictory results. Imipramine in single administration also has sedative effects on memory and car driving capacity. However divergent results of experimental trials do not allow any conclusions of a clearcut negative cognitive effect. Memory impairments with imipramine appear at administration levels of 150 mg. Mianserin has a sedative impact on attention and motor level at low doses (10 mg). Among the tricyclics, nortriptyline has a highly dose dependent sedative effect that has been shown on attention tests (Time Reaction:TR, Digit Symbol Substitution Test: DSST). Among non-tricyclic compounds, doxepine lowers attention and motor performances. Maprotiline (75 mg) lowers CFFT and has a dose dependent effect. Trazodone also has a negative impact on attention tests. Finally viloxazine lowers CFFT but does not impair other attention or motor tests on a 100 mg doses. Buspirone, lofepramine, midalcipran and zimelidine are antidepressants with no effect on CFFT and do not have any positive or negative cognitive effect. On the other hand nomifensine, paroxetine and fluoxetine raise CFFT in healthy volunteers on single administration. Improvement of CFFT performances was found in an isolated manner for nomifensine and paroxetine on 30 mg doses with no other memory or motor effects. MAO-Inhibitors do not impair attention or motor function; thus moclobemide has no negative impact on memory, attention or car driving tests. Cognitive impact of antidepressants in depressive patients seems the same with those of healthy volunteers on single administration. In long-term administration antidepressants have different effects in healthy and depressed subjects. In healthy volunteers cognitive effects of most compounds are normalized after the second week of treatment. However, attention and motor performances with amitriptyline are normalized after 3 weeks of treatment. Sedative motor or cognitive effects of imipramine do not exceed 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)

The definition of treatment-resistant depression is variously interpreted. There is no agreement of different authors on its meaning. The present vagueness of criteria for the diagnosis of a refractory depression contrasts with the many studies reporting potentiation of antidepressants by lithium. De Montigny in 1981, after early works by Zall and by Lingjaerde, initiated this approach that still remains poorly understood in terms of biochemical mechanisms. A review of the controlled studies shows that the delay of antidepressant action varies and the term "lithium potentiation" does not seem totally relevant. From a pharmacological point of view, several types of data suggest a synergic potentiation rather than a true potentiation. This effect applies to all classes of antidepressants and improves about 50% of patients who did not respond positively to an adequate treatment received during 4 to 6 weeks. Many questions remain unanswered particularly concerning the lithium levels, factors predicting a positive response and the strategy for the maintenance treatment. Studies are necessary in order to compare the relevance of this potentiation technique with the mere substitution by another antidepressant and to understand the biochemical mechanisms underlying the synergic effect.

The choice of an antidepressant is not necessary during the initial phase of only treatment (acute treatment), it can be reviewed after one or two months (continuation treatment) and a prophylactic treatment may be discussed after a 6 months period (long-term maintenance treatment). Many reasons explain the need to readjust the dosage of antidepressant treatment or to change it: the nature and the gravity of the depression, the family and personal history of affective disorders, the level of side effects and above all the quality of the recovery. Thus the modification of a treatment can be considered according to 4 methods: modification of the psychotropes associated to antidepressant treatment, association of a second antidepressant medication, change of antidepressant medication, institution of a prophylactic treatment. A special aspect concerns the decision and the choice of the antidepressant treatment after recovery by E.C.T. Two types of treatment can be considered: most often a maintenance treatment of antidepressant medication is suggested. Prolongation of ECT may be justified for consolidation: 6 or 8 sessions after recovery, or for prevention of relapse: session every 3-4 weeks after recovery, and for a period of 2-3 years.

Medifoxamine (Clédial TM), a non tricyclic non MAOI antidepressant drug with a dopaminergic and serotoninergic mechanism of action, was compared to imipramine in a multicenter double blind trial. Patients suffering from DSM III-R major depression (without psychotic features), with a minimum inclusion score of 25 at the MADRS after an initial 7-day wash-out period, were randomly assigned to a 4-week treatment by either imipramine or medifoxamine, with flexible doses of at least 100 mg after 2 weeks of treatment. No associated treatment was permitted except for lorazepam 2 to 5 mg per day. Ninety eight patients were recruited by 20 centers throughout France. Eighty four terminated the 4-week protocol. Early terminations were due to serious adverse events (3), death on imipramine (1), protocol violation (1), refusal to continue (1), loss to follow up (1). The 2 groups of patients were comparable on inclusion. In the medifoxamine group (receiving a daily dose of 194 mg at day 28) the percentage of improvement in MADRS scores, the number of patients with a MADRS improvement of a least 50% and a final MADRS score inferior to 8, were not significantly different from the imipramine group (daily dose: 161 mg at day 28). No more difference appeared when several clinical variables were analyzed, in particular the DSM III-R melancholic, the Newcastle endogenous subtypes and the in or out patient status. The two treatment groups were also comparable on other scales (HDRS, HARS assessing anxiety, CGI).(ABSTRACT TRUNCATED AT 250 WORDS)

