[Comparative analysis of the financing of follow-up and rehabilitation care institutions and public mental health institutions: Application for innovative and expensive drugs]. / Analyse comparative du financement des établissements de soins de suite et réadaptation et des établissements publics de santé mentale : application pour les médicaments innovants et onéreux.

Pharmacotherapeutic care is now expanding in public mental health institutions. Annual grants are funding the public psychiatric field, hindering access to therapeutic innovation and expensive medications due to long length of stay. On the threshold of the French Healthcare & Social Services Ministry "Ma Santé 2022" plan ("My Health 2022"), there is a risk of altering the continuum of care because of the complexity of the financing of certain high added value therapies. Despite a desire to adapt the system to meet constantly changing health needs, no actions have been taken to this date in psychiatry, with no funds being allocated for valuable medication, in contrary to follow-up care and rehabilitation structures, to our knowledge. This reinforces the discrepancy with the evolution of research, and further widens the gap in inequalities between health sectors. Optimising the funding of expensive medicines in psychiatry would make it possible to reduce the stranglehold of current allocations. Following the example of recent reforms in the follow-up care and rehabilitation structures, extra funds for high value-added therapies would make it possible to reduce complex medical decisions: from prevention to reintegration, patient care continuity would be vastly guaranteed.

[Evaluation of prescription practices of long acting injectable risperidone in French hospitals]. / Enquête des prescriptions de rispéridone injectable à libération prolongée dans neuf centres hospitaliers du réseau PIC.

INTRODUCTION: Atypical antipsychotics or antipsychotics of second generation are still recommended by guidelines for primary use in the treatment of psychotic disorders because of their better neurologic safety and efficacy. However, they require daily dosing, thus compromising their overall efficacy whereas conventional depot neuroleptics provide constant pharmacologic treatment but induce extrapyramidal adverse effects and poor efficacy on negative symptoms. Long acting injectable risperidone (LAIR) is the first long-acting second-generation antipsychotic. Registered in October 2003 and launched in March 2005 in France thanks to Kane et al.'s and Fleischhacker et al.'s reference studies, it was supposed to provide the advantages of conventional long acting formulations of antipsychotics over those of an atypical agent. OBJECTIVES AND METHODS: The aims of this study, with the description of the prescription practices of LAIR in naturalistic conditions, were to assess the place of this new drug in psychotic medication, with the efficiency value measured by treatment discontinuation rate and analysis of the reasons for discontinuation, and to assess whether the prescriptions practices are or not in adequacy with guidelines and reglementation. In June 2005, we conducted a one-year naturalistic non-randomised open-label study in nine French psychiatric hospitals, members of the PIC network: were included all the patients who received LAIR every 2 weeks, between July 1st 2005 and November 30th 2005. RESULTS: Prescriptions of 216 patients were examined for 1 year. LAIR was used off label for 15% of the patients. Ninety-two percent of patients were hospitalized at the beginning of the treatment while 72% of the treated patients had dropped out one year after the first injection. Regarding the nature of previous antipsychotic treatments prescribed in the last three months before the first injection of LAIR: 31% patients had received a first generation antipsychotic, half of which had received a depot antipsychotic of first generation and 69% had received a second-generation antipsychotic, among which half had received oral risperidone. The principal reason noted by the clinicians for starting the new formulation was non-observance with anterior treatments. However, oral antipsychotic treatment preceding the first injection was used less than 4 weeks for one third of the patients. When this treatment was oral risperidone, average posology at the first injection was 6.7 ± 2.4 mg per day; it was 7.4 ± 2.1 mg per day for the patients who received the higher dose of LAIR (50 mg/2 weeks). So, it seems that some patients were not sufficiently stabilized by their antipsychotic before the beginning of the long acting treatment. The result was a significant rate of treatment discontinuations (53%) in the following year, principally caused by the withdrawal of the patient's consent and an insufficient response to treatment. CONCLUSION: This investigation provided the opportunity to analyze the prescriptions of a new formulation drug in routine clinical practice. It confirms the need for respecting the authorized indications and the recommendations of good use of a drug to avoid the failures of treatment and also the importance of the role of the pharmacist in recalling it to the physicians.

[Study on clozapine treatment at the Charles Perrens Hospital in Bordeaux, 15 years after its marketing]. / Enquête observationnelle de prescription de la clozapine au centre hospitalier Charles-Perrens à Bordeaux, plus de 15 ans après l'AMM en France.

