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SummaryAddiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.

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.

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.

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.

Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest. A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks. At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters. In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety. Copyright © 1999 Elsevier Science B. V. All rights reserved.

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.

Though the concept of impulsiveness is controversial, there are many attempts being made to measure this dimension. In this context, only psychometric measures are widely considered valid and are routinely in use. Barratt developed the first scale that specifically measured impulsiveness. Subsequently, various refinements have improved the validity of results. We have translated, without any significant problems, the tenth validated version of this scale (BIS 10) into French, and we have completed a factorial analysis. The scale was coupled with a self-administered questionnaire designed to assess anxiety. A sample of 280 subjects between the ages of 18 and 79 years (average age, 36.9) were recruited from the general population. Subject age was found to have a weak but nevertheless significant correlation with the impulsiveness rating. A principal component analysis (PCA) resulted in the first 9 factors explaining 55.6% of the variance. Another PCA of these factors allowed the identification of a second tier of 3 second order factors; these were closely related to Barratt's ranking. Our study confirms results from the scale's initial analysis--results which could not be subsequently reproduced. To our knowledge, this is the first French translation of an instrument that specifically measures impulsiveness and the first in which a factorial structure has been tested in the general population.

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.

Several arguments are in favour of the use of antidepressant drugs in alcohol-dependent patients, especially those acting on the serotoninergic system: (1) neurochemical data indicate the interaction between alcohol and 5-HT metabolism, (2) pharmacological studies show an improvement in the behaviour of alcoholized animals treated with antidepressants, (3) depression is a frequent disease in alcoholic patients. Tianeptine has been shown to be active in the treatment of depression in patients with history of alcohol abuse or dependence. In a first double-blind study performed versus amitryptiline, depression after withdrawal was improved by tianeptine, and biological abnormalities usually related to chronic alcohol intake tended to decrease. Similar results were found in an open study carried out on 277 alcoholic patients treated for 1 year. As these patients were depressed, no definite conclusion could be drawn from these results in respect of a specific action of tianeptine on alcohol dependence. Thus, a multicentre double-blind study has been performed which compared tianeptine (12.5 mg t.i.d) and placebo in 342 non-depressed patients fulfilling DSM-III-R criteria for Psychoactive Substance Dependence (alcohol). Other inclusion criteria were: daily alcohol intake higher than 80 g, minimum score of 3 on the Short-Mast Questionnaire, mean corpuscular volume above 98 fl and/or gamma Gt more than twice the upper limit of normal. The patients were treated for 9 months. The intention-to-treat population and the per protocol population were made up of 327 patients and 111 patients, respectively. The main efficacy criterion was the absence of alcoholic relapse (abstinence) defined by the patient's statements, the investigators clinical judgement and some biological parameters: alcohol blood levels, gamma Gt levels. Secondary criteria were the evolution of the alcohol consumption in the patients who relapsed, cumulative abstinence duration, a visual analogue scale for the evaluation of the appetence for alcohol and the clinical global impressions scale. The statistical analysis showed no difference between both groups in respect of the maintenance of abstinence (intention-to-treat and per protocol populations). In spite of the methodological problems of the studies in dependence (choice of the inclusion and efficacy criteria, especially), the preliminary results obtained with the serotoninergic antidepressants were not confirmed in the different trials performed in the maintenance of alcohol abstinence. The indication of tianeptine should be restricted to the treatment of depressive syndromes, which have a high lifetime prevalence in the alcoholic patient, and which have a noticeable role on the alcoholic relapse.

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 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.

