[Management, needs and expectations of patients suffering from bipolar I disorders (The ECHO study - France)]. / Prises en charge, besoins et attentes de patients souffrant de troubles bipolaires I (Étude ECHO - France).

AIM: The ECHO study is the first French study directly asking patients with bipolar I disorders on the history and experiences of their disease, their perceptions of care, their sociofamilial relationships, and their expectations regarding what should be done by healthcare professionals and their environment. METHOD: Three hundred euthymic patients suffering from bipolar disorder I were interviewed using a semi-standardized evaluation through telephone interviews. These patients were selected according to the quota method of nationally representative INSEE 99 to be representative of the French population. RESULTS: Ninety-nine percent of patients consulted at least once for psychological signs before the correct diagnosis was established. The average age at the time of diagnosis was of 30.1 years (± 11.3). The average time between first consultation for psychological symptoms and diagnosis is about 5 years. In 92% of cases, the psychiatrist is the health professional that made the diagnosis; 74% of patients were also followed by a general practitioner. One hundred percent of participants had been hospitalized for manic episodes (criterion for inclusion in the study) and 86% were also hospitalized for depressive symptoms. The experience of hospitalization is positive (feeling of security for 84% of the sample, feelings of being helped for 81% of the sample), although these experiences are also associated with the perception of confinement (52% of the sample). At the time of the interview, 97% of these patients were followed by one or more health professionals. Only 34% of these patients were taking a mood stabilizer (lithium, anticonvulsant or atypical antipsychotic with indications in France for bipolar disorder), while 44% were taking an antidepressant and 38% were taking anxiolytics; 84% of patients had experienced side effects related to their current treatment. Acceptance of the disease is difficult and only 56% of patients personally feel they suffer from bipolar disorders. Patients believe that their mental health problems have a significant impact on their lives, including impact on their self-esteem and happiness. Relationships with family, friends but also sexual relations are affected. Even in the euthymic phase, 44% of patients have difficulties in their daily tasks. Three quarters of patients said they had already experienced rejection or discrimination related to their disease. Finally, patients gave a score of 6.4 out of 10 to assess the impact of the disorder on their quality of life. Patients request more dialogue with health professionals and a more personalized treatment, taking into account side effects. They also want more information on the treatment. They would also like to be supported, together with their families, and advised on how to cope with the disease.

[Therapeutics approach of adult patients with acute and chronic psychotic states: REALITE survey]. / Approche thérapeutique d'une population de patients présentant des troubles psychotiques aigus ou chroniques: enquête REALITE (Recherche Epidémiologique sur l'activité de la Loxapine et ses Indications en Thérapeutique quotidiennE).

A retrospective observational pharmaco-epidemiological survey was conducted during 24 weeks between October 2004 and March 2005 in metropolitan France (384 investigators) to more clearly define the use of loxapine in acute and chronic psychotic states. The objective of this national survey was to specify the clinical and therapeutic profile of patients managed by this antipsychotic in two cohorts of adult patients: one in "acute phase" (prescription of loxapine during the previous 4 weeks), the other in "maintenance phase" (prescription of loxapine for more than 8 weeks). The two groups of the recruited population (1,511 patients) presented identical sociodemographic data. Selection criteria were adapted to the data collected to ensure statistically relevant analysis: 696 patients in acute phase and 633 patients in maintenance phase. The acute phase group was predominantly composed of known patients (82% of patients had a psychotic history) with schizophrenia (47%) or mood disorders (57%) who had already presented acute episodes (an average of 5.4). The current episode consisted of a state of agitation (88%) lasting an average of two weeks, requiring hospitalization (87%), scheduled admission [HDT (admission at the request of another person) in 47.5% of cases and HO (statutory admission) in 40.8% of cases] and prescription of loxapine monotherapy (56%) at a mean daily dose of 177,3 mg. The maintenance phase group comprised a population of known patients (87.5%), schizophrenics (63%), presenting psychotic symptoms (dissociation 82%, delusions 74%) or mood disorders (71%) requiring voluntary hospitalization (78%) for a mean duration of 180 days and a prescription of loxapine monotherapy in 28% of cases at a mean daily dose of 131.6 mg. The loxapine-haloperidol combination (21%) was prescribed more frequently in the second group in the case of chronic disorders; in the other cases, loxapine was coprescribed with the main second generation antipsychotics: risperidone (16%), olanzapine (16%), amisulpride (11%). CGI assessment of the overall study population revealed a marked or very marked clinical improvement with no significant adverse effects in more than 80% of cases.

