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In this paper, we report the case of a patient, aged 26, with schizophrenia who was admitted to psychiatric emergencies for catatonia, one week after abrupt discontinuation of clozapine. An improvement was seen after only two days of the reintroduction of clozapine alone. This catatonia is reversible and it responds magnificently to the reintroduction of clozapine. And we conclude that patients and their caregivers need to be educated about the effects of abrupt cessation of clozapine administration., (Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Tardive dyskinesia (TD) is a movement disorder of tongue, jawbone, trunk and/or limbs that may appear after a prolonged use of dopamine receptor blocking agents (after 3 months of treatment or after 1 month for patients over 60), and that are present during at least four consecutive weeks. TD is a frequent side effect of both classical neuroleptics and new generation antipsychotic drugs. The prevalence of iatrogenic TD is between 24 and 32 % after treatment with classical neuroleptics and about 13 % after treatment with a new generation antipsychotic., Objective: This paper presents an updated literature review of data on diagnosis, prevention and treatment of TD., Methods: We conducted a review of literature using the Medline Browser tool, screening studies from 1950 to 2013 in English or French with keywords « tardive dyskinesia », « tardive dystonia », and « abnormal movements caused by antipsychotic drugs »., Results: We first describe and define semeiological features of TD: dystonia, tremor, myoclonus, acathisie, chorea, ballism and athetosia. Secondarily, we resume the main differential diagnoses to exclude when confronted with this kind of movement disorders. Differential diagnoses for dyskinesia can be classified between primary (Parkinson and Huntington diseases) and secondary (Wilson disease, intoxication, metabolic abnormality, cerebrovascular accident) abnormal movements. Psychogenic TD can be evocated if previous pathologies are excluded in case of atypical clinical presentation. We detail the risk factors for TD. Endogenous risk factors are related to the patient's age, underlying psychiatric disease (bipolar disorder or Alzheimer dementia), addiction to alcohol or cocaine, female gender, or neurodevelopmental vulnerability. Iatrogenic risk factors are high doses of antipsychotics, long or intermittent administration, and particular pharmaceutical classes or associations of antipsychotics. As a comprehensive tool, we review the main physiopathological hypotheses to explain the occurrence of TD in some patients: hypersensitivity of D2 neuronal receptor or neurotoxicity associated with oxidative stress mechanisms. We also summarize the current guidelines for prevention and treatment of TD. Three successive curative strategies are suggested in the literature. First, the clinician can adapt the current antipsychotic treatment (switch to a new generation antipsychotic, diminution or cessation of antipsychotic drugs). If this first intervention is not pertinent or ineffective, the clinician can prescribe an antikinetic therapeutic agent, such as tetrabenazine, or an antioxidant. Review of the published studies does not show proof of efficacy of cholinergic or anticholinergic drugs, benzodiazepine or other GABAergic drugs, nor for amantadine. Non-medication therapeutics such as ECT and TMS are discussed, but the level of proof is insufficient to promote them as a curative treatment for TD. In case of high resistance and discomfort for the patient, a neurosurgical intervention should be discussed. These curative interventions are limited, emphasising the importance of TD prevention, by limiting the prescription and doses of antipsychotics, regularly evaluating their side effects and informing the patient of TD's risk., Conclusion: We propose to practitioners a synthesised update of literature concerning a frequent iatrogenic effect of antipsychotics. Nevertheless, no solid guidelines have as yet been established, and further clinical studies are expected in order to better understand this frequent and discomforting side effect., (Copyright © 2015 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

