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Haloperidol is frequently used as first-line treatment for delirium. The Swiss Smarter medicine campaign recommends to favor non-pharmacological interventions and treatment of the underlying causes, in order to limit the use of haloperidol. When antipsychotics are necessary, they should be prescribed cautiously, taking into account contraindications and potential side effects. This article emphasizes the importance of history taking in patient with delirium before prescribing haloperidol., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Malignant catatonia is a life-threatening syndrome, associated mostly with psychiatric diseases but also with neurological and neurodegenerative syndromes. We report the case of a 72-year-old patient, hospitalized for a major depressive episode with delusional symptoms, who presented a malignant catatonia. The patient had been transferred to an intensive care unit and treated with electroconvulsive therapy (ECT) leading to a rapid disappearance of the catatonic syndrome associated with a remission of the depressive symptoms. Complementary investigations helped us to secondarily diagnose a Lewy Body Dementia, which probably caused, associated with a treatment by haloperidol, the onset of catatonia. This case illustrates the need of an early diagnosis of neurodegenerative diseases in psychiatric outpatients and the importance of a quick management of catatonia, including ECT., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Sydenham's chorea is the most common acquired cause of chorea in the third world. We report a case of recurrent chorea successfully treated with sodium valproate. Miss A.C, aged 16, with a history of recurrent angina reported an episode of choreic movements 2 years before requiring treatment with haloperidol and prevention of rheumatic fever. The patient interrupted her treatment with occurrence of a relapse a few months later. Brain MRI and transthoracic ultrasound were normal. Preventive treatment with extencilline and haloperidol was restarted without any improvement, hence the treatment with sodium valproate. The patient responded very well after 2 months of treatment, without recurrence at 3 years' follow-up. The treatment of Sydenham's chorea was based on neuroleptics. Recent studies advocate the use of other more effective and better tolerated molecules.

Introduction: Priapism is a persistent, and often painful, penile erection, lasting more than 3 hours, not usually associated with sexual stimuli. It is a urological emergency that can cause serious complications. Drugs are responsible of the onset of 25 to 40% of cases of priapism. Several classes of medication are involved: antidepressants, antihypertensives, anticoagulants, alpha-blockers and some psychoactive substances (alcohol, cocaine, cannabis...). However, about 50% of drug related priapism is due to antipsychotics (AP). Clinicians should be aware of this rare side effect because of the severity of its complications and the difficulty of its management, especially in non-stabilized psychotic patients., Case Report: We report a case of a 22-year-old male Moroccan patient, diagnosed with schizophrenia, who had been admitted for the first time to a psychiatric hospital for management of a psychotic episode. First, he received 15 mg per day of haloperidol, and seven days later he developed priapism. The patient was immediately referred for urological care. Aspiration and irrigation of the corpora cavernosa was proposed, but could not be performed because of patient refusal, and the erection resolved spontaneously after 10 hours. Haloperidol was stopped, and four days later the patient was switched to 10mg per day of olanzapine. After 10 days of treatment, he developed a second episode of priapism, and olanzapine was also stopped. A cavernosal aspiration-irrigation was performed in emergency; which resulted in the partial detumescence of the penis. Two days later, and despite therapeutic abstention, the patient presented another episode of priapism. The indication of a revascularization of the corpora cavernosa was proposed, but again the patient refused the surgery. Finally, the patient was administered 400mg/day of amisulpride, with a favorable outcome. Priapism disappeared after a month with the installation of fibrosis and partial loss of erectile function., Discussion: The precise mechanisms of the role of AP in the occurrence of priapism are not all known and a multifactor etiology seems the most likely. Neuromuscular hypothesis is the most mentioned, involving the blocking action of alpha1-adrenergic receptors of the corpora cavernosa for which most of AP have an affinity. The occurrence of priapism in a psychotic patient, especially during periods of decompensation, raises a number of challenges for the medical staff. First, the non-recognition by the patient of this side effect, and its potentially severe consequences. Second, the absence of link between dose and duration of AP treatment on one side, and the onset of priapism on the other, which makes it hard to predict. The third challenge is the choice and initiation of another AP. The literature reveals many cases of priapism in both conventional and atypical AP, the presence of a predisposition to this type of incident has been reported. However, few authors have focused on alternatives to provide for these patients. Amisulpride is currently the only molecule that does not have alpha-adrenergic affinity and is therefore preferred in these cases., Conclusion: Priapism is a rare but serious adverse event of AP medication. Informing patient about the risk of priapism would help to report it early and prevent erectile dysfunction. Switching to another AP with less alpha1-blocking properties is generally recommended., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Acute ethanol intoxication is frequent in emergency departments. The clinical presentation is highly variable and ranges from an inebriety to a coma and sometimes an agitated patient. You have to examine completely the patient and to do complementary exams with a capillary glycemia as the minimal standard. We must keep in mind that an acute ethanol intoxication is a diagnosis of exclusion. With trauma patients, we have to keep a low threshold for asking radiological advanced imaging, like cerebro-cervical CT scan. The patient should be reexamined frequently. The treatment is a supportive one. If the patient is agitated, you can give him haloperidol or a benzodiazepine. Before discharge, the patient should see the alcohologic team.