INTRODUCTION: The international consensus conferences concerning schizophrenia and the authorization to market (French AMM) reserve this molecule for the treatment of resistant schizophrenia. Resistant schizophrenia, as defined by the marketing authorisation, corresponds to the absence of improvement in a patient's state despite two successive treatments with antipsychotics, or at least an atypical drug at an adequate dose for a sufficient length of time. OBJECTIVES: Our investigation compares hospital practices to the marketing authorisation and guidelines regarding resistant schizophrenia. METHODS: All clozapine prescriptions delivered by the pharmacists at the Charles Perrens Hospital were recorded during the month of February 2007. General information concerning the patient and his or her treatment were collected, based on different support teams set up in the hospital. First, the hospital administrative program was used to manage the patients. Then, the treatment establishment form, filled out by psychiatrists before the beginning of the treatment, listed all previous treatments given to the patient and indicated any inefficacy or intolerances to prior treatments. Then, a program monitored the delivery of this molecule and finally, prescriptions were recorded to describe present treatment. RESULTS: Our study consisted of 61 patients, mostly male subjects averaging 40 years of age, single, who had been under psychiatric care for about 15 years, and were, for the most part, professionally inactive. Clozapine was prescribed for schizophrenic (90%) and for bipolar patients (10%). Clozapine was also often prescribed for patients whose illness had not improved with prior treatments. The average dose was of 489 mg/day for patients considered stable, i.e., those for whom clozapine was prescribed with efficacy observed for a sufficiently long time. It was associated in 88% of all cases with another psychotropic: anxiolytic (68% of cases), normothymic (26% of cases), antidepressant (16%) and antipsychotic (42%). DISCUSSION: In practice, clozapine seems to be efficient in bipolar disorders, although the marketing authorisation does not envisage this indication. It is never prescribed first, as some recommendations indicate, even though the follow-up of certain treatments does not always seem adequate to appreciate their non-effectiveness. Seldom prescribed alone, clozapine is often associated with another antipsychotic, a practice not favoured by many experts. Our investigation thus confirms the increase in co-prescriptions, particularly in hospital, for patients who have not improved with clozapine alone, a case that is barely taken into consideration in consensus conferences. With the lack of innovative molecules, psychiatrists are prompted to associate several antipsychotics, with the risk of supporting iatrogenic medication, whereas the experts reserve the relevance of such associations because of a lack of randomised studies.

[Prescribing patterns of antipsychotics in 13 French psychiatric hospitals]. / Enquête de pratiques de prescription des antipsychotiques dans 13 centres hospitaliers du réseau PIC.

INTRODUCTION: The commercial introduction of atypical antipsychotics, called second-generation antipsychotics (SGAs), a few years ago, has led to a world-wide reappraisal of the established treatment strategies for people with psychotic or bipolar disorders. They permitted improvements in the pharmacologic management of psychiatric diseases. As compared to conventional neuroleptics or first-generation antipsychotics (FGAs), they promised better efficacy especially on negative symptoms and cognitive impairments of psychiatric diseases and, at the same time, better tolerance on neurological side effects. Now, they have shown other side effects and they have a higher acquisition cost than FGAs. OBJECTIVES AND METHODS: The aim of this paper is to describe and analyse the prescribing practices of antipsychotic drugs in French psychiatric hospitals for adult inpatients and to compare them with other surveys and guidelines. In June 2004, we conducted a one-day, cross-sectional, observational and naturalistic study in 13 hospitals, members of the PIC network. RESULTS: Two thousand one hundred and ninety-two prescriptions with antipsychotic treatment were collected. One thousand one hundred and fifty-four prescriptions (52.6%) included a SGA, but the FGAs were the most prescribed (65.8%; n=2259), principally cyamemazine (24.7%). There was one antipsychotic in 50.7% of prescriptions, two antipsychotics in 42.2%, but the second neuroleptic used was a sedative (82.6%), principally cyamemazine. Multiple antipsychotics were present in 1081 prescriptions (49.3%), with an average number of 1.57 antipsychotics. A mood stabiliser, an antidepressant, an anxiolytic and a hypnotic were coprescribed in respectively 37, 30.5, 65.1 and 41.6%. There were 2.48 psychotropic drugs associated with the principal antipsychotic; in total, with correctors of side-effects of the antipsychotics, there were 3.38 drugs per prescription. The SGAs aimed more often for psychotic (F20-F29) patients (61.9% versus 43.3% with FGAs), who were males (61.4% versus 68%), younger (42.6 years versus 44.1 years; p<0.02), with higher average daily doses, more associated with other neuroleptics (p<0.0004) and less associated with anticholinergic antiparkinsonian agents (p<10(-4)) than FGAs. Compared to other surveys, these results showed that the SGAs have become the first-line treatment for psychiatric disorders. The highest average daily doses corresponded to treatments of psychotic patients and, hence, the values might largely exceed the authorized maximum doses. Furthermore, in more than half of the cases, an FGA, generally a sedative, was associated with an SGA that did not comply with the principle of monotherapy established by the national and international guidelines; that also annulled the expected benefit of the SGAs on the awakening, cognition and the neurological tolerability of the treatment. The coprescriptions of the other psychotropic drugs to neuroleptics also remained the rule in psychiatry, showing all the complexity of pharmacological psychiatric medications. Prescriptions also included treatments for side effects of antipsychotics; even on the prescriptions including the SGAs, there was the coprescription of anticholinergic antiparkinsonian drugs, the deleterious character of which one knows on cognition. This resulted in a difficulty of understanding the prescription for the patient, associated with reduced compliance and increased risks of pharmacological side effects. The heterogeneity of the situations of crisis in psychiatric hospitals could make the strict application of guidelines' recommendations difficult. Nevertheless, the educational interventions in psychopharmacology for patients and the training campaigns for psychiatrists and nurses are necessary to improve the therapeutic management of the patient and ensure him/her optimal quality of life. CONCLUSION: This kind of survey, far too rare, was very important because it showed the routine clinical settings in which these new drugs were really used. The results showed that SGAs appeared to take the place of the FGAs used in the treatment of psychoses, particularly schizophrenia, but also in the treatment of mood disorders and they reflected actual clinical practices. Other surveys must be conducted to see whether our study confirms the general trend concerning the use of these drugs and, therefore, to reassess these prescribing practices.