The anxiolytic efficacy of tetrabamate was evaluated in a multicentric double-blind study versus lorazepam and placebo, in 269 patients with a generalized anxiety disorder according to DSM III-R criteria. The anxiolytic activity of tetrabamate (at 900 mg/day) was significantly superior than that of placebo from day 7 of treatment and equivalent to lorazepam efficacy (at 4.5 mg/day). In the tetrabamate group, 55.3% were considered as "good responders" (as defined by a HARS score reduction equal or superior to 50%), versus 51.3 and 32.9% respectively in the lorazepam and the placebo groups (chi-square = 9.63, p = 0.008). Sheehan's scales (parts 1 and 2), Norris visual analogue scales, CHESS 84, CHESS complement 82 for withdrawal evaluation, physician's overall evaluation of efficacy and tolerance, were also used to assess the clinical effects of tetrabamate. The data on these measures confirmed the anxiolytic efficacy of tetrabamate and showed some advantages in the tetrabamate group in comparison with the lorazepam group: a better global tolerance at the study end point (day 35), a greater efficacy on some anxiety somatic items and lesser frequency and severity of withdrawal symptoms during treatment tapering off.

The place of electroconvulsive therapy (ECT) in the treatment of affective disorders is presently important and even inequaled in some depressive illness forms. But ECT is still controversial and its indications in the treatment of schizophrenia remain debated. In order to evaluate the place of this "vielle thérapeutique du futur" (39) in the treatment of schizophrenia, we reviewed the literature of the two last decades and tried to answer these questions. 1) Is ECT effectiveness in treatment of schizophrenic symptoms proved? 2) What is the effectiveness of ECT compared with other efficacious treatment? 3) Does the ECT + neuroleptic combination provide some advantage? and in which cases? The literature provides many studies in the topic. However, a considerable proportion of these studies make no use of modern methodological criteria. We only consider papers which: --give a clear diagnostic definition in patients groups and control groups, --use a standardized method of treatment, --use quantitative tools to evaluate results, --randomize treatment and use, when possible, double blind design. 1) Curative effects of ECT in schizophrenic symptoms: Brandon et al. (14) compare two groups of schizophrenic patients diagnosed according to PSE for schizophrenia and receiving equivalent doses of neuroleptics. The first group receives ECT when the other one receives simulate ECT. The former improved significantly better than the later. The difference persists but is no longer significant from the forth week of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The concept of disinhibitory agent is heterogeneous. If the disinhibitory property refers to inhibition in its clinical meaning, all psychotropic drugs can answer the denomination of disinhibitory agent when they are prescribed in some pathological entities. Traditionally this denomination refers to a few major tranquillizers, the antipsychotic action of which is linked to the improvement of the affective indifference and of the decrease of the psychomotor activity. However the pharmacokinetic data reveal that some potent sedative neuroleptics can become disinhibitors at high doses and some disinhibitory agents can become sedative substances at higher doses.

From the plasma and red cell kinetics of lithium in 43 patients having received lithium therapy for at least 15 days, the authors try to establish a correlation between intolerance and a variety of parameters examined. Statistical analysis reveals that: intra-erythrocytic concentration is a more reliable biological index than the lithium level; it can be modified by associated drug therapy; measuring the erythroplasmic ratio at different times of the day shows important variation within individuals. This type of kinetic study can identify biologically the 2 sub-groups distinguished by clinical examination: tolerant subjects (those on lithium therapy without any neurological signs) and poorly tolerant subjects.

The anxiolytic efficacy of tetrabamate was evaluated in 68 out-patients presenting an anxiety state with alcohol abuse according to DSM III criteria. The study followed a double-blind placebo-controlled design with parallel groups and lasted for 21 days. Anxiety was evaluated by the Hamilton anxiety scale, Norris visual analog scales, and the Hopkins Symptom Check List, along with the investigator's assessment. Safety was evaluated in terms of somatic symptoms (CHESS 84) and the physician's overall evaluation. The anxiolytic activity of tetrabamate (three 300 mg tablets/day) was significantly greater than that of placebo from seventh day on. There were no statistically significant differences in safety profile between tetrabamate and placebo. Moreover, in the tetrabamate group the significantly greater improvement in the scores of somatic symptoms indicates that the compound caused no notable adverse effects and its activity on somatic complaints (psychopathologic and/or toxic).

Two lithium intoxication cases due to an association with acetazolamide and niflumic acid are reported. They confirm the necessity of plasma lithium monitoring when a new drug is added.

The biochemical features of depressions able to guide the prescription of antidepressants are seen through a review of the literature. The papers were mainly focused on the peripheral catabolites of brain monoamines. Depressions characterized by low levels of 5 HIAA in the C.S.F. would predict a better efficacy of the antidepressants acting on the re-uptake of serotonin. The dosage of urinary MHPG seems to be a valuable index for the choice of the drug. Subjects with low levels response better to IMI, DE-IMI and NT, and those with normal levels to AMI. COMT activity and platelet MAO activity are may be a valuable index for the predictivity of the therapeutic results. Finally, the dexamethasone suppression test can be useful in order to guide the length of the treatment.

Psychiatric symptoms in AIDS have been noted in the literature. The case report of a young man with HIV showing psychotic features is presented. The course of the illness points to a possible schizophrenia incipiens. This raises two issues: the neurotropic potential of the virus and its involvement in the occurrence of these psychiatric troubles.