Introduction: The term tardive dyskinesia (TD) is used to describe abnormal movement, primarily associated with typical antipsychotic drugs, which are used to treat psychotic states such as schizophrenia. TD is characterised by repetitive involuntary purposeless muscle contractions that force parts of the body into abnormal, and sometimes painful, movements or postures. These movements are involuntary and are difficult or impossible to control. TD usually begins with the face, mouth, lips and tongue, and includes grimacing, lip-smacking, tongue movements and rapid blinking. It may also involve the rest of the body and produce involuntary gestures, tics and writhing movements. TD is severe physically and socially disabling. Schizophrenia is thought to be the psychiatric diagnosis the most frequently associated with TD., Materials and Methods: The purpose of this article is to study the characteristics of TD in a Tunisian sample of 157 schizophrenics. A variety of demographic and clinical information was obtained by a questionnaire. Diagnoses of schizophrenia and TD were determined by using DSM-VI-R criteria. TD was assessed using the Abnormal Involuntary Movements Scale (AIMS)., Results: The average age in this sample was 37 ± 6 years. The intermediate duration of evolution of the disease was 8 ± 3 years with a medium full number of hospitalizations of 4 ± 3. We found 58% of the paranoid sub-type. The intermediate duration of exposure to classical neuroleptics was 7 ± 3 years. The average of daily neuroleptic amount was 572.9 ± 145.3 equivalent milligrams of chlorpromazine. Extended release antipsychotics were used in 64.3% of cases, with fluphenazine deaconate in 90% and haloperidol deaconate in 10%. Anticholinergics were used by 74.5% of patients, with use of biperidene in 96% of cases. Therapeutic observance was good in 89.2% of patients. The prevalence of TD was an estimated 35%. The average of AIMS score was 17 ± 9, with a minimal score of 3 and a maximal one of 34. The distribution of patients according to severity found a prevalence of 52.7% of subjects with moderate TD, 38.2% with light TD and 9.1% with severe TD. The distribution of patients according to type, according to DSM-IV criteria, found 78.4% of cases with choreiform TD, 17.5% of cases with athetosic TD and 4.1% of cases with rhythmic TD. The intermediate duration of evolution of TD was estimated at 18 ± 6 months with a minimal duration of 3 months and a maximum of 72 months. The distribution of subjects according to duration of evolution of TD found that approximately three quarter of patients presented with TD that had evolved since one duration, lower or equal to one year. The average age of patients at the moment of installation of TD was estimated at 36 ± 6 years with 22 years as a minimal and 46 years as a maximal age. Among them, 81.8% of patients were aged over 30 at the time of the installation of TD., Conclusion: The majority of patients with schizophrenia in Tunisia are still treated with typical antipsychotic drugs, and that's why the prevalence of TD remains relatively high., (Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Acute psychotic access is defined as the occurrence of a single, acute, and intense psychotic episode in a subject without a neurological or psychiatric history. Isoniazid (INH), a major antibacillar, is the drug most often involved in the occurrence of this psychiatric disorder. However, this side effect is rare and only a few cases have been reported in the literature., Case Report: A 57-year-old female patient with diabetes mellitus presented miliary tuberculosis for which an antibacillar treatment was prescribed. Three days later, she presented an acute psychotic access requiring the withdrawal of the INH and the prescription of neuroleptic drugs, without any pyridoxine supplementation. The lab tests were normal. The good clinical evolution after the INH withdrawal confirmed its imputabilty., Conclusion: Acute psychotic access is a severe and exceptional complication following the administration of INH. Emergency treatment is the only guarantee of a good outcome., (Copyright © 2010 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.)

When fever occurs in a patient treated with a neuroleptic, the diagnosis of a neuroleptic malignant syndrome is difficult to differentiate to that of an infectious event. Among inflammation biomarkers of inflammation, serum procalcitonin levels increase both quickly and specifically during a bacterial infection. We report the first case of a neuroleptic malignant syndrome associated with a significant increase of serum procalcitonin levels, without concomitant septic syndrome. The neuroleptic malignant syndrome might be a non-infectious clinical situation associated with an increased serum procalcitonin concentration.

Objectives: To appreciate the impact of the neuroleptic treatment on the neurological soft signs (NSS) in schizophrenic patients and to examine their relation with the treatment response based on the level of CGI-improvement., Methods: A cross-sectional study bearing on 66 schizophrenic patients: untreated patients (N = 13) and treated patients (N = 53). All patients were assessed by the Krebs et al. Neurological Soft Signs Scale and the Clinical Global Impressions (CGI)., Results: No difference has been noted concerning the NSS total score between treated and untreated schizophrenic patients. Concerning the NSS sub-scores, we have noted a significantly difference in the sensory integration sub-score. In treated patients, no correlation was found between NSS and daily dosage or duration of exposure of neuroleptic treatment, extrapyramidal symptoms and level of CGI-improvement., Conclusion: The excess of NSS in schizophrenic patients is independent of the neuroleptic treatment, suggesting that NSS represent a neurodevelopmental risk factor for schizophrenia.