[Long-acting injectable risperidone: naturalistic study in three hospitals in Aquitaine]. / La rispéridone injectable à libération prolongée: enquête d'utilisation dans trois établissements d'Aquitaine.

INTRODUCTION: Injectable risperidone is the first long-acting second-generation antipsychotic. A middle-term naturalistic study has been conducted with the first treated patients of three psychiatric hospitals in Aquitaine. METHOD: Two evaluations of these patients were performed by psychiatrists: the first before the beginning of treatment and the second after six months. Data on efficacy and tolerance of the drug were obtained from in-patients who were unstable or non-compliant with their previous treatment. Two scales were used to highlight efficacy (positive and negative syndrome scale (PANSS) and clinical global impression (CGI)). All adverse events had to be notified in a general form and AIMS was used for extrapyramidal symptoms. Patient's quality of life was auto-evaluated by TEAQV. The pain on injection was assessed by the patients on a visual analogic scale. RESULT: Patients were treated between February 4th and December 4th 2004. Among the 71 treated patients, 27 (38%) discontinued treatment before the six months, due to: lost to follow-up (11.3%), consent withdrawn (9.9%), insufficient response (7%), adverse event (2.8%) or unknown reason (7%). The results of efficacy and tolerance concern 37 patients (52%) with a mean age of 32.8 (+/-7.8) years. Patient's PANSS score was 86.6 (+/-21.4) at the beginning of treatment. Mean decrease of this score was 13.2 after six months. Efficacy of the product is shown by 40.5% of the patients who decreased more than 20% of their initial PANSS score. CGI showed a global improvement "mild" to "great" with 46% of "strongly" to "very strongly" improved patients. Adverse reactions reported are known with risperidone: extrapyramidal symptoms (29.7%), weight gain (13.5%), dry-mouth syndrome (13.5%), hypotension (8.1%), sexual disorders (5.4%) and hyperprolactinemia (2.7%). Extrapyramidal symptoms were still the most common adverse events, as in the initial evaluation. Patients claimed their quality of life was unchanged after six months in comparison with the initial evaluation. They evaluated pain at injection site as moderate (2.6/10). DISCUSSION: The results of efficacy have been compared to the results published in the two studies that made it possible to obtain marketing autorisation of the drug in USA. The PANSS results for efficacy were not statically different from the results of the two reference studies (except for negative symptoms: there was no statistical difference observed between initial and final scores in our study, probably due to the small size of the sample). This study highlights several positive aspects for long-acting injectable risperidone (innovating pharmaceutical presentation: aqueous suspension which contains microspheres, moderate pain at injection site, efficacy in 40.5% of initially unstable patients, discharge and no rehospitalisation in most patients, decrease of the use of anticholinergic products) but also shows several negative aspects (frequency of injections--every two weeks--, high percentage of treatment discontinuation, same adverse event profile as oral risperidone, no improvement in quality of life). CONCLUSION: Despite the small size of the sample, this study presents a view of the use of the drug in realistic conditions and appears to show that long-acting injectable risperidone is probably the most appropriate treatment for stable, discharged patients.