The role of captodiamine in the withdrawal from long-term benzodiazepine treatment.

BACKGROUND AND OBJECTIVES: Discontinuation of benzodiazepines can be associated with the emergence of a withdrawal syndrome which compromises successful termination of treatment. The objective of the present study was to evaluate whether a six week administration of captodiamine during benzodiazepine discontinuation could prevent emergence of a benzodiazepine withdrawal syndrome and thus facilitate discontinuation of these drugs. SUBJECTS AND METHODS: A controlled, randomised, double-blind trial of captodiamine versus placebo was conducted in 81 subjects presenting mild to moderate anxiety and treated for at least 6 months with a stable dose of benzodiazepine. Each subject was gradually weaned from benzodiazepines over a 14 day period using a tapering dose schedule and received captodiamine (150 mg/d) or placebo for 45 days from the beginning of the weaning period. OUTCOME MEASURES: The primary outcome criterion was the extent of withdrawal symptoms assessed using the Tyrer Benzodiazepine Withdrawal Symptom Questionnaire. Secondary outcome criteria were; self-evaluation of tension, anxiety, drowsiness and slowing of physical and mental performance using visual analogue scales; quality of sleep using the Spiegel questionnaire; anxiety using the Hamilton Anxiety Rating Scale; and cognitive function using a driving stimulation test. RESULTS: Analysis of the primary study criterion revealed a statistically significant difference (p < 0.0001) in the emergence of withdrawal symptoms between the two groups in favour of captodiamine at two, six and eight weeks following initiation of therapy. These results were supported by significant beneficial effects of captodiamine on the majority of secondary outcome measures. The switch to captodiamine was associated with an improvement in vigilance, which may be an advantage for the overall safety of the anxiolytic treatment, for example with regard to road safety. Discontinuation of captodiamine was not associated with the emergence of rebound anxiety. CONCLUSION: Captodiamine represents an interesting strategy for achieving benzodiazepine substitution with a low risk of dependence or impairment of cognitive function. Further clinical studies addressing the anxiolytic activity and safety of captodiamine in such subjects are merited.

Switching antipsychotic medications: general recommendations and switching to amisulpride.

As more and more novel antipsychotic agents are introduced, the need for practical guidelines on switching these medications is becoming increasingly important. Indications for a switch include situations where the patient or his family/caregiver requests a change in medication, where the patient cannot tolerate current treatment, where they have comorbid physical or psychiatric conditions or where they have achieved only a partial remission, are refractory to treatment or have relapsed. Cross-tapering is generally the most acceptable method of switching, although abrupt withdrawal may be necessary in some cases, such as when a patient develops a severe or acute reaction to their current treatment. Possible problems of switching include the risk of discontinuation reactions and the re-emergence of psychotic symptoms. The pharmacological profile of amisulpride means it has a relatively low potential for interactions with other drugs and may be started while discontinuing the previous antipsychotic. It should be started at the target dose for the patient's current symptoms. A retrospective questionnaire among 60 patients switching to amisulpride treatment was undertaken to identify the characteristics of patients switching antipsychotics and their reasons. Patients were switched from a variety of antipsychotic medications, both traditional (42% of patients) and atypical (58%). Most patients (87%) had at least two reasons for changing medication, with lack of efficacy, adverse events and treatment optimisation before reintegration being the most common. Contrary to recommendations, 89% of patients were switched abruptly between medications. A total of 62% of patients received amisulpride doses in the range 400-800 mg/day and most (72%) required no dose adjustment. The great majority of patients (87%) switched to amisulpride without problems.

[The use of therapeutic isolation and confinement in psychiatry. A prospective study]. / Utilisation de l'isolement thérapeutique et des contentions en psychiatrie. Enquête prospective.