The robust and specific associations between cognitive abilities and the functional prognosis of patients suffering from schizophrenia lead to a major concern for cognitive impairment in this disorder. Among the strategies considered to correct or enhance cognition in schizophrenia, drugs hold a pivotal place. Evidently, antipsychotic drugs, which are inextricable from patients' management, have generated considerable scrutiny in this topic. This paper first aims to outline the current views on the impact of antipsychotic drugs in schizophrenia. The distinction between conventional and atypical drugs is reminded in order to more precisely review existing data comparing the impact of these two types of molecules on cognitive impairment. More specifically, an elementary framework is proposed to facilitate the recognition of methodological flaws and offer a critical examination of previous findings. It emerges subsequently that differences between atypical and conventional drugs appear far less contrasted than initially suggested. Also, atypical antipsychotics compose a disparate pharmacological class and much clarification could be obtained by differentiating the individual effects of these molecules rather than considering them as a group. Finally, the relevance of these cognitive measures is also considered. In particular, we address alternative measures closer to real life situations as well as the growing interest in the broad field of social cognition. A last part of this article deals with strategies relying on adjunctive therapies. The fairly modest results obtained with these approaches is evoked and briefly reviewed., (Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Management of bipolar disorder has undergone many revisions in recent years as new agents and treatments have been developed and studied with variable success. In conjunction with the advent of novel therapies and indications, there has been an increase in the understanding of the phenomenology and neurobiology of bipolar disorder that has made the classification and management of the illness necessarily more sophisticated. However, there remains a significant delay of 8 years in detecting and diagnosing bipolar disorder, and a further need to improve treatments. However, this paper has emphasized the need to be aware of recent advances and the emerging uses of new pharmacological treatments in the management of bipolar disorder. It has also highlighted the need for tailoring management to the individual. In particular, the successful treatment of bipolar disorder requires achieving prophylaxis and preventing relapse. In this regard, maintenance therapy is of paramount importance, and thus the tolerability of agents needs to be considered throughout treatment and should be factored into all management decisions. At the centre is the individual with bipolar disorder and the need to maintain a healthy therapeutic relationship. However, it is important to note that the evidence synthesized in this paper serves only as a guide to the management of bipolar disorder and that, in clinical practice, all treatment recommendations require contextual interpretation, the consideration of local factors and the consultation of additional resources., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Catatonia and neuroleptic malignant syndrome are both conditions that can compromise survival and whose successful treatment depends on early diagnosis., Objective: Distinguishing between these two conditions is difficult in a clinical setting and is further complicated by diagnostic criteria overlap. Are they both variations of a single disorder or two distinct conditions that happen to share certain characteristics? The goal of this paper is to review the available published data concerning the existence of a link between these two conditions and to specify the nature of the link between them., Method: We identified relevant articles from the PubMed registry by cross-referencing "catatonia" and "neuroleptic malignant syndrome". The articles returned were selected according to language (English and French) and publication date (before November 2007)., Results: Opinions are clearly divided concerning the existence of a link between these two conditions. The most commonly held opinion is that catatonia and neuroleptic malignant syndrome are two entities on the same spectrum. There are, however, no less than five different hypotheses concerning the nature of the link between them: first hypothesis: neuroleptic malignant syndrome is a drug-induced form of catatonia; second hypothesis: neuroleptic malignant syndrome is a drug-induced form of malignant catatonia; third hypothesis: neuroleptic malignant syndrome and malignant catatonia are one and the same; fourth hypothesis: catatonia is a risk factor for neuroleptic malignant syndrome; fifth hypothesis: neuroleptic malignant syndrome is a heterogeneous syndrome that includes both catatonic and non-catatonic responses to antipsychotic drugs. Other research maintains that catatonia and neuroleptic malignant syndrome are two distinct conditions. This point of view has fewer proponents, but benefits from historical, clinical and neurobiological studies that comfort this hypothesis. A careful clinical examination should in theory enable the distinction between these two entities and various neurobiological hypotheses are put forward to explain the differences between them. ANALYSIS AND DISCUSSION: The analysis of the data does not enable the elaboration of a single consensus on the existence of a link between catatonia and neuroleptic malignant syndrome. Additionally, the different hypotheses' level of scientific proof is insufficient to confirm or reject them. We only have at our disposal isolated case studies or studies with varying diagnostic criteria., Conclusion: A review of the literature does not enable us to confirm or invalidate a link between catatonia and neuroleptic malignant syndrome. However, answering this question would have direct consequences, since the suggestion of a link has led to the contraindication of neuroleptics for the treatment of catatonia, which contraindication has been extended on principle to the use of all newer antipsychotic medication. But since the link between catatonia and neuroleptic malignant syndrome has not been established according to scientific criteria, should the contraindication of atypical antipsychotic drugs be maintained in the treatment of catatonia?, (2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Child