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P M Llorca

Publications and source records attributed to P M Llorca.

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PubMedDate not supplied

[Acute schizophrenia concept and definition: investigation of a French psychiatrist population].

For schizophrenic disorders, the clinical conception of "acute state" is widely used in clinical settings to assess the effectiveness of therapeutic programs as well as epidemiological studies. Schizophrenic-specific symptomatology modification, need for hospitalization, significant change in care, disturbances in social behavior or suicide attempts were all used to define acute schizophrenic state. The decision to hospitalize is frequently used to define acute state but refers to multiple factors such as mood disorder, suicide attempts, drug abuse or social and environmental problems. Indeed, several and distinct definitions in a criteria basis form are available but no one has reached consensus. Because recognition of acute schizophrenic state remains based on the subjective clinician's advice, epidemiological and therapeutic studies fail in validity and reliability. The aim of the study was to evaluate how a population of French psychiatrists define criteria and therapeutic targets of acute schizophrenic state in their clinical practice. Psychiatrists filled out a self administered interview. At the time the interview was given, clinicians were notified that they were participating in a clinical consensus survey about schizophrenia. Six major indicators for acute state definition based on the literature data were proposed: general schizophrenic symptomatology modification (depression, anxiety, agitation, impulsivity/aggressiveness), specific schizophrenic symptomatology modification (positive symptoms, negative symptoms, disorganization), need for hospitalization, significant change in care, disturbance in social behavior and lastly, suicidal behavior. Minimal duration (1.2 or 4 weeks) of general and specific schizophrenic symptomatology modification required to define acute state were evaluated. The booklet included the 30 PANSS symptoms listed with their definitions. Among this symptom list, clinicians were instructed to select the ten criteria which they estimated best defined the acute state, followed by the ten most important target symptoms to be treated. Out of 2,369 questionnaires, 1,584 were collected on time (66.9%). Among the six majors indicators proposed to define acute state 75% of psychiatrists considered 1 to 3 criteria. Three were more frequently rated, including core schizophrenic symptomatology disturbance (68.4%), general schizophrenic symptomatology disturbance (68.0%) and suicidal behavior (64.9%). The other criteria were rated as follows: need for hospitalization (26.8%), significant change in care (18.3%), and disturbance in social behavior (29.1%). For 53.2% of psychiatrists the definition of acute state requires the presence of specific schizophrenic symptomatology for a minimal duration of one week. Two weeks with general symptomatology was required for 45.5% of psychiatrists to define acute state. Symptoms more often rated within the four first choices for acute state definition included delusions, conceptual disorganization, hallucinatory behavior and excitement. Except for grandiosity, all the PANSS positive subscale items were chosen to be included in the definition (delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution and hostility). Four items, including anxiety, depression, uncontrolled hostility, inner tension from the general psychopathology subscale were chosen as part of the ten most important criteria to define acute state. On the PANSS negative subscale (blunted affect, emotional withdrawal, poor relationships, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity/flow of conversation and stereotyped thinking), no item was rated to be included in the acute state definition. The highest rated symptoms among the four first choices for treatment included delusions, hallucinatory behavior, excitement and anxiety. The ten most important criteria for treatment were the same as for acute state definition with differences in frequency. Excited state, depression and suspiciousness/persecution were more rated for treatment than definition whereas delusion, hostility and conceptual disorganization were less rated as treatment target than definition criteria. In clinical practice, recognition of acute schizophrenic state is underscored by the association of specific schizophrenic symptomatology (positive symptoms, negative symptoms, disorganization) and general symptomatology (impulsivity/aggressiveness, anxiety, depression, agitation) of schizophrenia. For most clinicians, acute state definition requires specific symptom for a minimum of one week and other non-specific indicators such as suicidal behaviour have to be taken into account. With regard to PANSS criteria, most positive schizophrenic symptoms and some general schizophrenic symptoms are necessary for definition and designated as treatment priorities. Negative symptoms were not taken into account. Hallucinatory behavior is the first symptom rated in definition and is considered by psychiatrists as the absolute therapeutic priority. This survey could be a first step in the construction of an operational and consensual definition. This definition is strongly needed as a valid measurement in therapeutic and epidemiological outcome studies, which remain at least partly based on clinician subjective judgment.