Since the last decade of the nineteenth century, psychiatric nosology has been dominated by Kraepelin's binary system: the notion that the distinction between manic-depressive illness and schizophrenia identifies two separate diseases with differing symptom patterns and outcomes. However, Kraepelin recognised that intermediate states, as exemplified by Kasanin's concept of "schizoaffective" illness are common. In contrast to Kraepelin's separation of manic-depressive illness from schizophrenia, the concept of a continuum of psychosis implies that there are gradations of illness between unipolar depressive, through bipolar affective and schizoaffective illness, to schizophrenia. This concept is strongly supported by the majority of family studies. Moreover, no simple clinical demarcations of affective from schizophrenic illnesses can be made. The family findings are compatible with the hypothesis that the same gene or genes contribute to susceptibility to both schizophrenia and affective disorder: a single locus that may be variable between generations, and that is represented by homologous loci on the X and Y chromosomes.

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)

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

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

The potential activity of tianeptine in the prevention of depressive relapses or recurrences was evaluated in the course of a long-term multicenter study. Five hundred and ten patients were treated for a one-year period. During the first six months, 22 percent of patients responders to the treatment relapsed into depression or had a methodological equivalent of depressive relapse (a MADRS score equal to or higher than 25). This percentage of depressive relapses is comparable to those obtained with other antidepressants. After six months of treatment, 7 percent of patients with a stabilized recovery recurred into depression or had a methodological equivalent of depressive recurrence (a MADRS score equal to or higher than 25). An analysis compared this percentage with those obtained in the course of other studies. These percentages are classically more important. The role of diagnoses of depression was analysed. Percentages of depressive relapses and recurrences were also evaluated in the sub-sample of patients treated with tianeptine alone.

The effectiveness and good acceptability of tianeptine have been demonstrated in episodes of major depression without melancholia or signs of psychosis which are the valided indications of the tianeptine. In a way of research program, a multicenter study was conducted in 30 patients with D.S.M. III criteria for major depression with melancholia and signs of endogenicity as defined by the Newcastle scale. The patients were treated in a double-blind trial for 42 days. Administration of a placebo for 4 days prior to beginning the study was designed to eliminate rapid responders to placebo. The antidepressant effectiveness was evaluated on the Hamilton (HDRS), Montgomery and Asberg (MADRS) and global clinical impression (GCI) scales. The effect was satisfactory and statistically significant. Seventeen of the 30 patients (57 percent) included in this study improved with tianeptine (CGI-item 2). Results were comparable whatever the diagnosis established on DSM III criteria: bipolar depression, major depression, recurrent or isolated forms. The acceptability evaluated from patient complaints, measurement of blood pressure and laboratory tests was very satisfactory. Treatment was withdrawn in 14 patients with no subsequent withdrawal symptoms. These findings show that tianeptine can be prescribed with success for major depression episodes with melancholia (DSM III) and signs of endogenicity, although it cannot be concluded that patients should be given this treatment in first intention for this type of depression.

The authors have reviewed the records of 50 heroin addicts treated with methadone, a drug which, in France, is delivered under strict and daily supervision to only few patients. This retrospective study yielded the following data: (1) the success rate of maintenance treatment with methadone exceeded 50 percent and remained the same in HIV positive patients; (2) social and environmental factors predictive of poor response to methadone were the absence of professional activity at the beginning of treatment and a painfully disturbed family context. A history of trouble with the law was not a factor of poor prognosis. These data raise the problem of importance of an early treatment which might have a strong influence on subsequent developments.

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.

ECT is a reliable treatment of serious affective disorders more efficacious than antidepressants either used alone or combined with mood stabilizers or neuroleptics. Recurrent affective disorders refractory to all treatments presently available have been tentatively treated by prophylactic ECT since the beginning of ECT. In this study, 16 cases of recurrent affective disorders treated with maintenance ECT are discussed. Six continue to show a good response to maintenance ECT. Six remain improved although they discontinued ECT. ECT failed to improve 4 patients. Indications and inclusion criteria of maintenance ECT are defined. Good responses in cases refractory to all other treatment strategies are promising but still require prospective studies, difficult to implement, in order to confirm the efficacy of maintenance ECT.

