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In the absence of a therapeutic alternative, the use of neuroleptics in geriatrics should be limited to the bare minimum, given their potentially serious deleterious effects in frail elderly patients. Dyskinesia is one of their most common side effects. Case of an elderly patient in whom the dyskinesia was revealed following abrupt cessation of a neuroleptic taken in the long term with discussions of the etiological hypotheses of this rare situation, which nevertheless deserve to be known., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: The aim of the study was to estimate the cost-effectiveness ratio of aripiprazole once-monthly compared to once-monthly injectable paliperidone palmitate in the treatment of schizophrenia in France on the basis of results and data from the QUALIFY study., Methods: Consumed resources data measured with a dedicated questionnaire and results on the quality of life scales from the QUALIFY study were combined with French standard unit costs of each collected consumed resources during QUALIFY to estimate the cost-effectiveness ratios of the two products. Multivariate sensitivity analyses were performed to test the combined impact of the different assumptions., Results: Findings of the study showed greater efficacy on the quality of life (QLS) and psychiatric evaluation scales (CGI-S and CGI-I) observed in QUALIFY of aripiprazole compared with paliperidone palmitate. Findings also suggest a trend (P=0.0733) in the reduction of total costs linked to a statistical decrease (P<0,0001) in drug costs in the aripiprazole group. These findings are reinforced by the probabilistic sensitivity analyses., Conclusion: Aripiprazole appeared to be more cost-effective than paliperidone palmitate in the French context. Limits of this study are mainly related with the duration of the clinical trial and to assumptions on the transposability of measured consumed resources in the international clinical trial to the French healthcare system., (Copyright © 2018 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

After reminding the various phases of the development of molecules, this article will state the stages of commercialisation of treatments, underlining the FDA (Food and Drug Administration) and the EMA (European Medicine Agency) requirements. Like all the other treatments available in Europe and in the United States, the long acting injectable antipsychotics (LAI) have to prove their efficacy compared to placebo and their non-inferiority compared to a treatment of reference, usually the same molecule in the oral form. These criteria of efficacy have evolved over time. If initially classical criteria of symptomatic intensity (score on scale PANSS) were considered, criteria more adequate from a clinical perspective, such as relapse, but also related to functioning, quality of life and, more recently, costs-effectiveness have appeared. This evolution is probably due to several factors: vision on mental illness, progress in patient's rights and aspirations, but also the pregnant place of health costs recently taken in the evaluation of treatments. These modifications are also based on the indications of L.A.I., i.e. stabilized patients for whom the challenge is rehabilitation care more than the control of symptoms., (© L’Encéphale, Paris, 2016.)

Background: The elderly are particularly vulnerable to the iatrogenic effects of drugs that are a major public health problem. In a geriatric care unit of a psychiatric hospital, the pharmacist, in close cooperation with the various health professionals, takes part in the optimization of drug therapy of these patients during cross-professional consultation meetings. From 2009 to 2011, an evaluation of professional practices was run through a targeted clinical audit on the theme of "prescription drugs at the age of 75 and over". The main objective of this study is to measure the differences between the practices and the guidelines for prescription drugs concerning the elderly, and then to analyze and amend these differences. The secondary objective is to gather data on the prescription drugs for the elderly in the particular context of a psychiatric unit., Methods: The evaluation was performed using two standards: the evaluation chart of prescriptions of the Professional College of French Geriatrics (CPGF) and the French National Authority for Health and the list of Laroche et al. In the first round, after analyzing the prescriptions of 105 patients, the gap between practice and accepted standards led to the definition of three areas of improvement on the associations of neuroleptics, on the use of anticholinergic drugs and on the prescription of benzodiazepines, the latter being subject of another communication. After reassessment, the prescriptions of 101 patients were thereafter analyzed in relation to the identified areas of improvement., Results: Patient samples of both phases were statistically homogeneous. Between the two evaluations, the percentage of prescriptions with at least two neuroleptics remained stable, the decline was not significant (18.1% to 13.9%, P≥0.05). However, it was observed that the second suggested a "conditional" decline with dosages less than or equal to those recommended for the elderly dosages. The proportion of patients who did not take anticholinergic drugs increased from 30% to 60% (P≤0.01). In parallel to the improvement of these criteria, it was noted that the average number of psychotropic drugs prescribed was significantly reduced (from 3.3 to 2.79 psychotropic/patients, P=0.078)., Discussion: The involvement of a pharmacist in cross-professional meetings of a care unit of psychiatry for the elderly has contributed in setting up a clinical audit focused on the drug management of these patients. This work enabled measurement of the progress made in the use of anticholinergic drugs, following the guidelines. In the mean time, it has been highlighted that the standards used are difficult to comply with regarding some criteria. For instance, the use of neuroleptics in the case of elderly patients hospitalized in the unit of psychiatry and not in the unit of geriatrics requires specific adjustments. Indeed, there are patients whose disorders have led to psychiatric hospitalization, which may require a combination of two neuroleptics. This paved the way for us to develop, within a working group representative of all professionals