[Present data and treatment schedule of aripiprazole in the treatment of schizophrenia]. / Données actuelles et modalités d'utilisation de l'aripiprazole dans le traitement de la schizophrénie.

Among the second generation antipsychotics, aripiprazole presents a new pharmacological profile, basically differentiated by a partial agonist effect on the D2 and D3 dopaminergic receptors. Five short-term efficacy studies, conducted on 1648 patients presenting with schizophrenia or acute relapse of schizoaffective disorders, demonstrated the greater efficacy of aripiprazole than the placebo and comparable efficacy to that of haloperidol and risperidone. The short-term tolerance profile was characterised by a lesser incidence of the extrapyramidal side effects and drowsiness than with haloperidol. Two thousand six hundred and eighty five patients were followed-up over a period of 26 to 52 weeks in five clinical trials versus a placebo and haloperidol, olanzapine, quetiapine and risperiodone: demonstrated efficacy in maintaining the response to treatment and on the delay before relapse was comparable to the other antipsychotics. The classical side effects of antipsychotics decreased in the long-term. Versus olanzapine, a glucid and lipid profile, clearly in favour of aripiprazole, was completed by a lesser incidence of hyperprolactinaemia. Aripiprazole is effective on all the dimensions of schizophrenia: the positive and negative and depressive and anxious symptomatology. It appears to be of interest, notably on the cognitive dimension, which should motivate more in-depth exploration of its place in the treatment in the early stages of schizophrenia. Its therapeutic schedule and the methods of initiation are an essential criterion to the success of treatment, notably during the substitution of other antipsychotics. The clinical and pharmacological originality of aripiprazole would justify the terminology of a "third generation antipsychotic".

[Schizophrenia diagnostic announcement in a French psychiatric unit]. / Annonce du diagnostic de schizophrénie au sein d'un service de psychiatrie de secteur.