[Urticaria paradoxically aggraved by H1 antihistamines]. / Urticaires paradoxalement aggravées par les antihistaminiques H1.

BACKGROUND: H1 antihistamines (anti-H1) are the treatment of choice in chronic urticaria. We report five cases of urticaria, induced or aggravated by H1 antihistamines. METHODS: The immunoallergological investigations included prick-tests and intradermal tests with the antihistamine responsible for acute urticaria. RESULTS: The skin tests confirmed the non-IgE dependent nature of the urticarial eruptions and anti-leukotrienes (montelukast, Singulair) were effective in controlling chronic urticaria in 3/4 patients. DISCUSSION: Two hypotheses are discussed to explain the paradoxical aggravating effect of H1 antihistamines on the urticaria: 1) the patients are sensitive to the toxic, pro-inflammatory effect of the drug, which is the source of nonspecific activation of mast cells; 2) the fact that the urticaria is sensitive to anti-leukotrienes suggests that histamine is not the principal mediator of urticaria in these patients.

[Immediate hypersensitivity is rarely implicated in drug induced urticaria]. / L'hypersensibilité immédiate est rarement en cause dans les urticaires médicamenteuses.

INTRODUCTION: The unexpected appearance of acute urticaria during the course of drug treatment gives rise to the following question: is it an allergic urticaria (due to an immediate hypersensitivity: IgE mediated specific immunity) or is it pseudo-allergic? We report our findings in an immuno-allergological study of patients who were sent for drug intolerance which presented as immediate hypersensivity (urticaria, angiooedema, anaphylactic shock). METHODS: A prospective study was conducted including all the patients who were sent to the unit for urticaria or angiooedema type drug intolerance. Patients were questioned about previous chronic urticaria and also about urticaria after taking different medicines. The clinical examination looked for a dermographism. All the patients then took skin tests for immediate hypersensitivity, the molecule was contra-indicated and tests for cross-reactivity were conducted. PATIENTS: Three hundred fifty patients were sent to this unit between February 2000 and April 2001 for drug intolerance, mostly with urticaria/angiooedema but in 7 cases with anaphylactic shock. The incriminated drugs were varied: 50 p. 100 were due mainly to penicillins and cephalosporins. Other drug groups were also involved: non steroid anti-inflammatories, aspirin and paracetamol for the most part, along with local anesthetics, morphine-based products, contrast iodine products, corticosteroids. RESULTS: Of the 350 patients tested, only 22 were allergic and had positive tests for the incriminated drug. In these 22 patients, with the exception of 2 of them, the effects were severe (anaphylactic shock in 7 patients) and the urticaria was only a minor manifestation of the reaction. The drugs responsible were cephalosporin (10 patients), the penicillin (6 patients), insulin (2 patients), gonadorelin (1 patient), carboxymethylcellulose (1 patient), lidocain (1 patient), and sulfamethoxazole (1 patient). The 328 other patients had negative tests and were able to retake the tested molecule without incident. Most of them had antecedents of chronic urticaria or dermographism. DISCUSSION: Only 22 patients of the 350, i.e. 6 p. 100 were genuinely allergic. These patients were those who presented the most severe symptoms. The other patients, i.e. the majority, suffered from pseudo-allergic drug-induced urticaria, which made retaking the medicines possible.

[A new tool for evaluation of medication errors applied to pediatric hematology]. / Un nouvel outil d'évaluation de l'iatrogénie médicamenteuse, appliqué à l'hématologie pédiatrique.

This study was conducted in a haematological paediatric department and was aimed at evaluating drug medication errors. Their frequency was studied, but also and mainly their degree of severity and preventability. Only adverse drug events that were identified as possibly due to pharmacological properties of drugs or medication errors were collected. An original method was used, based on a multidimensional mathematical tool, called Factorial Analysis of Multiple Correspondences (FAMC), in order to assess the grade of severity and preventability for each adverse drug event. A total of 155 adverse drug events were detected for 34 out of 52 patients hospitalized during the study period. The prevalence rate was 65 per cent and among these adverse drug events, 16 per cent were serious and 53 per cent were avoidable. Apart from the fact that the FAMC helped to determine the grade of preventability, FAMC allowed one to demonstrate that allergy and medication errors were the most avoidable adverse drug events. In this way the method used was validated. This study permitted the assessment of drug medication errors in this department and helped to choose the priorities for the management of preventive actions.