One night sleep deprivation in 10 healthy volunteers was performed: none of them presented an abnormal dexamethasone suppression test (DST) during the following afternoon. In this experimentation, a short deprivation of sleep does not alter DST. Etiopathogenic hypothesis of DST abnormalities (and other factors) have been discussed.

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.

Platelet MAO activity was measured in 75 hospitalized depressed patients and in 31 healthy subjects. Plasmas post dexamethasone cortisol levels were examined in 73 patients. Results indicate that higher platelet MAO activity does not occur in all, but only in male major depressed patients. No relationship between changes of MAO activity and specific clinical subtypes was found. Platelet MAO activity is not different between DST suppressors and DST non suppressors. The authors suggest that platelet MAO activity may be related to non specific factors such as sex, age, but not to diagnosis of depression.

The association between changes in platelet MAO activity and Major Depressive Episode have been demonstrated. Cyclical changes in sex hormones serum levels had never been related with changes of MAO activity in depressed patients. Platelet MAO activity, oestrogen serum levels, progesterone serum levels and testosterone serum levels, have been measured in drug free depressed patients: 22 men and 42 women. This study demonstrates no relationship between serum levels hormons and platelet MAO activity, measured in men and in women. If young women are separated from menopaused women, platelet MAO activity is negatively correlated with oestrogen serum levels, in non menopaused women. Significance of this variation in studies about the use of MAO as a biochemical marker in depression is discussed.

A case of status epilepticus with transient motor deficit is reported in a 66 year old male treated with fluvoxamine. Fluvoxamine is supposed to induce few epileptic seizures. The patient had no previous history of epilepsy. Two factors seem to have favoured the occurrence of epilepsy: presence of an incipient arteriopathic impairment, cortical and subcortical brain atrophy and perhaps drug overdosage causing a tremor in the days before the epileptic fit.

The authors report a trial on the antidepressive activity of L.5-H.T.P. The clinical population is relatively homogeneous; it consists of melancholic patients, aged over 50. The results are inferior to those obtained with other antidepressant therapies. They do not verify that L.5-H.T.P. has an antidepressive action in elderlies. However, the authors do not put aside that L.5-H.T.P. can be interesting in some varieties of depression.

The authors try to determine the incidence of long-term lithium treatments on sleep, appetite and sexual behaviour. The study was conducted in fifty outpatients of both sexes who have been for at least six months on lithium only and whose mood disturbances are stabilized. In two thirds of the cases of this clinical study, lithium seems to have beneficient qualitative and quantitative effects on sleep as opposed to other psychotropic drugs which cause discomforting sleepiness. Lithium seems to influence appetite slightly although it is responsible for the gain in weight in a fourth of the treated outpatients. Half of the subjects consider that lithium modifies their sexuality towards a decrease of the desire without modifying their capacities of realization. In a comparison study conducted with the psychotropic drugs that had been administered before, the repercussions of lithium on sexuality appear thus opposite to those of psychotropic drugs, major tranquilizers and antidepressants which impair the capacities without reducing the desire. Despite the specific side effects on some instinctive functions, lithium seems to be a treatment well lived by the subjects.

The antidepressant effect of citalopram, a specific inhibitor of the reuptake of serotonin, was explored in an open phase II study involving twenty-one patients hospitalized for depression. Fourteen patients responded, six did not and one was excluded from the study. These preliminary results suggest that citalopram is an effective, well tolerated antidepressant.

The dosage of the whole tryptophan and of the free tryptophan was conducted in 16 normal subjects to establish reference values and in 12 schizophrenic subjects among whom 7 were under treatment and 5 were not. The method of dosage is made by spectrofluorimetry by increasing the native fluorescence of tryptophan. The results give mean values for the free tryptophan and for the ratio of the free tryptophan to the whole tryptophan values that are higher in the schizophrenics than in the normal subjects used as reference, while the whole tryptophan seems to be little modified ; this increase is more noticeable in the schizophrenics under treatment. The limited number of the cases studied does not enable us yet to establish correlations between the increase of the free tryptophan found in some cases and the nature of the schizophrenia, its age and its evolutivity or even the clinical response to the treatment. However, some figures for the free tryptophan being very much higher than the mean value in some schizophrenics, suggest ways of research for understanding the pathogenisis of schizophrenia and the mechanisms of the therapeutic action of the psychotropic drugs.