and adolescent catatonia has been poorly investigated. Moreover, diagnosis criteria only exist for adult psychiatry, and there are no therapeutic guidelines. The aim of this paper is to describe the case of a 14-year-old girl presenting an overlap between psychogenic and neuroleptic induced catatonia, acute treatment and ten year's follow-up., Case Report: A 14-year-old Caucasian French girl, Elsa, was admitted in February 1998 to a University adolescent mental health center with an acute psychotic disorder. She showed agitation, impulsivity (sudden engagement in inappropriate behaviour), paranoid delusions, visual and auditory hallucinations, diurnal and nocturnal urinary incontinence, lack of self-care, inadequate food intake because of fear of poisoning, and vomiting after meals leading to rapid weight loss of 5 kg. Clinical examination, laboratory tests, EEG and RMI were normal. Toxicological tests were negative. Her IQ, assessed six months before admission, was in the dull average range (70-75). Elsa was treated with loxapine 150 mg per day for one week without improvement and this was then replaced by haloperidol 30 mg per day. One week after the start of haloperidol her agitation, impulsivity, and hallucinatory symptoms decreased. Twenty four days after loxapine introduction and 17 days after the haloperidol, her condition deteriorated rapidly over less than 48 hours. She exhibited immobility, minimal response to stimuli, staring and catalepsy with waxy flexibility. The diagnosis of catatonia was established. Examination revealed tremulous extremities, tachychardia (110 pm) and apyrexia. Creatine phosphokinase levels were 106 UI/l (normal range 0-250). Human immunodeficiency virus, hepatitis, listeria and Lyme serology were negative. Cerebrospinal fluid analysis was normal. Haloperidol was stopped and intravenous clonazepam 5mg/kg was begun. It was not possible to obtain signed consent from the two parents for Electroconvulsive therapy. The patient was transferred to a pediatric intensive care unit. The treatment was standard parenteral nutrition, nursing, intravenous clonazepam 0.05 mg/kg, with regular attendance by a child psychiatrist. Elsa stayed three weeks in this condition. She then began to notice the child psychiatrist, and a few days later she was able to carry out simple requests. Elsa was transferred to an adolescent psychiatric unit. As soon as she could eat by herself again, carbamazepine 400mg per day was begun. Her agitation reduced at a carbamazepine level of 7 mg/l. One month later her condition was stable. However, language difficulties persisted for a further six months. One year after the episode she scored 66 on a repeat IQ test and her RMI was normal. She exhibited no significant residual symptoms except some cognitive impairment. She integrated into a special education facility. These attempts to stop the carbamazepine were followed by depressed mood, aggressiveness and impulsivity; carbamazepine was finally stopped successfully after seven years. Ten years later, Elsa is the mother of two young children and is able to take care of them. She has never had a relapse of her psychotic disorder or catatonic state., Discussion: The etiopathogenic diagnosis is problematic. Some indices in the familial history may suggest a traumatic event. But one to the total residual amnesia it was never confirmed, and traumatic catatonia are extremely rare. Normal CPK levels, with autonomic disturbance limited to tachycardia and the lack of resolution after discontinuance of medication, argues against a diagnosis of neuroleptic malignant syndrome (NMS). But CPK levels are non specific, and NMS without pyrexia has been described. The occurrence of the catatonic syndrome 21 days after the first dose of a neuroleptic could be diagnostic. This case involved a non organic catatonic psychosis followed by neuroleptic induced catatonia. Catatonia is described as a risk factor for the development of NMS and some consider NMS to be a variant of malignant catatonia. The interest of this report is (1) it reinforces the need to be cautious before prescribing neuroleptics in adolescents presenting with symptoms of catatonia; (2) the complete recovery from catatonia after treatment with intensive care and more than three weeks of intravenous clonazepam without the use of ECT and (3) the effectiveness of carbamazepine over a long period of follow-up. Although trials on carbamazepine in catatonia are published, there are no data available for the control of residual symptoms or the long term prognosis, especially in child and adolescent psychiatry., (Copyright (c) 2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Unlabelled: This paper focuses on the questions asked to practitioners regarding compliance to new long-acting atypical antipsychotics (LAAA): how does the comprehensive approach of patients' and carers' attitudes facing treatment challenge it?, Objectives: A review of recent literature shows that LAAA, are still suffering from an "image problem". We aim to describe these negative beliefs and suggest that LAAA indications be reconsidered., Method: Following a comprehensive approach, we interpreted our review on the basis of anthropological criteria. We focused on value-based health and disease models that organize the attitude of patients and carers regarding the depot injection., Results: Multiple negative beliefs attached to the pain, side-effects, and stigmas are well-known to impair adhesion to treatment. Carers understand disease as a lack of insight. Patients experience it as a threat for the Self and a loss of autonomy. The nurse-patient relationship involving injections is an important factor of compliance. When time is devoted by the carer to paying attention to the patient's experience, in order to perceive the patient as a participant, patients are more likely to adopt the injectable route themselves. By doing so, the patient considers the injection as a "protective net" a "lesser evil" by integrating it within his(her) biography., Discussion: A comprehensive approach links the lack of insight to the patient's perception of stigma. Hope for recovery is related by the person him(her)self to his(her) own ability for autonomy. Persons with schizophrenia usually struggle for norms (agonomia). This trend has to be taken into account. LAAA are better indicated when patients are compliant. There is no indication when patients are "pure agonomics" and fight to deny both stigma and medication.