Despite recent developments in psychopharmacology and a better understanding of agitation patterns in psychiatric patients, the use of seclusion and restraint procedures remains a matter of daily practice. Little or no time is spent on its teaching in a formal way. There is almost no literature on these issues, and it has grown only since legal procedures initiated by patients, which forced practitioners to spend some time analysing these methods. Facing this problem, we realized a prospective study at the CHS de la Savoie, in Chambéry, so as to clarify the current modes of these procedures. This study was led among 460 secluded patients, during one year. 11 data were studied, such as the duration of the seclusion, the reason and the medical history, the desire of the patient to be liberated ... The review or awareness of certain variables may give clinicians a better perspective on the use of procedures which, unfortunately, continue to be the cause of deaths in psychiatric practice.

[Self-assessment questionnaire of alcoholic craving (ECCA Questionnaire: Behavior and Cognition in Relation to Alcohol: French translation and validation of the Obsessive-Compulsive Drinking Scale]. / Auto-questionnaire d'appétence alcoolique (questionnaire ECCA: échelle de comportement et de cognitions vis-à-vis de l'alcool: traduction française et validation de l'OCDS (obsessive compulsive drinking scale).

Clinical, neurobiological and neuropsychological hypotheses suggest that the dimension of alcohol craving includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. Anton et al. (1995) developed a 14 items self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS) which includes items for assessing three dimensions: global, and the obsessive and the compulsive subdimensions. In this study, we included 156 patients, 105 men and 51 women, who met DSM IV diagnostic criteria for alcohol dependence. The mean age of our population was 39.1 +/- 11.2 years without difference between sexes. We did not found any correlation between the CAGE score and the OCDS total score or the obsessive and compulsive subscores (respectively, r = .15, r = .10 et r = .18). Moreover, we did not found any correlation between OCDS scores and mean daily alcohol consumption (r = .18, r = .16, r = .19). This could indicate that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the "state of illness" for alcohol-dependent patients. The test-retest correlation for the OCDS total score was .95 and the obsessive and compulsive subscales test-retest correlations were .93 and .89 respectively. The internal consistency of the items of the OCDS was high (alpha = .89). Principal component analysis had identified in the french version of the OCDS, three factors accounting for 63.5% of the total variance. These results indicate that the french version of the OCDS seems to validly measure a dimension of alcohol dependence. The ease of administration, reliability, and concurrent validity of the OCDS makes it particularly useful as an outcome measurement tool for various clinical therapeutic protocols in alcoholism.

[What is the meaning of "stabilization" in schizophrenic patients?]. / Que recouvre le terme "stabilisation" des patients schizophrènes?

UNLABELLED: The notion of stabilization in schizophrenia has been investigated, in France, through a survey of 875 psychiatrists. This survey, which has been conducted on the 9th, 10th and 11th of December 1997, looked into the clinical, therapeutic and socio-demographic variables, and the means of patient management, which are used by psychiatrists to ascertain that their patients are stabilized. The data was collected by each psychiatrist by way of a questionnaire administered to his or her next three patients, either at the hospital or in private practice (2,464 questionnaires were completed). RESULTS: 65% of the patients seen during this survey were considered stabilized by their psychiatrist (n = 1,597). The most common clinical presentation was of the paranoïd type. An insiduous onset of disease seems to be correlated with an absence of stabilization. Stabilization appears to be estimated at a given time rather than over a time period, since over half the patients who were considered stabilized had suffered at least one relapse over the last 2 years, and had been rehospitalized an average of 2.4 times over that period. In terms of drug therapy, they received 1.4 neuroleptic drugs, which does not differ markedly from the 1.5 neuroleptics administered to patients who were considered non stabilized. Co-prescriptions of anticholinergic medications, benzodiazepines and antidepressants were very common in these patients considered stabilized (49.9%, 39.8% and 24.8% respectively), which is similar to that observed in their non-stabilized counterparts (47.6%, 45%, 8% and 26.4%, respectively). Patient follow-up remained above an average of 1 patient visit per month (an average of 8.9 visit over the last 6 months), despite the fact that patients were considered stabilized. Two primary criteria were used by psychiatrists to determine that a patient was stabilized: treatment compliance and the absence of positive symptoms. However, 43% of the patients which were considered stabilized still presented with positive symptoms. Negative symptoms were also very prevalent in these patients (65%), as well as concomitant depressive signs (36%) and anxiety (64%). CONCLUSION: Even though the concept of stabilization remains difficult to define, it appears that schizophrenic patients are considered by their psychiatrist as stabilized on the grounds of good treatment compliance and decreased positive symptoms. Therefore, even in these so-called stabilized patients, enhancements are still possible, as symptoms remain present.