Announcement of schizophrenia diagnostic to the patients is a topical issue in France. The evolution in clinical practices, a better efficiency in therapeutic procedures and the fundamental right of the patient to obtain information have initialised the discussion of its interest. Spontaneous claim for information from the patient is rarely observed although awareness troubles might be reported at the instauration of the mental disorder or during its evolution. Methodological studies concerning the diagnostic announcement are limited. Except the Bayle studies recently published, only a few publications are available in France about the knowledge of their pathology and their need to be clearly informed. French scientific literature deals generally about medico-legal aspects of this information and consisted of survey about diagnostic announcement. International literature is more abundant and presents positive and negative aspects of the announcement. An information procedure of schizophrenia announcement to the patient has been developed in our hospitalisation unit of psychiatry. This procedure has taken place on the basis of the literature data, our specificity and our clinical experiences. For some Anglo-American psychiatrists who have proceeded to semi-structured interview in order to announce the diagnostic, information to the patients might improve the clinical relationship. Thus, compliance to the treatment is significantly increased. The ability of the patient to recognise the symptoms of the disease and to accept their consequences and the treatments is associated to a better social prognosis, daily activities and response to the treatment. The announcement impact justifies the prescription of neuroleptics, treatment that is notoriously perceived as prejudicial by the patients themselves or more commonly in the basic population. To obtain compliance to the treatment, a satisfactory acceptance of the mental disorder is required. Compliance is based on satisfactory information in order to gain the cooperation of the patient and its relative (10). Atkinson has classified four main types of arguments, the ethical principle to be informed, talk to explain and give sense to the symptoms, reduce the feeling of guilt perceived by the patient and his relative and enhance the collaboration between the patient and the nursing staff. According to Ferreri and Bayle studies French psychiatrists reluctance to announce schizophrenia diagnostic are the following: lack of request or of interrogations asked by the patient about their disease, diagnostic and prognosis uncertainty and irreversibility of the disease, complexity of the pathology and its origin which hinder an accessible explanation, cognitive disorders frequently observed with schizophrenic patients which may be associated with difficulties of understanding information, destabilization of the patient-nursing staff relationship and social stigmatisation risks. Other arguments like reluctance to give a "label" to the disease, too abstract diagnostic, a negative social vision and the possibility of discouragement for the relative are classically retrieved in French literature. In fact, divulgation of the term schizophrenia involves a panel of negative representations and is hindered by the confusion in the social imagination of such a term related with lost of control, quintessence of madness, dangerous behaviour possibilities, evil and incurability. Some psychiatrists do not transmit information arguing that significant obstruction of the future may be consecutive to the information. They prefer to use vague terms more socially acceptable like "nervous breakdown or depression, atypical or emotional disorder, dissociative troubles...". Information to the patient about his mental disorder is more frequent in psychiatry for affective, anxious and additive troubles than for schizophrenia. Our procedure of diagnostic announcement has been elaborated after preliminary discussion with the medical and nursing staff. Diagnostic of schizophrenia announcement has been presented by weighing the pros and cons according to the intemational literature. It clearly appeared that benefits for the patients prevail on the drawbacks. Nevertheless, inclusion and clinical supervision have to be carefully precised in particular to verify the ability to receive information. Short term objectives: deliver progressively information to the patient about his disease by means of an active and educational process with hope and optimism using a accessible language (explanation of each terms used with the intention of being well understood); quantify the impact of diagnostic announcement on the schizophrenic patient using clinical rating scales during a period of one month (clinical interview at day 1, day 7 and day 28). Mid term objectives: improve the global supervision and autonomy of schizophrenic by means of a therapeutic project helping the patient to become an active partner in the monitoring of his mental disorder; enhance a psycho-educational program after the procedure of announcement in order to optimise the observance of his treatment, increase his quality of life and answer to the requests of his relative; 45 patients (age 29.3 +/- 8.8 years old) have been included to be informed on their diagnostic since the elaboration of this procedure during a time period of 24 months. Time interval between the beginning of their pathology and the delivering of this information was 4.7 years. Most of them (56%) presented a paranoid type of schizophrenia. In most of the cases, the patients did not know their diagnostic or declared suffering from a diagnostic, which was erroneous; 80% of the 45 patients have complied with the procedure until its end. On more than 24 of following after the instauration of the diagnostic announcement procedure, these patients ha ve presented satisfactory observance to the medical supervision (medical consultation and drug intake); 60% of the patients were regularly present to their medical appointment. The number of patients included (45 patients) appears small compared to the time interval of the study (24 months) but was significant according to the great changes in our clinical approach. Thus, this procedure was not systematically applied, in particular the patients who did not want to be informed on their disease. Is it clinically relevant or not to announce diagnostic of schizophrenia to the patient? This issue remains questioned according to the few studies published at the present time, any consensus has been clearly presented on formal indications or contra-indications. If on an ethical side, this information appears logical, the medical and nursing staff should require special care. Special care must be taken before delivering information to the patients; each situation must be evaluated in order not to comply with an ideology of total and inadequate information, which could have serious consequences. Nevertheless, it appeared clearly that information must be given to stabilized patients with satisfactory insight. Moreover, psychotherapeutic projects become easier because patients awareness and understanding towards pathological symptoms are greatly improved. Partnership between patient and medical staff is the key of this dynamic and psycho-educative procedure, which opens new horizons in our therapeutic prospect.

[Management of suicidal adolescents: a clinical audit in 76 hospitals]. / L'audit clinique appliqué à la prise en charge hospitalière des jeunes suicidants: bilan d'une expérience auprès de 76 établissements.

We describe the implementation and results of a clinical audit of the management of suicidal adolescents in hospital that was carried out as part of the French national suicide prevention programme. The ANAES definition of a clinical audit is: "an assessment method using defined criteria that compares care practices with accepted standards and measures the quality of these practices and the results of care with a view to improving them". Standards for the audit were derived from the clinical practice guidelines published by ANAES (French National Agency for Accreditation and Evaluation in Health) in November 1998. They comprised 15 criteria covering ressources available and procedures implemented: patient management in hospital (9 criteria), contacts made with the patient's environment outside hospital (2 criteria) and preparation for discharge from hospital (4 criteria). Participation in the audit was voluntary. Overall, 76 hospitals from the 10 regions of France with a suicide prevention programme took part in the audit and made 1,554 observations. The number of observations per hospital ranged from 1 to 42. Compliance with the criteria was > 80 % for 5 criteria, 50-80 % for 3 criteria, and < 50 % for 7 criteria. A total of 26 hospitals, proposed a structured improvement plan, ie, scheduled, ordered and ranked measures with a definition of responsibilities and follow-up. Of these 26 hospitals, 15 had implemented the three ANAES recommendations (setting up a working group for the project, using a grid to analyse results, drafting a structured report) whereas only 5 of the 50 hospitals that did not come up with an improvement plan had done so. An operational outcome thus seems related to compliance with the audit method. Three years after the audit was set up, 17 hospitals took part in a second round. Improvements were noted for 12 criteria, mainly for those giving poor results in the first round. However, these improvements concerned few hospitals (eg just 4 hospitals for the criterion with the worst result in the first round). A worsening of compliance was noted for 3 criteria. In conclusion, hospitals were found to comply with guidelines relating to the management of suicidal adolescents in hospital. However, compliance with guidelines relating to making contact with the patient's environment outside hospital and preparing for discharge was less good. Although the hospitals taking part in the audit endorsed our method, our experience showed that, to be effective, clinical audits need methodological support and a well-defined time schedule.