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.

Aripiprazole is indicated for the treatment of schizophrenia in Europe and the United States, and for bipolar disorders in the latter. Nevertheless, a review of recent literature has shown that aripiprazole has been studied in many other disorders, notably resistant depression, anxiety, obsessive-compulsive disorder, borderline personality, Tourette syndrome, addiction, psychotic symptoms in children and adolescents, and neurological and psychiatric disorders in the elderly (late onset delusional disorders, Alzheimer, Parkinson, and delirium). The study of aripiprazole in these numerous indications is motivated by its excellent tolerance and original pharmacological effect (partial agonistic effect on the D2 and 5-HT1A receptors, and antagonistic effect on the 5-HT2A receptors). This paper reviews the recent literature, with particular attention paid to the level of proof provided by these various studies.

Unlabelled: The commercial introduction of atypical antipsychotics (AAP) constitutes a considerable step forward in the sense that it has led to a world-wide reappraisal of the established treatment strategies for people with psychoses (including schizophrenia and affective psychoses). They have allowed refinements in the pharmacologic management of psychoses but they have a higher acquisition cost than conventional neuroleptics. The cost of the newer AAP had a substantial effect on medical resources: the AAP account for only 43.2% of neuroleptic prescriptions, but 76.1% of medical costs associated with neuroleptic drugs, and in terms of treatment costs, a reduction (50%) was found with risperidone compared with olanzapine for a same number of treated patients. The aim of this paper was to examine the use of these drugs, to compare them and to assess their impact within the context of psychiatric hospital practice, by means of analysis of prescribing practices for amisulpride, clozapine, olanzapine and risperidone for all treated patients. We conducted an observational, naturalistic study at Charles Perrens psychiatric Hospital in Bordeaux (France) that reproduced the clinical conditions in which these new drugs are used. Four photographies of all the medical prescriptions concerning atypical antipsychotic drugs were done between October 1999 (four months after the introduction in France of the olanzapine, the last of the new antipsychotics) and June 2001 (n=682 prescriptions). The total amount of these prescriptions corresponded to 527 patients. Treatment groups were compared - first overall and after by considering 2 groups: psychotic and non-psychotic patients - through descriptive analyses of sociodemographic characteristics of patients, diagnosis, percentages of patients receiving concomitant psychotropic medication and/or receiving treatment-emergent side effects and mean dosages of AAP therapy according to concomitant medication. In the same way, we compared the four AAP through their prescribing practices'evolution during the four survey., Results: AAP drugs account for 43.2% of prescriptions (and conventional neuroleptics 56.8% of them). We recorded a significant increase between the four surveys (p<0.02): 36.6% at the beginning to 47.8% at the end of the study. From the 682 collected prescriptions, 72 (10.6%) included clozapine, 130 (19.1%) amisulpride, 229 (33.6%) olanzapine and 251 (36.8%) risperidone. Sixty five percent of AAP prescriptions involved psychotic patients. A relative stability in characteristics of AAP prescriptions during the four surveys was found. So, no significant differences were observed between amisulpride, olanzapine, risperidone, in terms of age, sex, sociodemographic characteristics, unlike clozapine. However, there were statistical differences between all the AAP in the concurrent use of other neuroleptic agents (p<0.02), hypnotic drugs (p<0.006), mood stabilizer drugs (p<0.03), and anticholinergic drugs (p<0.007). Statistically, the mean dosage of amisulpride increased when a mood stabilizer drug was coprescribed (p<0.0007), but it decreased with an antidepressant drug (p<0.004) or an hypnotic drug (p<0.02); clozapine 's one decreased every time an antidepressant drug was coprescribed (p<0.02); with olanzapine, there was a significant increase every time an other neuroleptic agent (p<0.03) or an anticholinergic drug (p<0.006) was associated; then for risperidone, the mean dosage increased with the coprescription of an other neuroleptic agent (p<0.00002), an anticholinergic (p<0.00003) or an adrenolytic drug (p<0.04). The pattern of prescribing practices that emerges from our four surveys suggests that these new AAP are significantly more and more often associated with a stabilizer mood drug (p<0.009) (particularly the olanzapine) or/and an anxiolytic drug (p<0.05) (like the amisulpride in particular). Considering the four AAP globally, but more with the risperidone, the association with a neurovegetative corrector agent decreased (p<0.004) during the four surveys. Then, concerning the psychoticng the four surveys. Then, concerning the psychotic patients, the AAP were significantly more often associated with other neuroleptic agents (p<0.03), the amisulpride in particular, with anticholinergic drugs (p<0.00005), but significantly less with mood stabilizer drugs (p<0.00003) principally the amisulpride and the risperidone, with antidepressant drugs (p<0.02) particularly the risperidone. This kind of survey, however it is too much rare, is very important because it shows the clinical conditions in which these new drugs are really used. The results show that AAP appear to be the replacements of the older neuroleptics used in the treatment of psychoses, including particularly schizophrenia, but also in the treatment of mood disorders, and they reflect actual clinical practices. Other surveys must be achieved to see if our study confirms the general trend concerning the use of these drugs and so as to reassess these prescribing practices.