involved, a list fitting our medical practice and integrated into a guidebook adapted to the drug therapy management of elderly patients in psychiatry. The approach being successful, this targeted clinical audit will be extended to patients aged 75 years and over, hospitalized in other care units of the hospital., (Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: There are numerous risk factors involved in poor (incomplete) compliance to pharmacological treatment, and the associated relapse risk, for patients with schizophrenia. Comorbid substance use disorders are considered as among the most important ones, although how much their presence increase the risk of poorer observance (and higher risk of relapse) has not been yet assessed. This measure would be important, especially if the published literature on the topic provides sufficient material to perform a meta-analysis and to assess different potential biases such as those related to time (new studies are easier to publish when positive) or sample size (small samples might drive the global positive conclusion)., Method: A PubMed(®) search was made, screening the following terms between 1996 and august 2014 "Addiction AND (Observance OR Adherence) AND schizophrenia AND (French OR English [Language])" and "(Substance Abuse OR substance dependance) AND Outcome AND schizophrenia AND (French OR English [Language])". Studies were included if they describe two patients groups (schizophrenia with and without present substance use disorder) and assess the studied outcome. MetaWin(®) version 2 was used for the meta-analysis, while publication time bias relied on non-parametric correlation and the one linked to sample size was assessed through normal quantile plots. An attributable risk was also computered, on the basis of the odds-ratio derived from the meta-analysis and the prevalence of the analyzed trait (associated substance use disorder)., Results: Eight studies could be included in the meta-analysis, showing that the presence of a substance use disorder significantly increases the risk of poor observance to pharmacological treatment (OR=2.18 [1.84-2.58]), no significant bias being detected, either linked to time (rho=0.287, P=0.490) or sample size (Kendall's Tau=-0.286, P=0.322). The related attributable risk is 18.50%. Only three studies could be used for the meta-analysis of the risk of relapse associated with the presence of substance use disorders. The corresponding odds-ratio is 1.52 [1.19-1.94], and the attributable risk is 31.20%, but the search for biases could not be performed because of the small number of studies., Conclusions: These results shed light on the importance of comorbid substance use disorder to explain the poor observance frequently observed in patients with schizophrenia. Indeed, having an associated substance use disorder double the risk of poor compliance to pharmacological treatment, this comorbidity explaining a fifth of all factors involved. Although the number of available studies does not allow definite conclusions, the meta-analysis of prospective studies focusing this time of the risk of relapse requiring hospitalization is also in favor of a significant role of associated substance use disorder. These results argue in favor of developing specific strategies to better treat patients with dual diagnoses, i.e. schizophrenia and substance use disorder., (Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic polymorphism of the P450 2D6 cytochrome) and showed that with an injectable sustained release form, a monthly dose of 400mg would allow 90% of patients to gain exposure in the therapeutic range. In case of a drug inhibition and/or of a slow metabolizing profile, dosage adjustment is necessary., (Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Management of agitation is a frequent problematic of emergency departments that often leads to feelings of insecurity among clinicians. There are various practices regarding the drugs to be used in the management of agitations. Guidelines have been proposed by different groups of experts concerning the antipsychotic drugs that should be used for agitations in psychiatric conditions. Nevertheless, there is no clear-cut procedure referring to the utilization of intramuscular drugs in this situation. Moreover, there is no comparison available between the commonly used medications and other drugs, both in terms of superiority of efficacy and tolerance. In order to accurately assess these practices, evaluation protocols must minimize the interference with the service organization and the routine care. Further studies are required in order to develop guidelines about medications that have to be used to handle agitations, which must be based on robust evidence and applicable to emergency services., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Schizophrenia is a debilitating disease that usually begins in young adulthood, at a time when a person would usually make the transition to independent living, but it can occur at any age. The symptoms and behaviour associated with psychosis and schizophrenia have a distressing impact on the individual, and the family. The course of schizophrenia varies considerably. Although most patients will recover, some will have persisting difficulties or remain vulnerable to future episodes. Therefore, stabilisation of patients in acute phases and avoidance of relapse are major objectives of management throughout the course of this disease. The purpose of this article is to clarify the stabilisation, to study the contributing factors and strategies to implement to achieve stability, through a literature review and key guidelines. Thus, the patient is stabilised when productive symptoms and behavioural problems have decreased. So, the stable phase represents a prolonged period of treatment and rehabilitation during which symptoms are under adequate control and the focus is on improving functioning and recovery. Important predictive criteria of stabilisation include: positive symptoms, the number of previous relapses, cooperation with the patient and family, good adherence to treatment and the use of long acting injectable second-generation antipsychotics. After an acute relapse, the careful organization of the discharge and the development of a proposed ambulatory care in tailored care structures will help consolidate stabilisation and obtain remission. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role beside patients and their families. The course of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, identification of prodromes, active information for the therapeutic education of patients and families and access to care will also be supported. This would improve the functional abilities of patients, their social adaptation and particularly their quality of life., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Aim: The aim of the study was to identify and to characterize patients with Alzheimer's disease or related dementia describing antipsychotics and other psychotropic expositions., Methods: The study was performed, in 2010, based on Provence-Alpes-Côte d'Azur region (PACA)-Corse Alz cohort included patients with dementia, with chronic condition 'Alzheimer disease or related disease' and/or had at least one delivery of Alzheimer's specific treatment, registered in the General Health Care System. Psychotropic drugs were extracted according anatomical, therapeutical and chemical code. Chronic exposure defined as more than 3 consecutive deliveries., Results: Among 34 696 included patients, 26.9% were men and 68.8% were 80 years old and more. Among them, 26% received at least one antipsychotic medication, with a chronic exposition estimated around 61.3%. Antidepressant and anxiolytic were consumed respectively by 47% and 45.3% of patients. Risperidone was the most used antipsychotic (11.2%). The Health care use (hospitalizations, nurses and physicians visits) was significantly higher among patients with antipsychotics., Conclusion: Antipsychotics use in patients with dementia remains high. The follow up of this regional cohort would be helpful to identify the impact of guidelines on the prescription and the care of patients with dementia., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Background: Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice., Methods: The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia., Results: LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors., Conclusion: A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed., (Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Psychiatric disorders may complicate the pregnancy and is one of the causes of maternal and fetal morbidity. We report the case of a patient with severe decompensated schizophrenia during her pregnancy that required prolonged hospitalization in psychiatric ward. The psychiatric status of the patient required the realization of a caesarean section at 36 weeks of amenorrhea. In our case, we decided to perform this cesarean section under general anaesthesia, since regional anaesthesia was not feasible in this patient in a state of uncontrolled agitation. Moreover, general anaesthesia permitted to combine cesarean section with a first session of electroconvulsive therapy, which had been declined during pregnancy. Given the huge amount of antipsychotic agents administered to the patient, we also studied their transplacental transfer and found a very high loxapine concentration in the fetus. Finally, this case raised several important ethical issues related to the management of the mother and her fetus in case of severe psychiatric disorders., (Copyright © 2013. Published by Elsevier SAS.)

The current review raises the question of the place of long-acting injectable (LAI) atypical antipsychotics for the treatment of first-episode schizophrenia in current and future guidelines. After exposing the different points of view adopted in the former, the author presents the clinical trials conducted with LAI atypicals in this indication, as well as the surveys related to psychiatrists'opinion regarding the use of these drugs in early schizophrenia. Pros and cons of this therapeutic option are discussed and suggestions are made for further guidelines., (Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: The objectives were to assess the characteristics of patients with bipolar disorder (BD) and to evaluate the prescribing practices., Methods: MONTRA is a quantitative survey conducted between December 2010 and February 2011. Data were extracted by the psychiatrists from the medical files of BD patients seen on four consecutive days of consulting., Results: Four hundred and thirty-nine psychiatrists included 2529 patients (inpatients, n=319; outpatients from mental clinics, n=1090; outpatients consulting in private practice, n=1020). In the total patient population (mean age: 47 years; women, 58%), BD was distributed as follows: BD type I, 56%; BD type II, 40%; other types of BD, 4%; rapid cyclers, 10%. The prevalence of psychiatric comorbidities was high (anxiety disorders, 48%; abuse and dependence on toxic substances, 17 and 10% respectively), 36% of the patients had a history of suicide attempt and the risk of suicide, when assessed, was 6%. In about half the patients (48%), the polarity of the initial bipolar episode was of the depressive type (versus 39% for the manic/hypomanic type). Outpatients were globally independent and did not require assistance in the management of their disease or its treatment whereas the social and professional lives of inpatients were negatively affected by their condition. Based on the psychiatrist's declarations, 39 to 50% of the outpatients were symptom-free, 36 to 40% were in the intercurrent phase with residual symptoms, 11 to 17% presented either a manic or depressive acute BP episode, and 3 to 4% were in a mixed state; among inpatients, 52% presented an acute episode either manic or depressive, 38% were in the intercurrent phase and 9% were in a mixed state. In the symptomatic patients from the total population (61%), the most prevalent symptoms were depressive and corresponded to acute symptoms (patients with a depressive episode, 14%) or residual symptoms (patients in the intercurrent phase, 27%). The predominant depressive polarity was observed in both hospitalized and outpatients. The pharmacological treatment of BD included polytherapy in 73% of the patients. In the manic episodes (n=126), the patients were treated with a Mood Stabilizer (MS, 56%) or an atypical antipsychotic (AAP, 52%) in association. In the depressive episodes (n=342), the patients received an antidepressant drug associated with a MS or an AAP (70%). In symptom-free or symptomatic intercurrent periods (n=1943), the patients were treated with a MS (49-58%) or an AAP (37-49%), in association., Conclusion: BD patients evaluated in our survey were in majority diagnosed