Unlabelled: Schizophrenia is a disease affecting the young adults and amounts to approximately 300,000 people in France. The French public psychiatric sector takes care of approximately 150,000 adults schizophrenics: 50% benefit from ambulatory care, 50% are in partial or full-time hospitalization care. Schizophrenia represents the first diagnosis that psychiatric sectors take in charge. The costs associated with schizophrenia, mainly hospital costs, are important and were estimated at 2% of the total medical costs in France. In the French social welfare system, the social costs (pensions, allowances, managements of custody or guardianship by social workers) are also to be taken into account: it amounts to a third of the global direct cost. Schizophrenia also generates indirect costs (losses of productivity and premature deaths) which would be at least equal, or even more important, than direct medical costs. The non-compliance to the antipsychotic treatment is a major problem with people suffering from schizophrenia. Indeed the lack of compliance to the treatment, estimated at 20 to 40%, is a major handicap for schizophrenic patient stabilization. The poor level of compliance is due to many various causes: adverse effects that are considered unbearable, medicine viewed as persecutory, negation of the disease, nostalgia for the productive phases of the disease, lack of social support, complexity of the prescription, relapse itself. Compliance is thus influenced by the patient's clinical features, local provision of health care and the specific nature of the drug (adverse effects, pharmaceutical formulation). The atypical antipsychotics present fewer extrapyramidal side effects and reduce the cognitive deficits associated with the disease, which results in improved compliance. Long-acting injectable antipsychotics allow a better therapeutic compliance and thus better efficacy of the treatment. Several studies have shown a significant improvement in compliance related to the pharmaceutical formulation of antipsychotics. Hospitalization and relapse risks are lower in compliant than in non-compliant patients., Objectives: The main objective of this pharmacoeconomic analysis is to evaluate the impact in terms of medical benefits and costs of the following strategies: 1. Risperidone long-acting injection: first long-acting injectable atypical antipsychotic; 2. Haloperidol depot: long-acting injectable conventional neuroleptic; 3. Olanzapine: atypical antipsychotic available commercially in oral formulation., Methods: The target population defined for the study are young schizophrenic patients treated for at least 1 year and whose disorder has not been diagnosed for longer than 5 years. The time horizon is 2 years. A cost-effectiveness analysis is performed. The perspective adopted is the French Health System. The main hypothesis of the model is that an increase in compliance linked to the use of long-acting injectable formulation could lead to an increased efficacy and a modification of the cost-effectiveness ratio. A decision tree was built. Six periods of follow-up are identified with a duration of 4-months per period. The tree contains 3 principal arms, each one corresponding to a specific treatment: risperidone LA injection, haloperidol decanoate and olanzapine. For each arm, at the chance node, two health states are identified: either the patient responds favourably to the treatment or does not respond favourably and requires a switch to another drug treatment. After a period of response, the patient can either remain in the same state or experiences a clinical deterioration. If the patient presents a clinical deterioration, he can either go back to a positive response state after a period of intensive follow-up or remain in an insufficient response state; in this case, a change of antipsychotic treatment is necessary. In the model, a patient should receive four different treatments before a long-term hospitalization takes put in place. According to the market authorization labelling, clozapine is proposed only as a 2nd or 3rd line therapeutic option, so when at least one or two successive neuroleptics have failed. The efficacy data used in the model are provided by clinical research recently published. These studies estimate the efficacy of oral risperidone, LA risperidone, olanzapine, and treatment by haloperidol. When available data in the literature were insufficient, the opinion of experts was sought. The effectiveness criteria is the rate of patients treated successfully: patients responding to the initial treatment with the possibility of experiencing one or two episodes of clinical deterioration but without requiring a switch to another drug during 2 years of follow-up. The base case is as follows: efficacy for oral risperidone is used for the LA risperidone strategy, increased by 10% within the first 4 months of follow-up; efficacy for oral haloperidol is used for haloperidol depot, increased by 5% within the first 4 months of follow-up; for olanzapine, observed data in clinical trials were applied. The hypotheses for long acting forms are rather conservative because the increase of efficacy which can be expected for the long-acting injectable formulations varies between 5% to more than 30% according to the literature data. The analysis of sensibility includes three scenarios: scenario 1: for LA risperidone, 5% of patients treated successfully improvement in regard to oral risperidone instead of 10% in the base case; scenario 2: for haloperidol depot, 10% of patients treated successfully improvement in regard of oral haloperidol instead of 5% in the base case; scenario 3: the results of an open trial conducted within the framework of the LA risperidone license are used, leading to an increase of up to 13,3% of the rate of successfully treated patients, compared to oral risperidone literature data. As for the side effects, only extrapyramidal symptoms were considered. Other side effects are described in the literature such as the obesity or the occurrence of a diabetes; these effects were not taken into account in the model, their impact on the cove-rage of schizophrenic patients and on resources utilisation being poorly known. Only direct medical costs were considered in the pharmaco-economic analysis. Two types of costs were identified: hospital costs and community care costs. The stays in overnight hospitalisation and day hospitalisation were derived from the Disease Related Groups (DRG) and valued from the data of the National Cost Study (Etude Nationale de Coûts; 1999). The DRGs corresponding to the diagnosis of schizophrenia are the DRG 627 (complete hospitalization) and DRG 819 (day hospitalisation). Ambulatory care: procedures and visits, were valued in euros in reference with the tariffs for reimbursement issued in the Naming General of the Professional Acts (NGAP) and published by the French National Health Insurance (Year 2001). Medication consumption was quantified by using the daily dosage specified in the the MAA and the French prescription database IMS-Dorema. The cost of medicines was valued from tariffs 2001 (SEMPEX). LA risperidone price being not fixed to date, the reserved hypothesis is a 141,62 Euro retail price. As schizophrenia is listed among the diseases reimbursed at a 100% rate by the Health insurance, out of pocket expenses by patient are not considered in the analysis. The cost for the extrapyramidal effects was attributed to all the strategies. This cost was calculated according to the rates of extrapyramidal effects occurrence collected in the literature. Globally, in the published studies, the incidence of the side effects for the patients treated by olanzapine or risperidone is similar. It was thus decided by the experts to use the same rate of occurrence for extrapyramidal effects for olanzapine and risperidone (20%). This rate is 40% for haloperidol decanoate, 10% for oral clozapine. For the cost estimation, the expenses for treating a schizophrenic patient for two years were taken into account., Results: The results show that in two years, LA risperidone is more effective than the two other antipsychotics. After 2 years, the rate of patients treated successfully is 82,7% for LA risperidone, 74,8% for olanzapine and 57,3% for haloperidol depot. The 2 year-cost per patient treated by LA risperidone is 14,055 Euro. This cost is 14,351 Euro and 17,203 Euro respectively for the strategies olanzapine and haloperidol depot. The cost-efficacy ratios per patient successfully treated are 16,995 Euro for the strategy LA risperidone, 19,186 Euro for olanzapine and 30,023 Euro for haloperidol depot. LA risperidone is a dominant strategy compared with both olanzapine and haloperidol depot. Scenario 1 shows that LA risperidone strategy remains the most effective. Indeed, this strategy allows a response increase of 3,5% regarding olanzapine strategy and of 21% regarding haloperidol depot strategy. Under the hypothesis tested in scenario 1, LA risperidone is a partial dominant strategy against olanzapine and a total dominant strategy against haloperidol depot. In scenario 2, as efficacy is improved for haloperidol decanoate (61,10%), a decrease of 1,763 Euro in the cost per patient treated is observed for this strategy. Cost per patient treated successfully and efficacy for LA risperidone and olanzapine are the same than in the base case. LA risperidone is a total dominant strategy against olanzapine and haloperidol decanoate. In scenario 3, the rate of patients treated successfully at 2 years is 88,6% for LA risperidone with a cost per patient of 12,347 Euro. LA risperidone is dominant against olanzapine and haloperidol depot., Discussion and Conclusion: The schizophrenia is a relatively frequent disease. (ABSTRACT TRUNCATED)