Promoting quality improvement in French healthcare organisations: design and impact of a compendium of models and tools.

Relevant and user friendly information should be provided to professionals who wish to promote quality improvement in healthcare organisations (HCOs). In response to requests from French HCOs, we designed a compendium of methods and tools for use in quality improvement. Its contents were based on a critical review of the literature, face-to-face interviews with three industrial/business experts in quality, the views of 13 healthcare professionals knowledgeable in quality issues, and comments from over 40 potential users of the compendium. Overall, 14 methods and 20 tools relevant and applicable to the healthcare sector were identified. They were classified according to their main thrust, explained in detail, illustrated with specific cases from the literature or from personal experience, and published as a loose leaf compendium. The compendium was posted on the worldwide web and presented to healthcare managers in September 2000. It has become one of the most popular ANAES publications (approximately 5400 downloads over the first 6 months), partly because all French HCOs are legally bound to undergo accreditation which has been set up and is being implemented by ANAES.

[Hepatic tolerance of atypical antipsychotic drugs]. / Tolérance hépatique des antipsychotiques atypiques.

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.

[Transcranial magnetic stimulation in depression]. / La stimulation magnétique transcrânienne dans la dépression.

Among the new therapeutic techniques in psychiatry, transcranial magnetic stimulation (TMS) seems to bring a profit in the treatment of depressions. It uses the principle of inductance to generate a magnetic current, which in turn activates cortical neurons. Stimulation is highly focused and interests specific regions of the cerebral cortex. This therapeutic technique is generally well tolerated. Side effects are rare, the most hampering one is epileptic seizures. It is favored by high frequencies (above 5 Hz) and arises mainly with patients having a history of personal or family epileptic seizures. The first open trials, quickly confirmed by controlled studies showed the efficiency of TMS in depression. With depression, double blind randomized trials, using high frequencies, stimulation of the left dorsolateral prefrontal cortex give positive results with significant decrease of scores on depressive scales applied to resistant and non resistant depressions. Some studies have stimulated the right dorsolateral prefrontal cortex using low frequencies. The decrease of scores is also significant on depressive scales. The modulating effect of rTMS on cortical excitability of the brain justifies this distinction between high and low frequencies, high frequencies having a facilitating effect whereas low frequencies have an inhibitory effect.

Assessing the impact of a consensus conference on long-term therapy for schizophrenia.

OBJECTIVE: Our aim was to assess the impact of six recommendations regarding drug prescription on the clinical practices of French psychiatrists. The recommendations were part of the conclusions of a consensus conference entitled "Long-term therapy of schizophrenia" (Paris, January 1994). METHODS: The impact of the conference was assessed on the basis of awareness of the existence of the conference, knowledge of its conclusions, and actual changes in clinical practice. We performed: a) a survey of a representative sample of 396 psychiatrists 2 years after the conference; and b) an analysis of changes in drug prescriptions in a cohort of 2,407 patients with schizophrenia under treatment at the time of the conference. RESULTS: Overall, 78% of interviewed psychiatrists were aware of the existence of the conference and 70% of its conclusions. Declared prescription practices conformed with conference conclusions about 60% (10%-95%) of the time. No difference in practices was noted between psychiatrists who were aware of the recommendations and those who were not. Single neuroleptic prescriptions increased in the cohort study in line with the main conference recommendation. The increase was small, but significant from 51.1% to 56.4%, and mainly concerned patients recently put on treatment. Contrary to recommendations, prescriptions of anticholinergics plus neuroleptics inexplicably rose from 48.2% to 54.3%. CONCLUSION: Small changes in prescription habits occurred in the wake of the consensus conference, but we cannot really ascribe them to a direct impact of the conference. Despite the great pains we took in disseminating the conclusions of the conference as widely as possible, it is clear that a more forceful action plan (e.g., including continuous medical education) is required.