with BD type I, associated with considerable comorbidity. In the symptomatic patients, the most prevalent symptoms, either acute or residual, were of the depressive type. In the majority of the patients, whatever the clinical status, polytherapy was prescribed for the BD., (Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Poor adherence is a major concern for the effectiveness of antipsychotic treatment in patients with schizophrenia. In particular, compliance problems constitute a poor prognostic factor for this disorder due to increasing risk of relapse and hospitalization. As maintaining antipsychotic therapy is a key element to prevent relapse, the use of depot preparations is therefore considered as a useful therapeutic option since it prevents covert non-adherence. When compared with neuroleptics, novel antipsychotic agents are also better tolerated by patients. In this study, the rationale for the use of long-acting injectable risperidone combining the benefits of novel antipsychotic agent and depot preparation is investigated in patients with psychosis. A secondary objective of the study is to assess the level of therapeutic adherence and to confirm the role of its key determinants., Methods: An observational survey assessed the time and reasons to switch to long-acting risperidone in 1887 hospitalized and community-dwelling patients with psychosis (61.6% schizophrenia) defined by the CIM-10, and treated by 399 psychiatrists with oral risperidone for a recent acute episode. In a cross-sectional study performed under real-life conditions, treatment adherence was assessed by patients themselves using the Medication Adherence Questionnaire (MAQ) and therapeutic alliance was assessed by the 4-Point Alliance Scale (4-PAS). Psychiatrists assessed treatment acceptance using the Compliance Rating Scale (CRS), disease severity using the CGI, and insight using the G12 item from the Positive and Negative Syndrome Scale (PANSS)., Results: In the population studied, disorder severity (CGI) was defined as "moderate to marked" in 67.7% and "severe or among the most severe" for 21.1%. Insight (PANSS G12) was defined as normal for 36.6% of patients, moderate for 34.8% and low for 28.6%. The mean time to medication switch was 8 weeks after the start of care of the acute episode. The two main reasons to start the long-acting injectable risperidone were related to non-compliance with oral antipsychotic treatment (92.4%) and intention to improve efficacy (86.4%). Maintenance of a good therapeutic alliance (70.3%) and treatment tolerability (54.6%) were also often cited. For psychiatrists, 41.6% of patients demonstrated reticence or active reluctance to treatment. Therapeutic compliance (MAQ) for oral medication before the long-acting injectable risperidone was started was estimated as "mild" for 53.1% (n=852) of patients. Poor adherence strongly correlated with low insight (P<0.001) and with a disorder estimated as "severe" (P<0.001). Therapeutic alliance was higher for patients with a better level of treatment acceptance assessed by psychiatrists (P<0.001) and with a higher compliance with MAQ estimated by patients (P<0.001). Therapeutic alliance was lower for patients with a disorder defined as "severe" (P<0.001) and with poor insight (P<0.001)., Conclusion: In this French survey, the two main reasons for psychiatrists to start long-acting injectable risperidone were related to non-compliance with oral antipsychotic treatment and with the desire to improve therapeutic efficacy. In accordance with results of previous studies, insight and therapeutic alliance were found to be associated with poor compliance. The main goal in the treatment of psychotic disorders is to obtain a functional remission and to reduce the incidence of relapse. Considering its improved efficiency and reduced dependence on patient compliance, the use of long-acting injectable risperidone is recommended as a useful therapeutic strategy., (Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Dysphagia is a common symptom in the general population, and even more among psychiatric patients, but rarely seen as a sign of seriousness. It is a cause of death by suffocation, and more or less serious complications, and therefore should be diagnosed and treated. Among psychiatric patients, organic and iatrogenic aetiologies, as well as risk factors are identified, which worsen this symptom when associated. It is now accepted that neuroleptics can aggravate or cause dysphagia. They act by several pathophysiological ways on the different components of swallowing, which can be identified by dynamic tests in the upper aerodigestive tract endoscopy., Literature Findings: This symptom is rarely reported by patients and often underestimated by caregivers. The frequency of swallowing disorders is not known. Dysphagia is a cause of complications and an increase in mortality rates among psychiatric patients. It has also been found that the average number of psychotropic drugs in patients who die by cafe coronary is significantly higher than in other patients. There are several phases in swallowing: oral, pharyngeal, and oesophageal. Swallowing disorders can affect each of these phases, or several at once: (a) Extrapyramidal syndrome: dysphagia is present in drug induced Parkinson's syndromes, but prevalence is not known. It is most often associated with another symptom of the extrapyramidal syndrome, but can also be isolated, making its diagnosis more difficult. Dysphagia is due to a slowing down in the oral and pharyngeal reflex, called bradykinesia; (b) Tardive dyskinesia: the oro-pharyngo-oesophageal dyskinesia is the most common type. Oesophageal dyskinesia causes asynchronous and random movements of the oesophagus, resulting in dysphagia. It appears mostly beyond 3 months of treatment with neuroleptics; (c) Acute laryngeal or oesophageal dystonia, associated or not with orofacial dystonia, is characterised by an impairment in the oesophageal muscle contraction and a hypertonia of the upper sphincter of the oesophagus; (d) Polyphagia or "binge eating", is frequent in psychotic patients; (e) Finally, there are risk factors for dysphagia: xerostomia, poor dental status, advanced age, neurological diseases, polypharmacy, sedative drugs, CNS depression, etc., which worsen the symptom., Case Report: Mr J., aged 28, with no psychiatric history, is admitted to the Unit for Difficult Patients in Villejuif for behavioural disorder with