We report on the case of a 20 year old woman with no previous psychiatric history, who displayed a first episode of catatonia with acute onset. Symptoms started plainly with sudden general impairment, intense asthenia, headache, abdominal pain and confusion. After 48 hours, the patient was first admitted to an emergency unit and transferred to an internal medicine ward afterwards. She kept confused. Her behaviour was bizarre with permanent swinging of pelvis, mannerism, answers off the point and increasingly poor. The general clinical examination was normal, except for the presence of a regular tachycardia (120 bpm). The paraclinical investigations also showed normal: biology, EEG, CT Scan, lumbar puncture. Confusion persisted. The patient remained stuporous, with fixed gazing and listening-like attitudes. She managed to eat and move with the help of nurses but remained bedridden. The neurological examination showed hypokinaesia, extended hypotonia, sweating, urinary incontinence, bilateral sharp reflexes with no Babinski's sign and an inexhaustible nasoorbicular reflex. The patient was mute and contrary, actively closed her eyes, but responded occasionally to simple instructions. For short moments, she suddenly engaged in inappropriate behaviors (wandering around) while connecting back to her environment answering the telephone and talking to her parents. The patient's temperature rose twice in the first days but with no specific etiology found. During the first 8 days of hospitalization, an antipsychotic treatment was administered: haloperidol 10 mg per os daily and cyamemazine 37.5 mg i.m. daily. Despite these medications, the patient worsened and was transferred to our psychiatric unit in order to manage this catatonic picture with rapid onset for which no organic etiology was found. On admission, the patient was stuporous, immobile, unresponsive to any instruction, with catalepsy, maintenance of postures, severe negativism and refusal to eat. A first treatment by benzodiazepine (clorazepate 20 mg i.v.) did not lead to any improvement. The organic investigations were completed with cerebral MRI and the ruling out of a Wilson's disease. Convulsive therapy was then decided. It proved dramatically effective from the first attempt; 4 shocks were carried out before the patient's relatives ask for her discharge from hospital. The patient revealed she had experienced low delirium during her catatonic state. The clinical picture that followed showed retardation with anxiety. She was scared with fear both for the other patients and the nursing team. She kept distant and expressed few affects. The treatment at the time of discharge was olanzapine 10 mg per os. She was discharged with a diagnosis of catatonia but with no specific psychiatric etiological diagnosis associated. She discontinued her follow-up a few weeks later. After one year, we had no information about her. Catatonia has now become rare but remains a problem for clinicians. We reviewed data concerning short term vital prognosis and psychiatric long term prognosis in catatonia. Lethal catatonia is associated with acute onset, both marked psychomotor and neurovegetative symptoms. In the light of literature, there is no proband clinical criterion during the episode that is of relevant diagnostic value to ascertain the psychiatric etiology.

Olanzapine (Zyprexa), a neuroleptic, has obtained marketing authorization for treatment of schizophrenia. The clinical file is satisfactory, but in the absence of relevant trials, it has not yet been demonstrated that olanzapine has a specific activity on the positive or negative symptoms of schizophrenia. The global efficacy of olanzapine was not substantially different from that of haloperidol in two of the three comparative trials published to date. The only relevant comparative trial fails to demonstrate the superiority of olanzapine over risperidone. Olanzapine has fewer adverse neurologic effects than haloperidol, but there is no evidence that it differs from other recent neuroleptics in this respect. Olanzapine can have anticholinergic adverse effects and frequently causes weight gain. Active surveillance is required because subclinical cases of elevated transaminase levels, increased blood pressure, and QT prolongation were observed in clinical trials (2500 patients treated).

Background: Sydenham's chorea was the most common form of acquired chorea in childhood. Its incidence has declined since the use of antibiotics. The aim of our study was to determine the hospital incidence of this disease and to illustrate the clinical characteristics and outcome of this disease in Tunisia., Population: Retrospective study of 15 cases of Sydenham's chorea, seen between 1987 and 1997., Results: Our patients (five boys and ten girls) represented 5.6 per 1000 hospitalized children. Their mean age was 10.5 years. Two patients had a history of rheumatic fever and five had a history of throat infection during the month before chorea. The onset of symptoms was acute in five cases and insidious in ten. Choreic movements were generalized but asymmetrical in 12 cases, and unilateral in three. Psychological disorders were noted in nine cases and hypotonia in six. Rheumatic carditis was found in three patients. No patient had an obvious increase in sedimentation rate, and antistreptolysin were increased in 50% of cases. All patients were given haloperidol and five steroids, 11 were given antibiotics at the attack of chorea and 13 received secondary prevention with benzathine penicillin. Initially, abnormal movements disappeared in all cases after a mean of three months. Three patients relapsed and two among them still show abnormal movements and psychological disorders after a follow-up of 3 and 3.5 years respectively., Conclusion: Sydenham's chorea, although less frequent than previously, is not exceptional in Tunisia. Malignant forms are not observed, but two of 15 patients developed a chronic form with sequelae. No correlation is found between outcome and secondary prevention of streptococcal infections.