[Attempted suicide and alcohol dependence: results of an epidemiologic survey]. / Tentative de suicide et dépendance alcoolique: résultats d'une enquête épidémiologique.

OBJECTIVES: The relationship between alcoholism and suicidal behaviour has long been recognized. The present study examined the lifetime prevalence of suicide attempts in alcoholic patients and the impact of comorbidity, namely with depressive anxiety disorders and antisocial personnalit disorder in alcoholic patients who attempted suicide. METHODS: In a cross-sectional design including outpatients referring for alcohol dependance according to DSM III-R criteria, we used a specific standardized and structured interview allowing DSM III-R diagnoses. RESULTS: We include 507 patients (343 males of 164 females). The mean age at the intake of the study was 43.2 (SD:9.6) years without difference between males and females. 129 patients (25.4%) had attempted suicide during their lifetime. The proportion of female was found higher than males among suicide attempters (41.9 vs 29.3%; p < or = 0.001). Age of onset of alcoholism was found younger in suicide attempters than non (p < or = 0.01), either in males and females. Moreover, we found that alcoholic suicide attempters more often reported family histories of alcoholism than did nonattempters. As regard lifetime comorbidity, major depression and drugs misuse were found more frequent in alcoholics who attempted suicide (p < or = 0.001). Moreover, we found a higher prevalence for Panic Disorder and Social Phobia in male suicide attempters.

[Evaluation of efficacy and tolerance of amisulpride in treatment of schizophrenic psychoses]. / Evaluation de l'efficacité et de la tolérance de l'amisulpride dans le traitement des psychoses schizophréniques.

Amisulpride is a benzamide derivative atypical antipsychotic characterized by selective blockade of dopamine D3 and D2 receptors, limbic selectivity and preferential blockade of dopamine autoreceptors at low doses. Its efficacy on predominant negative symptoms of schizophrenia at low doses, and on the positive symptoms at doses from 400 to 1,200 mg/day has been demonstrated in several controlled studies. The aim of our study was to assess the use in psychiatric clinical practice under naturalistic conditions, efficacy and safety of amisulpride and patient's ability to cope with social skills during a 3-month period of treatment with a follow-up at 6 months. A total of 445 patients (293 men and 152 women), between 18 and 45 years of age, were included in the study DSM III-R criteria of schizophrenia, paranoid type (295.3), or schizophreniform disorder (295.4) were required for inclusion. The patients received amisulpride with flexible dosage between 600 and 1,200 mg/d during a 3-month period (792 mg/d +/- 318). Evaluation was based on the Brief Psychiatric Rating Scale (BPRS), on the Positive And Negative Symptoms Scale (PANSS), and on Clinical Global Improvement scale, completed at D0, D14, D28, D60 and D90. Safety was also assessed with a comprehensive statement of adverse events and with the Simpson-Angus scale of extra pyramidal symptoms. A scale of social adaptation (Echelle d'Adaptation PsychoSociale) was completed at D0, D90 and D180. During the 3-month period of treatment, 124 patients (27.9%) dropped out the trial, including 24 cases of inefficacy and 27 cases of concomitant events. Intent-to-treat analysis showed a significant improvement of BPRS scores (40.2 vs 67.6; p < 0.0001), of positive PANSS scores (13.9 vs 27.7; p < 0.0001), and negative PANSS scores (17.45 vs 28.3; p < 0.0001) between D0 and D90. CGI results confirmed these figures. Follow-up assessment at D180 showed a sustained response on BPRS ans PANSS scores. Amisulpride was well tolerated in the study, with 21% of patients reporting adverse events, in majority psychiatric or endocrine disturbances. Only seven adverse events were assessed as serious. Extra pyramidal symptoms remained low during the study, as measured with Simpson-Angus scale. The EAPS scale showed a significant improvement of social adaptation during the treatment, with a sustained response during the 3-month follow-up period. In conclusion, 600-1 200 mg/d of amisulpride is an effective and well tolerated treatment of schizophrenic disorders, as demonstrated through this 3-month study carried in a large sample of 445 patients. Besides results suggest that under treatment with amisulpride in schizophrenic patients patients' ability to social adaptation can be improved, which could facilitate their rehabilitation.