homicide on the street. The patient was restrained by passers-by and suffers a head injury and a fracture of the transverse process of L1 vertebra. A cranial CT scan is performed in the emergency room, it is normal. The patient is not known to psychiatric services, and has never taken neuroleptics. Mr J. is homeless, known in his neighbourhood for "his noisy delirium on the street and repeated alcohol abuse." After being arrested by the police in this context, a first psychiatric examination is conducted. The medical certificate states that his condition is not compatible with custody. Mr J. remains mute; he has stereotyped gestures and strange attitudes. No delusion is verbalized. He receives vials of loxapine 50mg causing sedation. At his arrival in the department, Mr J. has the same clinical picture, with a rigid and inexpressive face, reluctance, major unconformity, poor speech. The search for drugs in urine is positive for cannabis. The diagnosis of schizophrenia is rapidly raised, motivating further prescription of loxapine 300 mg daily in combination with clonazepam 6 mg daily. From the earliest days, dysphagia to solids with choking and regurgitation is noted, aggravated by the increase of loxapine treatment of 450 mg / day to 700 mg / day, 7 days after admission. A physical examination is performed before the worsening of dysphagia, it is normal, and in particular, reveals no extrapyramidal syndrome. An anti-cholinergic corrector is introduced, without clinical improvement. A new physical examination is performed; it is normal except for sedation and a slight deviation of the uvula. Upper gastrointestinal endoscopy shows no anatomical lesion. No functional assessment of swallowing is done however. At this stage, the suspicion of neuroleptic induced dysphagia appears to be the most likely hypothesis. Treatment with loxapine is then stopped, resulting in a very rapid clinical improvement. Aripiprazole 15 mg / d is introduced. Dysphagia does not reoccur., Discussion: Loxapine is an atypical antipsychotic, with a lower risk of neurological side effects than first generation of antipsychotics. These side effects are however numerous and from diverse pathophysiological mechanisms. Loxapine is an antagonist of dopamine and serotonin which is involved in the regulation of several neurotransmitters, explaining the multiple mechanisms involved in the onset of dysphagia: first, blocking dopamine D2 receptors in the striatum, causing motor side-effects of central origin, in addition to peripheral effects of the molecule, which impairs swallowing. In principle, the antagonist activity on serotonin 5-HT2A receptors increases dopaminergic activity in the striatum, reducing the risk of extrapyramidal symptoms and tardive dyskinesia, without avoiding them completely. In addition to these mechanisms, cholinergic blockade reduces oesophageal mobility and pharyngeal reflex. Moreover, the antihistamine, anti-cholinergic and adrenergic receptor blocking alpha-1 can cause sedation, which aggravates the symptom. Finally, the depression of the bulbar centres reduces the swallowing reflex and gag reflex altering the intake of food., Conclusions: The swallowing disorder caused by neuroleptics may occur regardless of the molecule or drug class to which it belongs. It can be found even in the absence of any other neurological signs. It is important to search for the aetiological diagnosis for treatment. At the crossroads of several specialties, swallowing disorders are difficult to diagnose and treat. They are frequently underestimated, partly because patients rarely complain. In our case report, the diagnosis was ascertained by the removal of the medication, without functional evidence, probably by a lack of collaboration between the physician and the endoscopist who had not performed any dynamic investigation of swallowing. This case illustrates the importance of knowing the different mechanisms underlying dysphagia in psychiatric patients, and good communication with gastroenterologists to establish a precise diagnosis of the disorder, and adapt the therapy., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

An accurate treatment of first episodes in schizophrenia and bipolar disorders has a significant impact on compliance and prognosis. However, existing therapeutic guidelines may be poorly respected and may concern only typical clinical situations. Medical attitudes in clinical practice have been collected and structured on the basis of small interactive meetings (Focus Group [FG]), and a synthesis of practical attitudes has been compared with updated guidelines. The FG method applied to treatment initiation in schizophrenia and bipolar disorder is seen as complementary to evidence-based guidelines. It reveals that, in a reflexive manner, clinical attitudes are often more diverse and frequently consider first treatments after global evaluation, taking more into account external factors such as clinicians' experience, patient's history and willingness, clinical setting, and environment. A symptomatic approach is sometimes preferred, and a better alliance is always considered as a main objective. The FG method could be a supplementary support to continuous medical education., (Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Psychiatric disorders appear to be frequent in patients with diabetes mellitus. The presence of psychiatric co-morbidity may affect adherence to medication and self-care regimes., Aim: To establish rules of the management of diabetes among people with psychiatric disorders., Methods: Literature review on the PUBMED database using the following keywords: diabetes, psychiatric disorders, anti-psychotics, complications., Results: Psychiatric disorders appear to be frequent in patients with diabetes mellitus. Their presence is associated with poor glycemic control and more diabetes complications. This negative effect may be increased by taking atypical antipsychotics which expose to several metabolic effects such as overweight, insulin resistance, hyperglycemia, Type 2 diabetes and dyslipidemia., Conclusion: The management of diabetes among people with psychiatric disorders should be multidisciplinary including internist, diabetologist, psychiatrist, and paramedical staff. This treatment includes medical (anti-diabetics, anti-psychotics) and psychotherapeutic interventions through which we can have better glycemic control and decreased rates of diabetes complications.