Purpose: The purpose of this study is to provide an economic comparison of olanzapine-treated and haloperidol-treated patients from the subset of French patients who participated in a large, international, randomised clinical trial in schizophrenia., Methods: Patients were evaluated from randomisation until discontinuation, drop out or completion of the 52-week study. The primary clinical measure was "clinically important response" (derived from BPRS total scores). The secondary measure was "clinically important improvement" (derived from CGI severity of illness scores). The primary economic measure was mean per diem, per patient total direct medical costs., Results: A total of 275 French patients where included in the study. Demographics and other baseline differences between olanzapine- and haloperidol-treated patients were not statistically significant. Olanzapine-treated patients (205 +/- 142 days) experienced significantly (p < 0.001) longer evaluation periods than haloperidol-treated patients (132 +/- 129 days). Olanzapine-treated patients (54%) were significantly (p = 0.03) more likely to experience a clinically important response than haloperidol-treated patients (40%). Olanzapine-treated patients (69%) were significantly (p = 0.02) more likely to experience clinically important improvement than haloperidol-treated patients (54%). The mean per diem, per patient total direct medical cost was statistically lower (p = 0.033) for olanzapine-treated patients (FF619 +/- 509) compared to haloperidol-treated patients (FF756 +/- 478)., Conclusion: Olanzapine treatment was associated with significantly better clinical outcomes and per diem total direct medical cost than haloperidol treatment. The findings indicate that olanzapine is dominant compared to haloperidol for the treatment of schizophrenia, in the context of analysed data. These findings produce increased relevance in France to the existing evidence supporting olanzapine's cost and effectiveness profiles.

This is the presentation of an adolescent's clinical case who tried to commit suicide with a fire arm during a depressive crisis. An emphasis is placed on the family interaction model and on a more global approach of the patient's personality. The authors underlined some of the problems raised by the diagnostic approach linked to the delirious syndrome, full of psychotic elements: themes of persecution, mystico-religious themes associated with impulsive escapade, all of them going with a depressive state. They gave also an important place to a pluridisciplanary treatment in those particular stages of crisis.

Haloperidol was synthesized on the 11th of February 1958 by Bert Hermans at the Janssen Laboratories, Beerse, Belgium. Simple but ingenuous methods of animal pharmacology suggested to Paul Janssen and his collegues that this butyrophenone derivative, called R1625, then halop-peridol, would be of great interest: qualitatively, the pharmacological action of R1625 was similar to chlorpromazine, but R1625 was very more powerful since it produced effects with much smaller doses than chlorpromazine. Soon after the synthesis and animal studies, haloperidol was administered in humans by Divry, Bobon et Collard, psychiatrists at the Liege Hospital. The first clinical publication, on the 28th of October, 1958, described the effects of haloperidol in agitation states. The subsequent clinical studies, including those of the prestigious French school of Sainte-Anne hospital, confirmed that haloperidol belongs to the pharmacological family of neuroleptics, as it was defined by J. Delay and P. Deniker in 1955. These clinical studies demonstrated also that haloperidol was particularly active against delusions and hallucinations. Numbers of chronically inpatients were able to leave hospital and to live home thanks to this new drug, which remains one of the more prescribed neuroleptics 40 years after its discovery.

Results of recent studies in pharmacotherapy in autism are presented. Haloperidol, fenfluramine and naltrexone have been the most extensively studied drugs in systematic research. Haloperidol appeared to decrease levels of hyperactivity, stereotypies, emotional lability but also abnormal object relations and social withdrawal. However, the therapeutic effect was generally modest and long term administration was associated with dyskinesias in autistic children. The frequent hyperserotonemia in autism has suggested the use of fenfluramine, an antiserotoninergic agent. Although the initial reports were optimistic, more recent carefully designed studies often failed to show that fenfluramine was superior to placebo. Naltrexone, a potent opiate antagonist, was explored following the opioid hypothesis based on the similarity between autistic symptomatology and abnormal behaviors observed in opiate addicts and in laboratory animals administered opiates and on the abnormalities of endogenous opioids that exit in a subgroup of autistic children. However, the current studies do not concur and no definite conclusions can be made of the efficacy of naltrexone at present time. Low doses of amisulpride which have been shown to improve negative symptoms in schizophrenia and serotoninergic antidepressants, which have proven effective in repetitive and ritualized behaviors, have recently began to be evaluated in controlled studies. At present time, no medication has shown to alter the course or the symptoms of autism, but some seem to be effective in reducing severe aberrant behaviors.

The study concerned 7 patients suffering from schizophrenic disorder according to the DSM III R criteria, treated with a stable dose of haloperidol decanoate (Haldol décanoas) added with fluoxetine (Prozac) from 20 mg to 40 mg/day because of major depression. Patients were assessed at baseline and weekly during the first cycle, and then once a month before each haloperidol decanoate injection, using the brief psychiatric rating scale (BPRS), the general clinical impression scale (CGI) and the Montgomery and Asberg depression rating scale (MADRS). Extrapyramidal and anticholinergic side-effects, blood pressure and pulse were noted. Determinations of plasma and red blood cells concentrations of haloperidol and reduced haloperidol, and of fluoxetine and norfluoxetine, were conducted at the same time than clinical evaluations. For all patients, we observed an improvement by the end of the first week, which became significant at the end of the second week, and continued in subsequent weeks (more than 30 per cent). Two weeks after the addition of fluoxetine, a very significant increase in haloperidol concentrations (more than 100 per cent) was noted; fluoxetine seems to have pharmacokinetic interactions with haloperidol, either by inhibiting its hepatic metabolism (inhibition of cytochrome P450 isoenzyme) or/and by displacing it from protein binding sites.