[Absence of frontal lobe dysfunction and working memory deficits in young schizophrenic patients]. / Absence de dysfonctionnement frontal et de trouble de la mémoire de travail chez de jeunes schizophrènes.

The impairment in tasks requiring intact frontal lobe functions has been repeatedly shown in schizophrenics. However, the relative roles of confounding factors, like duration of the disease, social withdrawal, or antidopaminergic medication, are not clearly demonstrated. We studied the performance of 12 young active patients, with chronic residual schizophrenia that had recent onset, and 12 control subjects, with frontal lobe tests and with a battery designed to explore working memory. The results show normal performance in schizophrenia. The small number of patients does not allow definitive conclusions, but this study suggests that a frontal dysfunction may not be present early in the evolution of schizophrenia in active patients.

[Social trajectory and schizophrenia]. / Trajectoire sociale et schizophrénie.

On the occasion of the Clozapine symposium we have had cause to reflect on the social life-histories of schizophrenic patients. After an analysis of a cohort of 40 patients aged over 65 years, whose medical records had been kept up since the start of their disease, we have set up a methodology which enables us to study the social life-histories of these patients. Our aim is ultimately to compare the course of the disease with the treatments received by these patients and the therapeutic structures they have been offered. For this purpose, we shall study three criteria of social exposure: 1) Autonomy, 2) Integration into the family, 3) Integration through work. The aim of the present paper is to record our initial analytical findings in these three years.

[Alzheimer's disease and informed consent of incapacitated people: propositions aimed at improving the procedure]. / Maladie d'Alzheimer et consentement du majeur protégé par la loi: proposition pour améliorer la procédure.

Ethical considerations must be given priority when deciding whether or not to include an Alzheimer's Disease patient in a study leading to direct individual benefits. Although the law applies to ethics, the Huriet-Serusclat law was nevertheless written in the spirit of the major ethical declarations of the last 50 years (Nurenberg, Helsinki, Tokyo...) in order to protect patients from abusive decisions, whether these decisions were for or against the patient receiving treatment. This paper describes an incident during a phase II trial involving patients with Alzheimer's Disease. Four incapacitated patients protected by guardianship had given their informed consent to take part in the study. Their participation required that the informed consent be signed by the guardian as well. By misunderstanding of the law, the guardian transmitted the decision to the guardianship judge. Surprisingly, the guardianship judge refused permission for all patients to take part in this therapeutic trial against the wishes of the patients. Even more surprisingly, it appeared clearly that this judge was not thoroughly informed of each detail of the law. Prevention of this kind of situation might require modifications of the responsibilities of the CCPPRB. It is suggested that before the start of a study the CCPPRB should give a precise definition of the way in which incapacitated persons should be treated.

[Frontal lobe dysfunction and depressive state: relation to endogenous character of depression]. / Dysfonctionnement frontal et état dépressif: relation avec le caractère endogène de la dépression.

A dysfunction of dorsolateral prefrontal cortex (DLPF) in major depression is suggested by functional imagery and comparative neuropsychology. However, assessment of frontal lobe syndrome with DLPF-dependent tests led to controversial results. To clarify these findings, we administered 5 of these tests (Wisconsin Card Sorting Test, Stroop Test, Trail Making Test, Tower of Toronto, verbal fluency) to 16 major depressive subjects and their 16 controls, before and after 21 days of treatment. Furthermore, we tried to assess the prognostic value of frontal lobe dysfunction, and its relation with the endogenous or exogenous nature of the depression on the one hand, the severity of the depression on the other hand. Our results suggest that the presence of a frontal lobe syndrome (defined by impaired performances at 3 tests or more) is only noted in endogenous depression; after treatment, no impairment is detected. No correlation is found with the severity of the depression. Frontal lobe syndrome does not seem to indicate poorer prognosis for current depressive episode.

[Prazepam drops versus 10 mg prazepam tablets in anxious patients in ambulatory care]. / Etude prazépam goutte versus prazépam comprimé 10 mg chez des patients anxieux traités en ambulatoire.