Unlabelled: Despite the advantages of antipsychotic treatments via the injectable route of administration, there are still reservations regarding this type of therapy, notably among health professionals. A survey conducted with patients suffering from schizophrenic disorders revealed the positive opinion that they had of their treatment. Another survey showed that nearly half of the patients preferred an injectable form, and two thirds felt they were cared for better, because of the injectable treatment. The slow release form of risperidone allows a choice between two injection sites: the deltoid muscle or the gluteal muscle. A recent study showed the satisfaction of the health professionals towards this novel form. The survey presented here was aimed at collecting the opinion of patients regarding the possibility of choosing the injection site, and the changes it would make., Objectives and Methods: The survey was carried out by the BVA Institute during the first half of 2011. The interviews with the schizophrenic patients, followed-up as out patients and treated with long lasting antipsychotics (n=281), were conducted face to face at the hospital by BVA interviewers specialised in the field of health, without the presence of any health professionals. A total of 32 centres participated in the survey; 38% of the interviews took place in the Paris area and 62% in various regions., Results: Different dimensions were analysed. (1) The perception of injectable treatment was largely positive: among all the patients, 75% claimed they currently felt better once they had started the injectable treatment. (2) The choice of the injection site appeared important to a majority of patients (70% of the total sample; 79% of patients had experienced both sites of injection), 56% claimed that it was legitimate that they be given the choice and they felt that they were thus able to participate in their treatment (58%), their treatment was more acceptable (54%), and they found that their relationship with the doctor or nurse was enhanced (53%). (3) The preference regarding the injection site went to the deltoid muscle, among those who had experienced both sites. (4) The perception of the injection sites confirms this preference, the positive qualifications often being associated with the deltoid site, and the negative qualifications with the gluteal site., Conclusion: The survey presented here could contribute in convincing the health professionals to propose the choice to patients between the two injection sites in order to improve their compliance to treatment. Patients would therefore play a role in the choice of their treatment and hence become more involved in the follow-up., (Copyright © 2012. Published by Elsevier Masson SAS.)

Objective: To present points of agreement and disagreement about antipsychotics. Since the appearance of 2nd generation long-acting antipsychotics (LAA), and given the high frequency of noncompliance with antipsychotics in psychotic disorders, LAAs have attracted more interest in psychiatric literature. However,their use is suboptimal, globally, and is also subject to significant national disparities. ln this context,the Association des médecins psychiatres du Québec (AMPQ) has asked for a review of the evidence concerning LAA efficiency and tolerance, and has called for consensual c1inical reflection on the benefits and obstacles of prescribing them, as weil as potential solutions, including administrative and judiciary dimensions., Methods: The AMPQ established an expert committee, from 4 Quebec universities, which was responsible for preparing the review paper. The committee intended to appropriately provide c1inicians with the different aspects of LAA use. The committee produced a qualitative and selective review., Results: Mean LAA prescription rates observed in Canada are around 6% and data to confirm this are scarce. A 15% to 25% rate could be suggested., Conclusion: The committee has submitted the Quebec long-acting antipsychotic algorithm (QAAPAPLE, derived from the French acronym) as a result of the consensus reached by the 4 university psychiatry departments.