Haloperidol (HAL) is a widely used and clinically effective neuroleptic. Its metabolism differs in various animal species. In humans, reduced haloperidol (RHAL), a hydroxy metabolite of HAL, is produced by a cytosolic ketone reductase. Interconversion is known to occur whereby HAL is found in the plasma after administration of RHAL in vivo. Interconversion of HAL and RHAL has been observed in man. However, the capacity for reductive HAL is greater than its oxidation back from RHAL. RHAL, the resulting metabolite of HAL, is reported to be about 10-25% as active as HAL in an animal model. Large intersubject variation has been observed in the pharmacokinetics of HAL and RHAL. A wide variation in reductive drug-metabolizing has been observed in schizophrenic patients treated with HAL. Both high and low RHAL/HAL ratios or RHAL levels were reported to be linked to poor response in HAL-treated patients and might be correlated with the therapeutic window effect of HAL treatment. It is conceivable, therefore, that subjects with high reductive capacity relative to oxidative capacity may have less therapeutic response from the same dose of HAL than those with a low reductive capacity relative to oxidative capacity. This aim of this study was to investigate the HAL reduction among a sample of HAL-treated schizophrenic patients. Because ketone reductases are generally not tissue specific, we investigate the reductase activity in Red blood cells (as described by Inaba), before and during the treatment. Steady-state plasma drug levels during 2 weeks of treatment were quantified. We examined the relationships between fixed doses of HAL treatment, Red blood cells ketone reductase activity, plasma HAL and RHAL levels and the percentage of change of the Positive and Negative Syndrome Scale for Schizophrenia. The participants in this study were 15 inpatients consecutively being treated in the adult psychiatric wards of the University of Lille. All subjects met DSM III-R criteria for schizophrenia (paranoid form). Upon induction subjects were evaluated clinically by trained raters using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Subjects were required to score 40 or higher on the general psychopathology subscale of the PANSS to continue participation. All subjects were drug free. Haloperidol was administered orally at three times daily dose. Patients were randomized to treatment at three orally fixed doses: 6 mg per day, 10 mg per day and 15 mg per day. Patients were treated for 2 periods of one week. At the end of each period, dosages could be modified according to the clinic evolution of the patient. PANSS was repeated by the same raters blinded to the haloperidol dosage, plasma concentration and Rbc haloperidol ketone reductase activity, at the beginning and at the end of each period. Blood samples were collected on the same day that clinical assessment were made. Multiple regression analysis (forward stepwise) revealed that Red blood cells reductase activity at D0 is an important variable predicting haloperidol plasma levels at week 2. Similarly Red blood cells reductase activity at D0 and D7 predicted Reduced haloperidol plasma concentrations at week 2. In this sample, no parameter was found to be consistency predicted the percentage change in the PANSS positive subscale from baseline, at week 2. Nevertheless, Red blood cells reductase activity at D0, Reduced haloperidol/haloperidol ratio at week 2, haloperidol plasma levels at week 2 and the dose of haloperidol at week 1 were important variables predicting the percentage change in the PANSS general subscale from baseline at week 2. These results suggest that the knowledge of reductase activity could predict the treatment response in acute schizophrenic patients.

Recent epidemiologic studies (11) have shown a frequency of 3-5% of hyponatremia in chronic psychiatric patients, characterized by headaches, blurry vision, weakness, cramps, vomiting and sometimes seizures or coma leading to death. The etiopathology of this electrolytic syndrome is still debated and intriguing. Six to 17% of hospitalized patients in psychiatry present primary polydipsia, among which 25-50% develop hyponatremia. Another cause is the syndrome of inappropriate secretion of anti-diuretic hormone, SIADH, which may be due to a number of psychotropic drugs as carbamazepine, thioridazine, amitriptyline, desipramine, haloperidol, chlorpromazine and fluoxetine (1, 2, 7, 9, 15, 18, 24). These medications can be associated with primary polydipsia but not necessarily, and the hyponatremia is reversible after discontinuiting the treatment. We describe a case of hyponatremia possibly related to clomipramine which has been rarely reported in the literature and discuss the relations between hyponatremia, psychosis, and SIADH.

Serum levels of haloperidol and reduced haloperidol as well as the reduced haloperidol/haloperidol ratios were determined in nine acute schizophrenics on oral haloperidol medication and correlated over 21 days with psycho pathology and extra-pyramidal symptom scores. We have investigated red blood cells haloperidol reductase activity in the group of patients. Significant correlations were found between haloperidol plasma levels and positive sub scale for each patient (r = 0.86 and p < 0.01; r = 0.70 and p < 0.05). We found a correlation between red blood cells reductase activity and the improvement of the psychotic anxiety scale (r = 0.64/and p < 0.05; r = 0.67 and p < 0.05), but not with reduced haloperidol/haloperidol ratios in plasma. The knowledge of reductase activity could predict the treatment response in acute schizophrenic patients. We suggest that the reported inter individual and inter ethnic differences in haloperidol and reduced haloperidol and in clinical response and adverse effects may be a reflection of genetic control of the two oxidative pathways mediated by cytochrome P450 isozyme and/or the reductase pathway mediated by haloperidol reductase in individual subject.