A multicentric study has been conducted with a new prazepam formulation (drop) which has been compared with 10 mg tablets. The aim of the study was to check the clinical equivalence of the two formulations. Nine generalists and 9 psychiatrists participated in this double blind study. One hundred fifty four patients with DSM III generalized anxiety criteria were included in this study and received prazepam at an average dosage of 20 mg per day. There were 11 drop outs: 6 in the tablet group and 5 in the drop group. The statistical analysis was done on 143 patients. Before treatment the two groups were equivalent. There was a very significant decrease (p less than 10(-4) in Hamilton anxiety scale scores, physician visual analogic scale and patient visual analogic scale with no difference between both groups. The vigilance, measured by the Mini-Folstein scale, was significantly increased (p less than 10(-4) in both groups. The tolerance was also similar: 14 patients in the tablet group and 10 in the drop one complained of asthenia and somnolence.

[Several critical aspects of the value of peripheral markers in depression (TRH test and dexamethasone depression)]. / Quelques aspects critiques sur la valeur des marqueurs périphériques dans la dépression (TRH test et freination à la dexaméthasone).

Studies of depression carried out for over 10 years have led to the discovery of biological tracers for depression. The authors have performed numerous TRH and dexamethasone tests and in their opinion, the present enthusiasm for these tests should be tempered. In several aspects the various values attributed to them seem to be questionable. Owing to the difficulty in codifying these tests, the authors question their diagnostic, pronostic, therapeutic and predictive values. The authors' own experience as well as the evolution of the publications throughout the world have been taken into consideration. Finally, the problem of interferences and the doubtful specificity of endocrine tests for depression have been dealt with.

[A new injectable delayed-action neuroleptic with sedative and antipsychotic action: cis-(Z)-clopenthixol decanoate. Clinical trials]. / Un nouveau neuroleptique retard injectable à action sédative et anti-psychotique: le décanoate de cis (Z) clopenthixol. Essais cliniques.

70 psychiatric patients were treated with a depot preparation of cis (Z) clopenthixol decanoate, a new sedative and anti-psychotic neuroleptic. The mean dosage interval was two weeks, an amount of drug from 50 to 1000 mg for each I.M. injection. Significant improvements were obtained on thinking disturbance, hostile-suspiciousness and anxious-depression symptoms groups. Thus, paranoid schizophrenia seems the best indication of cis (Z) clopenthixol decanoate. Side effects (parkinsonism, weight increase) were of low intensity, and no depression was observed. This new long-acting depot neuroleptic may be used not only in hospitalized chronic schizophrenic patients, but also in outpatients as maintenance treatment: excellent results were obtained in such patients with a very low (less than 200 mg) fortnightly dosage. Advantages and indications of cis (Z) clopenthixol decanoate are discussed.

[Neurological complications of tricyclic antidepressive agents]. / Complications neurologiques des antidépresseurs tricycliques.

The tricyclics are antidepressive drugs in widest use today. They are one of the most effective of the psychotropic agents and would be used more often if it was not for the complications. In this article we consider the neurological stimulation that results in undesirable cardio-vascular responses that are the main side-effects of these drugs. First, a brief statement is made about the action of the antidepressive drugs on the synapses for both their therapeutic effects and their side-effects are produced at this level. Despite the many patterns of complications that can occur, it is important to remember that these drugs are still very useful in managing depression and they should be the treatment of choice in depressive syndromes.

[Therapeutic trial of gamma-vinyl GABA, an inhibitor of GABA transaminase, in tardive dyskinesias induced by neuroleptics]. / Essai thérapeutique du gamma-vinyl GABA, un inhibiteur de la GABA-transaminase, dans les dyskinésies tardives induites par les neuroleptiques.

Oral gamma-vinyl GABA, an irreversible inhibitor of GABA-transaminase, was given to 10 patients with neuroleptic-induced tardive dyskinesia (7 chronic simple schizophrenics and 3 chronic paranoid schizophrenics). Dyskinesia was reduced in 8 of 10 cases. Aggravation of dyskinesia and major psychomotor sedation was observed in two elderly patients with senile dementia. In addition, with regard to schizophrenic symptoms, gamma-vinyl GABA appeared to have beneficial effects on affective withdrawal and retardation, while hallucinations seemed to be aggravated.