Introduction: Schizophrenia and its related disorders are prevalent, disabling and costly. Recent longitudinal studies found that the first two to five years of schizophrenia-spectrum disorders are characterised by symptomatic and functional deterioration. This led to the hypothesis of the existence of a critical period in the treatment of individuals suffering from psychosis: an assertive intervention during the first two to five years of psychosis could improve long term outcomes and prevent the emergence of psychosocial deficits., Objectives: The objectives of this review are to describe different specialised first-episode psychosis services (FEP) and report their results at different times of follow-up in order to determine what specific approaches they should include, the optimal duration of treatment, and the characteristics of the patients who benefit the most from such programs., Method: We systematically reviewed psycINFO and MEDLINE in search of studies dealing with efficacy or efficiency of specialized FEP programs. We only included research that had at least one comparison group and excluded those dealing with primary prevention of psychosis or prodromal interventions., Results: Five, all Scandinavian, programs and their results at different follow-up times are presented. The Parachute project started in 1994 in Sweden with the objectives to use low dosages of antipsychotics (AP), to minimize hospitalisations, to offer specialized individual and familial psychotherapy, and to assure continuity of care during a five-year period. It compared the Parachute study group with a prospective and a historical group. At three years, the Parachute group had spent less days hospitalised (but more days in a crisis home), was associated with a lower percentage of patients receiving disability allowances and had a trend toward better efficiency than the control groups. The Danish National schizophrenia project started in 1997 and included 16 centers that offered a two-year specialised FEP treatment. Patients were randomly assigned to treatment as usual (TU), treatment as usual enriched with support psychodynamic psychotherapy (SPP) and integrated treatment (IT). At the end of the two-year treatment period, patients receiving IT had significantly less positive symptoms, less negative symptoms and better scores in the global assessment scale (GAS) than TU. The Opus project started in 1998 in Denmark. It is a randomised, controlled study comparing a two-year FEP integrated treatment (IT) with standard treatment (ST). After the two-year period, patients were transferred to ST and were assessed at five years (three years after the end of the IT). At the end of the active phase of treatment, patients in IT group had better positive, negative and GAS scores, used lower dosages of AP and used less illicit drugs. At five-years, the only difference between IT and ST groups was that the IT group was associated with more patients living independently. The Open Dialogue project started in 1994 in Finland. It compared conventional treatment (CT) with acute psychosis integrated treatment (API) and Open dialogue approach in acute psychosis treatment (ODAP). At the two-year assessment, API and ODAP groups had less relapses, spent less days hospitalised, used less AP and had better GAS scores than CT. The ODAP group had better scores on the brief psychiatric rating scale than the API group and was associated with fewer patients receiving disability allowances than the CT group. At five-years, there was no difference in the outcomes between API and ODAP, but the authors suggest that the ODAP group was more efficient, because it had similar results as the API group while using less resources. The Soteria Nacka project started in 1990 in Sweden. It compared patients receiving only outpatient specialised FEP treatment (CE) with those receiving outpatient and crisis home specialised FEP treatment (CC). At the five-year assessment, the CC group had better GAS scores than the CE group, but only for patients suffering from a psychosis in the schizophrenia-spectrum. Also, less patients in the CC group used AP and when they did, they had lower dosages. The CC group was also associated with more patients working or studying at the end of the five-year follow-up and with significantly more patients in remission compared to the CE group. Finally, the Opus project, Parachute project and Soteria Nacka found that patients suffering from a psychosis in the schizophrenia-spectrum are those who benefit the most from the specialized, comprehensive, FEP-programs., Conclusion: The programs specialised in the treatment of FEP show encouraging results mainly during their active phase. This review suggests that a two-year treatment period is not long enough to enable patients to maintain the improvements obtained during the active phase of an integrated treatment. Future studies should aim to determine--the characteristics of the patients that most benefit from--the specific interventions that should be included in and--the ideal duration of treatment of the comprehensive FEP programs., (Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Anxiety is a major and frequent symptom of schizophrenia, which is associated with an increased risk of relapse, impaired functioning, lower quality of life and increased incidence of suicide attempts. Despite its clinical relevance, anxiety in schizophrenia remains poorly understood. In the prodromic phase, anxiety indicates a progression towards psychotic decompensation. After a first episode, it is an indicator of relapse., Literature Findings: Two approaches have been used to investigate anxiety in schizophrenia: (i) categorical approach (comorbidity of schizophrenia and anxiety disorders) and (ii) dimensional approach (anxiety as a major symptom of the "dysphoric" dimension). Clinical categorical studies reported an increased frequency of comorbidity between schizophrenia and obsessive-compulsive disorder, panic disorder, social phobia, post-traumatic stress disorder, generalized anxiety disorder, agoraphobia, and specific phobia. The dimensional approach proposes that five different factors contribute to the structure of the Positive and Negative Syndrome Scale (PANSS), with anxiety as a major symptom of the "dysphoria" dimension. Concerning diagnosis, it is unclear whether psychotic and neurotic anxiety differs in nature or intensity. Nevertheless, both are frequently opposed., Discussion: Psychotic anxiety is intense, profound and hermetic. In contrast to neurotic anxiety, it is associated with psychomotor disturbances, such as agitation and sideration. There is no specific tool to evaluate anxiety in schizophrenia. The dimensional approach usually runs an evaluation using items or factors extracted from the most widely-used scales, i.e. PANSS or Brief Psychiatric Rating