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.

Intellectual, affective and motor inhibition is part of the syndrome encountered in: drug withdrawal in addicts especially with opiates; hebephrenia. Amineptine a new antidepressant agent with psychoanaleptic properties has been studied in these patients. Considering this psychotonic activity was logical to test both the tolerance of this compound in drug addicts and the risk of delirious reactivation in schizophrenic patients. The open study in 19 patients shows an effect of amineptine: -on inhibition and loss of activity, apragmatism and deterioration of social behaviour; -a subjective improvement of intellectual performance. And moreover: without reactivation of preexisting delirious ideas in schizophrenic patients; without drug addiction in treated toxicomaniacs.

The plasmatic levels of free, sulfoconjugated and total dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of noradrenaline, have been measured in thirty DSM3 major depressive inpatients and in thirty healthy controls matched for sex and age. DOPEG levels have been measured by a radioenzymatic assay. Almost fifty per cent of depressed inpatients were D.S.T. non suppressors, thirteen patients were unipolar and thirteen bipolar. Plasmatic DOPEG levels were significantly lower in depressed patients as compared to healthy controls despite a wide interindividual range of DOPEG values. However, the ratio of free over conjugated DOPEG was not statistically different in the two groups. DOPEG levels were slightly higher in the female population of healthy volunteers but not in the depressed patients. In the healthy volunteers, but not in depressed patients, there was a trend for free DOPEG to increase and for conjugated DOPEG to decrease with age. There was no statistical correlation between the DOPEG levels and Hamilton Depression Scores. Also plasmatic DOPEG values were not different in uni or bipolar patients and in DST suppressor or DST non suppressor inpatients. The significance of the decrease of plasmatic DOPEG levels in depressed patients is discussed: this diminution may reflect a deficiency in noradrenaline metabolism in CNS or else may be attributed to other factors e.g. alteration in circadian rhythms, differences in motor activity, in level of anxiety, in sleep and feeding behaviors; cotreatment with benzodiazepine and opiate compounds; monoamine oxidase activity.

Commercialized in the U.S.A. a few years ago, the loxapine succinate appears to be interesting among neuroleptic compounds. Used in 28 chronic schizophrenics, 19 of which were neuroleptic resistent patients, the parenteral route proved to be anti-psychotic and sedative in 26 patients. The usual daily dosages were between 100 and 200 mg. The local and general tolerances were good. The side effects were mild and essentially vegetative. The therapeutic efficiency seems to be better at the same dosages with the oral form than with the parenteral form.

The study concerns the use of a new antidepressant, tianeptine, as a treatment of depressive and/or amotival syndrome, in 30 drug addicts, detoxified from opiates. From a thymoanaleptic point of view, 85% of the patients exhibit a positive result after 28 days of treatment with 37.5 mg/day. These good results are confirmed by the evolution of the Hamilton Depression Rating Scale global score, which significantly decreases from D0 to D14 and from D14 to D28. The acceptability of the antidepressant is good. Anticholinergic side-effects are very uncommon. Tianeptine appears devoid of any obvious psychostimulant or sedative effect. The drug compliance, estimated by counting the tablets, is very satisfying: there is no tendency to a spontaneous increase of dosing. The follow-up of the patients after drug cessation has not shown any symptoms suggesting psychological or physical dependence towards the drug. During this study in subjects particularly predisposed to the abuse of psychoactive drugs, tianeptine has not induced anything suggesting the possibility of drug abuse or tolerance.