[Quality assurance in drug treatment by prescription drug analysis in a psychiatric treatment facility]. / Démarche qualité dans le circuit médicament grâce à l'analyse pharmaceutique des ordonnances dans un établissement de soins psychiatriques.

This article reports pharmaceutical analysis of the medical prescription in a psychiatric hospital. This study estimates the impact of the pharmaceutical interventions on the security of the treatment prescribed. This pharmaceutical system is based on individual prescription and on pharmaceutical analysis of this document. This analysis consists in checking high dosage prescription, detecting drug interaction, omission or frank prescribing errors and providing pharmaceutical advice to the physicians. In 1997, hospital pharmacists have intervened in 510 prescriptions:--315 high prescribing dosages were checked. In 7.3 percent of these cases, an error of dosage was detected;--66 drug interactions were communicated. Thirteen interventions corresponded to a forbidden association according to the Vidal therapeutic register;--53 pharmaceutical advices were performed; 12 interventions were related to a physiological or a pathological characteristic of the patient which forbid the use of the treatment;--more over, 34 omissions or frank errors were detected through the medium of our interventions; 25 errors could be considered as clinically relevant. In conclusion, the interventions rate was estimated to 3.6% of the new prescriptions. In 14.1% of these cases, they appeared as clinically significant. These rates are lower than those described in the traditional global distribution for which pharmaceutical analysis is not performed. This report has underlined the interest of pharmaceutical care by analysing the medical prescriptions.

[The study of the impact of the consensus conference "Strategies for long-term therapy of patients with schizophrenia"]. / Etude de l'impact de la conférence de consensus "Stratégies thérapeutiques à long terme dans les psychoses schizophréniques".

UNLABELLED: The case management, treatment and psychosocial rehabilitation of schizophrenic patients is an important part of the activity of the psychiatric sector and takes up many human, scientific, organizational and financial resources. The best way to reach satisfactory results for the individual patient is still uncertain and current practice in France shows noticeable variations that have been rarely investigated in terms of outcome. A consensus conference (CC) on "Strategies for long-term therapy of patients with schizophrenia" was therefore held in Paris in 1994 to produce accurate guidelines designed to help both clinicians and patients and to improve practice. It was organized by the French Federation of Psychiatry, the National Union of Friends and Relatives of Mental Patients, and the National Agency for the Development of Health Evaluation. The conclusions of the CC were mailed, in the form of a booklet, to members of these associations (psychiatrists and relatives) and were reported in the medical and general press. METHODS: The impact of the CC was judged by (a) the psychiatrists'awareness of the existence of the CC, (b) their knowledge of its conclusions, and (c) changes in practice. The following were analyzed: press coverage; requests for the booklet; the results of a survey of a representative sample of 396 psychiatrists two years after the CC; prescription changes in the public sector in a cohort of 2,407 schizophrenic patients under treatment at the time of the CC; prescriptions to psychotic patients by a representative sample of psychiatrists in private practice. RESULTS: Awareness: Articles on the CC were published in 27 journals and newspapers, 30,000 booklets were distributed and 8,348 were mailed in response to 1,121 spontaneous requests; 78% of the psychiatrists interviewed said they were aware of the existence of the CC and 70% said they were aware of the conclusions. Knowledge: The psychiatrists' declared practice conformed with CC conclusions 41%-85% of the time depending on the recommendation. No difference in practice was noted between the psychiatrists who said they knew of the recommendations and those who said they did not. Changes in practice: A significant but small improvement in prescription habits was noted for a principal recommendation ("just one neuroleptic is enough"). One-neuroleptic prescriptions increased from 51.1% the year before the CC to 56.4% two years after the CC. The increase mainly concerned the most recently treated patients. However, during the same time-span, prescriptions of anti-cholinergics plus neuroleptics rose from 48.2% to 54.3%. CONCLUSION: It is difficult to attribute changes in practice to a CC. However, the impact of the CC seemed real even if inconstant and not great enough. Clearly, to enhance impact an action plan is needed. It should include corrective measures and focus on additional dissemination efforts, teaching and training programs, and updating of guidelines if necessary.