Scale (BPRS) or from anxiety scales developed in non-schizophrenic populations, such as the Hamilton Anxiety Scale (HAMA). Recently, we developed a specific scale for hetero-evaluation (Échelle Anxiété Schizophrénie [EAS scale]). The EAS scale was recently validated and the study of its sensitivity is ongoing. THERAPEUTICAL ISSUES: Several studies have examined the effects of antipsychotics on the anxious/depressive cluster extracted from the PANSS, and some other studies have specifically evaluated the effect of antipsychotics on depressive symptoms using the Montgomery and Asberg Depression Rating Scale (MADRS) and Calgary Depression Scale for Schizophrenia (CDSS), but to our knowledge, no study has reported the effect of antipsychotics or other treatment on anxiety when using a schizophrenia-specific scale. There are no specific guideline treatments for anxiety in schizophrenia. Among phenothiazines, cyamemazine is frequently prescribed in France, because of its potent anxiolytic activity and good neurological tolerance. Some authors have suggested a specific treatment with benzodiazepines. However, benzodiazepines should be used with caution, due to undesirable actions such as dependence, rebound and potentiation of certain lateral effects., (Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: the quality of life of patients suffering from schizophrenia was extensively studied but it seems that impact on quality of life of neuroleptics, particularly atypical antipsychotic treatment was not clearly elucidated., Aims: In this study we have compared the impact on quality of life of atypical antipsychotic versus classic neuroleptics., Methods: We have enrolled, prospectively, all patients with schizophrenia as confirmed by DSM-IV TR. These patients intakes antipsychotics for unless 6 months. We excluded patients with acute schizophrenia, mental deficiency and severe organic disease. Evaluation of clinical features is based on the PANSS scale (Positive And Negative Syndrome Scale). The quality of life is evaluated using the MOS-SF36 scale (Medical Outcomes Study 36-item Short Form). Extra pyramidal symptoms were evaluated by the Chouinard scale., Results: We have enrolled 65 patients; 35 under classic neuroleptics and 30 under atypical antipsychotics. Clinical features were similar in the two groups. Patients with atypical antipsychotics were less hospitalized (2.4 +/- 3.2 vs. 4.5 +/- 4.2; p = 0.02) and needing less anti cholinergic treatment (26.6% vs. 88.6%; p < 0.0001). Adverse effects were more common with classic neuroleptics (Pakinsonism score: 6.1 +/- 7 vs. 10.8 +/- 8.6; P = 0.01); global clinical dyskinesia 1.22 +/- 0.8 vs. 1.90 +/- 1.7; p = 0.04; global clinical judgement of parkinsonism (2.41 +/- 2.1 vs. 3.72 +/- 2.4; p = 0.02). Quality of life was better in patients with atypical antipsychotics on the basis of vitality (76.7 +/- 27.8 vs. 62 +/- 29.6; p = 0.04) and social function (53.3 +/- 33 vs. 36.9 +/- 27.5; p = 0.03) we found a negative correlation between adverse effects and quality of life in patients with classic neuroleptics., Conclusion: Quality of life of patients suffering from schizophrenia with atypical antipsychotics is better than in those with classic neuroleptics and this may be due to the frequency of adverse effects particularly extra pyramidal symptoms.

Introduction: The necessary evidence of new therapies of clinical interest extends beyond clinical trials in a less controlled population and closer to clinical practice justified since several years the need of conducting observational, noninterventional studies. Observational studies must include epidemiological (quantitative observational) data to define prevalence and natural history of the target conditions. Moreover, pharmacological interventions in "naturalistic" patients populations, selected by clinicians as per clinical judgment within the scope of the target disease will allow to generate data to complement clinical trials. Clinical trials designed to show robust data on efficacy and tolerability particularly during registration trials must be complemented by robust observational research to confirm and better describe clinical effectiveness in the target population. A noninterventional, observational trial is a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorization. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnosis or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data. Olanzapine is a new antipsychotic therapy registered in Europe for the treatment of schizophrenia since 1996., Aims of the Study: The primary objective of this observational research was to study the evolution of the olanzapine dosage under naturalistic settings. Secondary objectives included patients characteristics, severity of disease, therapeutic evolution and coprescriptions, in a patient's cohort, suffering from schizophrenia, adult patients, diagnosis based on ICD-10; patients were followed during a total of 12 months., Design of the Study: The cohort study was conducted in France. Between the period of June 2000 and February 2001, 407 psychiatrics randomized to participate in the study had consolidated the patient's cohort., Results: A total of 1810 patients were included, 1093 (60, 4%) male, 717 (39, 6%) females. Age was recorded for a total of 1802 (99, 6%) patients, mean age was 37.8 years as per inclusion criteria and patients consent according to current regulations. Patients entered in the cohort as per clinicians decision underwent a treatment with olanzapine during an outpatient's consultation or at hospitalization. More than two thirds of the patients were followed up during 12 months after onset of this treatment. Clinical outcome was assessed at three, six, nine and 12 months following cohort inclusion using the following tools: CGI, PANSS, Calgary and GAF; as per CGI 78% of the patients cohort were severely ill, the mean PANSS score was 94.1. At second month of treatment clinicians were requested to very well document any changes in olanzapine dosage as well as reasons for the dosage modifications and potential coprescriptions., Discussion: The daily mean dosage of olanzapine was 9.5mg at initiation of treatment, 10.5mg after one month and 11.2mg after 12 months of follow-up. The increase of the dosage after one month was associated with factors such as younger age, schizophrenia diagnosis and severity of the symptoms as measured by CGI and PANSS scores evolution, low initial dosage and hospitalization at treatment initiation. Within the 1810 participants included in the cohort, 1383 (76.5%) received a coprescrition of a psychotropic, for example, 811 (44.8%) a benzodiazepine, 506 (28.0%) an antidepressant. Among the patients cohort that were followed during 12 months, all the clinical and patient-functioning indicators progressed in the direction of a significant improvement.