Weight gain associated with neuroleptics or antipsychotic treatment is well known by psychiatrists, but is too rarely considered as justifying a specific treatment program. Overweight is a risk factor for somatic disorders and can have a negative influence on self-esteem and self-confidence. This can lead to poor observance, and relapse of psychotic symptoms. Some studies try to describe the weight fluctuations according to the different neuroleptics and taking into account other variables like treatment duration, age or sex. Mechanisms of weight gain are less studied, in spite of evidence that neuroleptics interact with receptors of dopamine, norepinephrine, serotonin, histamine and acetylcholin, all implicated in a way or another, in weight regulation. Antipsychotics, like clozapine and olanzapine, are more concerned with neuroendocrine and neurovegetative interactions, and are responsible for the most severe weight increases. Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain. The paper discusses the clinical and the epidemiological data, and indicates the methodological problems for such studies. Some hypotheses about the pathophysiological aspects of this side effect are made, in regard to growing knowledge about the biological mechanisms of weight regulation. Some solutions for a better consideration and caretaking of patients with such problems or "at risk" treatment are proposed.

Antipsychotic drugs are widely used in the long term treatment of bipolar and schizoaffective disorders. Nevertheless clinical trials devoted to the specific assessment of the mood stabilizing effect of these drugs are quite rare. Among recent studies only those by S. McElroy on olanzapine and by R. Bowden on divalproex have included mood symptoms as inclusion and outcome criteria. This paper reviews the different methodological proposals both in term of protocol designs (retrospective, naturalistic, longitudinal and prospective studies) and of efficacy criteria (time to relapse, reasons for drop outs, treatment switch, functional status).

Among elderly disruptive behavior agitation and aggressiveness are frequent and often related to dementia. They are known for increasing the risk of patients' institutionalization and causing distress to families and care givers. When a drug prescription is required, physicians have to take into account the high sensitivity of elderly. Tiapride is an atypical neuroleptic which acts preferentially on D2 and D3 dopaminergic receptors. Several papers concerning results of clinical trials conducted in Europe and Japan have been published and reviewed in this article. The interest of tiapride in the treatment of elderly agitation and aggressiveness has been assessed in four double blind clinical trials including more than 700 patients. The efficacy of tiapride (aggressiveness, agitation, delusion and wandering) was demonstrated in a trial versus placebo (p = 0.027) including 324 patients treated for 28 days with 75 to 150 mg/d. Furthermore the superiority of tiapride (175 to 450 mg/d) on chlorpromazine (18 to 112.5 mg/d) was shown in two trials where 262 patients were treated for four weeks, and a recent survey highlighted that tiapride (400 mg/d) is as efficient as melperone (100 mg/d), the only neuroleptic to be indicated in treatment of elderly agitation and aggressiveness in Germany. Besides, 30 open clinical trials including around 1,000 patients have been conducted and have shown homogeneous and positive results. In the two trials versus chlorpromazine, the safety of tiapride was better, with especially less drowsiness, extrapyramidal symptoms, and dry mouth. Compared to lorazepam, in healthy subjects, tiapride caused less memory impairment. European and Japanese open studies confirmed the safety of tiapride in the elderly. In conclusion, tiapride at doses of 100 to 300 mg/d, appeared to be a therapy of elderly agitation and aggressiveness, at less as efficient as the other drugs used in this indication. Furthermore, the safety of tiapride is an advantage compared to benzodiazepines and neuroleptics.