Extrapyramidal side effects of neuroleptics are important in clinical practice. Study of extra-pyramidal side effects is also of importance for researchers who test new antipsychotic agents or study tardive dyskinesia. A french translation of the Simpson-Angus Rating Scale of extra-pyramidal side effects thus appeared useful. This scale contains 10 items: Gait, Arm dropping, Shoulder shaking. Elbow rigidity, Wrist rigidity, Leg pendulousness, Head dropping, Glabella Tap, Tremor, Salivation. Each item is rated between 0 and 4. A total score is obtained by adding the items and dividing by 10. Scores of up to 0.3 are considered within the normal range. The scale original has been validated in a population of fourteen psychotic inpatients taking, in a double-blind procedure, placebo, haloperidol 6 mg/day or haloperidol 30 mg/day. Patients receiving haloperidol 30 mg/day presented more extrapyramidal symptoms than patients under placebo. The Simpson Angus rating scale has also been shown to have clinical validity and high inter-rater reliability. It can be routinely used in clinical drug evaluation. The french version was used in a population of 30 psychotic inpatients fulfilling the DSM III-R criteria of schizophrenic disorder. Patients were treated for at least two weeks, orally, either with a phenothiazine (chlorpromazine 350 mg) or a butyrophenone (haloperidol 15 mg). 10 of the 30 patients received, in addition, anticholinergic agents (trihexiphenidyl, 5 mg). The french version of The Simpson Angus Rating Scale appeared to be easy to use and not time-consuming. Interraters correlation was high. Patients receiving butyrophenones or phenothiazines had no significantly different ages and sociodemographic characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study is to assess the economic impact of neuroleptic strategies in the long-term treatment of schizophrenic patients. In this respect a new neuroleptic strategy (amisulpride) was compared to a reference drug (haloperidol) using a cost minimization method. Clinical, demographic and economic (direct medical costs) data were obtained retrospectively from patients' charts. Patients (n = 160) were randomly selected according to diagnosis (schizophrenia, DSM III-R), treatment (outpatient, amisulpride or haloperidol) and follow up period (at least 6 months). The health insurance point of view was selected for the economic analysis. We found a significant reduction of the annual number of days of relapse when patients were treated with amisulpride compared to haloperidol. This reduction was associated with a significant reduction of direct costs mainly related to shorter length of hospitalization. This result was only partly explained by demographic and clinical variables such as the severity of the disease. The differences remained significant when populations were matched. This finding illustrates the validity of the concept of efficiency in psychiatry.

Delirium tremens is linked with a chronic depression of the central nervous system by alcohol and a compensatory hyperactivity of neurotransmitters. A sudden stoppage of alcohol intake induces excessive production of these transmitters. Firstly appearing is a noradrenergic hyperactivity which may be responsible not only for reducing the magnesium blood level but also for activating the other transmitter systems. A magnesium blood level lower than 1 mmol.l-1 involves a risk of seizures and requires IV magnesium sulfate. Noradrenergic hyperactivity can be prevented by IV alcohol associated with sedation best achieved by IV clomethiazole in alcoholic solution. Should these preventive measures fail, noradrenaline action in the central nervous system can be blocked by clonidine. Should hallucinations become manifest, linked to dopaminergic hyperactivity, haloperidol is indicated. Benzodiazepines may be useful, particularly carbamazepine, for their depressing effect on gaba-ergic hyperactivity.

We report on a case of Sharp syndrome which was diagnosed late in on 11-year old boy. After 5 years of corticosteroid treatment, he presented with myopericardic aggravation, glomerular disease, and seizures with delirium, which responded to high-dose steroid therapy with early switch using synthetic antimalarial drugs. Six years later the results are still satisfactory.

Biballism is an infrequent hyperkinetic disorder characterized by involuntary, intermittent, violent, uncontrollable contractions of the proximal muscles of the limbs. Biballism is classically ascribed to a lesion in the controlateral subthalamic nucleus or its connections but other causes have been reported. These include infections (bacterial, viral parasitic), cerebrovascular lesions, tumors, toxics, and systemic disease (systemic lupus erythematosus). Although poorly understood, the pathophysiology of hemiballism is widely believed to involve hyperactivity of the dopaminergic system. The prognosis of these abnormal movements, formerly poor, has been improved by the use of neuroleptics and drugs acting on the different neurotransmitter systems. A unique case of biballism at resolution of a febrile coma in a 4 1/2 year old is reported. The EEG showed diffuse slow waves. A hyperdense lesion was visible in the right thalamic region on the cerebral CT scan. The magnitude of the abnormal movements decreased under haloperidol. The etiology of this case of biballism is discussed.

Relying on the ethological model for the collection of data (ethogram), psycholinguistic methods (Cloze procedure, type token ratio) and chronobiological techniques, the present study tests the hypothesis of behavioural, speech and biological ultradian or circadian rhythms in certain types of schizophrenic patients after a 2 week study. Six daily, direct and meticulous 25 minutes observations of the behaviour and speech of four schizophrenics show that stereotyped motor or verbal behaviour does not always fluctuate at random; certain behavioural patterns recur regularly at fixed intervals, according to a set time structure. Most of the behavioural, verbal and biological variables have their acrophase at 10 a.m. and/or at 4 p.m. Instability in the rhythm of the sleep/wake cycle and the oral temperature observed in schizophrenics could be the result of desynchronization of the central pacemakers or of the resynchronization, or even of hypersynchronization with a delay of one phase. It is difficult to ascribe this desynchronization to the illness or the treatment.

A univocal disorder of dopaminergic activity in the nerve structures responsible for extra-pyramidal motility does not take into account the total phenomena seen in psychomotor neurological studies. The hypothesis of two categories of dopaminergic receptors-respectively excitatory (DA) and inhibitory (DAi)--in the striatal and mesolimbic structures concerned, was derived from experimental and clinical anatomical cytological, and pharmacological data. This duality of the receptors could establish a relationship between dopaminergic mediating, mechanism and adrenergic mediation for with the existence of a least two types of distinct receptors, alpha and beta, has been demonstrated. The author discusses the physiopathology of neuromotor disorders wuch as Parkinson's disease, chorea, and various types of dyskinesias, in relation to this dual mediation. By separation of dopamine antagonists and agonists in this new context, it should be possible to have a more selective approach, which would be better adapted, therefore, for the treatment of these affections. The study of the effects of a new medication, tiapride, on dyskinesias provoked by levodopa in parkinsonian patients, is a step forwards in this new method exploration in neurology.