This study reports a clinical experience among twenty schizophrenic patients treated by clozapine during two years and eight months within a range extending from three months to seven years. These twenty patients had previously shown long-term resistance to usual neuroleptics but three out of them met the diagnosis of mental retardation or childhood disintegrative disorder (F.84.3-ICD 10). These patients were put under clozapine for their violent behavior. The methodology was retrospective, descriptive with intra-individual comparison, each patient being his own reference before and after treatment. Diagnosis met CD 10 criteria and were assessed without using standard examination. This study aimed at assessing once more clozapine efficacy and tolerance upon a long time follow up. Single therapy has been the rule and dosages have been progressively increased reaching a mean daily dosage of 350 mg per day. The efficacy, assessed by the way of BPRS, GAF (DSM III-R) and simplified form of CGIS, has been verified in approximately 30% of the patients, mainly concerning positive symptoms. Clozapine was also able to alleviate severe behavior troubles brought about by delusional states, without this latter being markedly softened when it was a long term one. Clozapine tolerance has shown it to be satisfactory, however we noticed the occurrence of a leucopenia with neutropenia after seventeen weeks of treatment, followed, some days later, by a Quincke oedema, which forced to interrupt the treatment. White blood cells came back in a normal range fifteen days later. The other side effects (transitory hypersialorrhea, tachycardia, without clinical and ECG perturbations) have been usually well tolerated and have never caused treatment interruption. No extrapyramidal side effect have been noticed among our twenty patients. The end of this paper consists in the presentation of four clinical cases: one about the efficacy of clozapine upon violent antisocial behaviour in a schizotypital disorder; one delusional chronic schizophrenic patient whose violence has been controlled despite of the delusion; one paranoid schizophrenic patient who has been able to maintain a satisfactory professional and family adaptation; and finally a childhood disintegrative disorder (F.84.3-ICD 10) in whom occurred the only leucopenia side effect of our study. These four clinical cases have seemed particularly meaningful regarding our clinical experience of clozapine which has been lasting for almost seven years now.

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

Various pharmacologic agents have been reported to be effective in treating negative symptoms of schizophrenia. European schools of psychiatry and especially the French one assumed the opinion that part of negative symptoms of schizophrenia do respond to neuroleptics. In light of effects of reserpine and some phenothiazines on negative schizophrenia, various pharmacologic agents have been studied focusing on these properties. Various papers devoted to this question concluded that some drugs, particularly neuroleptics, can be considered as disinhibitors: phenothiazines (thiotixene, trifluoperazine, fluphenazine, pipotiazine), butyrophenones (trifluperidol, risperidone), diphenylbutylpiperidines (pimozide) and benzamides (sulpiride, amisulpiride). Major part of controlled studies concluded to the better efficacy of low doses of such drugs on negative symptoms, while high doses are almost inefficient. Some studies concluded in the activity of clozapine on negative symptoms of schizophrenic patients. To answer the question whether negative symptoms of schizophrenia are improved concomitantly or independently of improvement in positive symptoms or of decrease in extrapyramidal side effects and/or depressive symptoms, the authors prospectively followed up for 30 months, 13 DSM-IV resistant schizophrenics. Symptoms were assessed by means of 18 item Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Extrapyramidal Symptom Rating Scale (ESRS). Improvement in negative symptoms was significantly correlated to improvement in positive ones and to scores in ESRS. Many open studies concerning anti-depressants and other drugs have been published; however controlled studies are necessary to confirm these data.

This paper summarizes the presentations made during the Lucca symposium (1-3 October, 1977) on long-acting neuroleptics. The authors tried to present advantages and inconveniences of this therapeutic compared to the "classical" neuroleptic therapeutics: - in patients with an acute symptomatology; - in stabilized patients. The main advantage is that one can be ensured that the drug has been or not been taken.