Unlabelled: An open multicentric study of 196 in-patients was carried out in 9 centres. After an initial stabilization (min. 15 days) with oral haloperidol, patients received haloperidol decanoate IM for at least 24 weeks (or a minimum of 9 injections)., Results: - esterification of haloperidol increased the duration of its efficacy (interval between 2 injections: average 4 weeks) without interfering with its therapeutic activity (global appreciation scale, BPRS at each injection and at the end of the treatment); - equivalent quantities of haloperidol injected at a time were 15 to 20 times those administered daily during the initial stabilisation period; - side-effects were not different with haloperidol decanoate as compared to those of the previous period (haloperidol).

We report the results of a comparative study of sultopride and haloperidol in two groups of 46 and 48 patients. The study was single-blind at first, then double-blind. It was carried out at the psychiatric infirmary of the central police station, run according to the law of June 30th, 1938, which allows to detain patients presenting with severe agitation during 24 hours or more for observation and treatment. The target symptom is psychomotor agitation. The purpose is to make a psychiatric interview possible without suppressing all the clinical manifestations or masking the patient's personality. The efficiency of both drugs seems comparable but is better with sultopride given initially in high dosages. As its side-effects are mild and are not aggravated when dosages are increased sultopride is the choice neuroleptic for the initial treatment of psychomotor agitation in patients admitted in the specific conditions of deferred emergencies.

High-dosage haloperidol treatment was administered during three weeks in a rapid neuroleptization technique to fifteen patients suffering from acute psychotic episodes. Haloperidol plasma levels were determined by radioimmunoassay. The efficacy of such a therapeutic design seemed fairly good, particularly the rapid improvement during the first week. Yet, tolerance appeared to be low, with a high incidence of adverse effects, some of them unexpected. A very good correlation was observed between haloperidol plasma levels and haloperidol oral doses. By contrast, there was no correlation between plasma levels and clinical improvement. In the same way, the occurrence of adverse effects did not seem to be related to haloperidol plasma levels.

This is a clinical case report on young female patient aged 30 whom the author has followed with a mixed treatment of psychotherapy and chemotherapy for one and a half year. This patient has a "borderline" symptomatology. The approach through counter-transfer is preponderant. The importance and use of this analysis are emphasized, first to allow a dynamic research of adequate therapeutic attitudes, then to furnish basic knowledge for understanding the type of material and anxiety brought up by this patient. A more comprehensive reflexion is made concerning the situations leading to the use of a first, then second psychotherapeutic drug, in parallel to the psychotherapeutic approach, and to the problems resulting in the therapeutic relationship throughout the transfer and counter-transfer.

The efficacy of i.m. cis(Z)-clopenthixol in aggressive, agitated and delusional patients is well established but it necessitates, as for all other parenteral neuroleptics, several injections daily. Zuclopenthixol acetate is the first injectable neuroleptic characterized simultaneously by a short latency of action (2-3 h) and by a long duration of action (2-3 days). Within the frame of a Belgian multicentre study of zuclopenthixol acetate and haloperidol, a group of French-speaking psychiatrists added the AMDP scales to the basic protocol. The results of this AMDP subsample of 20 Acetate vs. 13 Haloperidol patients do not allow the demonstration of statistically significant differences between both neuroleptics because of the smallness and unbalance of the sample, but they indicate that both antipsychotics are very active and that a comprehensive rating scale such as the AMDP gives a much better differentiated clinical picture of a new drug than the total scores of short, so-called "economical" rating scales.

The problems encountered during the longterm treatment of psychotic patients with neuroleptics are illustrated by six typical case reports. A group of patients who had had a new acute episode despite seemingly adequate treatment were selected. In these six cases it was demonstrated that the neuroleptics dosage was inappropriate, being either too high or too low as judged from the plasma concentrations. Ways of improving the adequacy of the treatment of psychotic patients with neuroleptics are discussed.

The effect of high doses of haloperidol on the clinical status, plasma neuroleptic and prolactin concentrations as well as on CSF HVA and GABA levels was investigated in 3 paranoid schizophrenic patients over a 6 weeks period. When the study was initiated patients had been on haloperidol (10 mg a day) for 4-10 weeks. Oral doses were increased at weekly intervals from 10 (day 0) to 100 (day 7) and 200 (days 14 to 28) mg a day and then reduced to 100 (day 35) and 10 (day 42) mg/day. A linear relationship was observed between plasmatic levels and daily doses of haloperidol. In neither patient, the increase in haloperidol dosage affected paranoid symptoms. Neurological side effects were slightly increased in 2 cases and moderately reduced in one case. Prolactin plasma levels, already high at the onset of the study rose when increasing the dose to 100 mg a day but did not increase further despite increment in the haloperidol dosage. CSF levels of HVA and GABA rose from day 0 to day 7 but were back to the initial values on day 28 in 2 patients and were decreased from day 0 to day 28 in one patient. For the 3 patients a close correlation was observed between changes in CSF HVA and GABA levels. It is concluded that high doses of haloperidol, although causing biochemical changes compatible with the occurrence of dopamine target cell supersensitivity, do not lead to any clinical improvement in the 3 studied schizophrenic patients.

The authors have studied the action of high doses of Haldol in chronic schizophrenics in a study lasting more than five months and compared their results to a study done at the Eastern State hospital of Williamburg in Virginia (U.S., Howard). The daily doses of 75 mg caused a remission in 4 schizophrenics, and 19 patients were improved in a sample of 38 patients. The medication was given to a group exposed to neuroleptics only, without differences between the two groups. The authors have carried out the study for more than one year without observing changes in biological tests, using a dayly dose of 60 mg. Five patients out of nine were improved and could be discharged to return to their family or society with the appropriate affective follow-up.