Acute Disease↗
PubMedDate not supplied

[Cost-effectiveness analysis of schizophrenic patient care settings: impact of an atypical antipsychotic under long-acting injection formulation].

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)

Antipsychotic Agents↗
PubMedDate not supplied

[Escitalopram for treatment of major depressive disorder in adults].

Escitalopram is a selective serotonin reuptake inhibitor (SSRI); it is the therapeutically active S-enantiomer of the racemic mixture, citalopram. This review aimed to compare the efficacy and tolerability of escitalopram versus citalopram and several other SSRIs (citalopram, fluoxetine, paroxetine, sertraline), and a selective reuptake inhibitor of noradrenaline and serotonin, venlafaxine XR, for treatment of DSM IV (Diagnostic and Statistical Manual of mental disorders - fourth edition) major depressive disorder, based on the studies evaluated by the Commission de la Transparence de la R6publique Frangaise, and data from a pooled analysis presented in 2005 at the 158th annual congress of the American Psychiatric Association. Change from baseline to end-point on total MADRS (Montgomery-Asberg Depression Rating Scale--10 items, score range: 0-60) was the primary efficacy parameter; changes on HAM-D17 (Hamilton rating scale for depression--17 items), CGI-S and CGI-I (Clinical global Impression-Severity and-Improvement), and response rates (> or = 50% MADRS score reduction) and remissions (< 12 MADRS score) were the secondary efficacy parameters. Tolerability assessment was based on the numbers and rates of adverse events observed with treatment, and the DESS (Discontinuation Emergent Signs and Symptoms-43 items) scale was used for assessment of adverse events observed with treatment withdrawal. Analyses were based on intention to treat using the LOCF (last observation carried forward) method. Efficacy of escitalopram appeared to be at least equivalent to that of the active comparators in all cases. The difference between active compounds was more marked when depressive symptoms were more severe. From the point of view of tolerability, frequency of adverse effects occurring on treatment and the frequency of treatment discontinuations due to adverse effects were comparable with both escitalopram and the active comparators; however, the comparisons were mostly favourable to escitalopram, though differences were generally not statistically significant. In both studies of escitalopram versus venlafaxine XR, treatment discontinuations due to adverse events were less frequent on escitalopram than on venlafaxine XR (7.5% vs 11.2%, and 4.1% vs 16.0% respectively). With regard to adverse events associated with the withdrawal period, the signs and symptoms occurring on treatment discontinuation assessed after 1 week using the DESS scale were less frequent on escitalopram than on venlafaxine XR at 8 weeks and paroxetine at 24 weeks. Concerning suicide risk, a review of clinical trials involving 2277 patients on escitalopram and 1814 patients on placebo showed that this risk was minimal, and similar in both groups; moreover, no evidence was found suggesting that escitalopram might promote suicidal behaviour compared with placebo. These results suggest that escitalopram is suitable to be considered as a first-line drug treatment for major depressive disorder.

Adult↗
PubMedDate not supplied

[The concept of supersensitivity psychosis. The particular case of clozapine].

Neuroleptics are the main biological treatment for psychotic patients. The brutal withdrawal of a neuroleptic treatment may induce an important aggravation of the psychotic symptoms. A few of those relapses may occur very early after the interruption of treatment; they are often associated with a modification of the symptoms and an unfavorable evolution in the course of the illness. Using those clinical observations a few authors have developed the concept of supersensitivity psychosis to explain those kinds of relapses and to formulate hypothesis about tolerance and resistance to neuroleptics. They focus on the possible correlation between supersensitivity psychosis and tardive dyskinesia. We report three cases of a dramatic aggravation of the psychotic symptomatology following the withdrawal of clozapine in three schizophrenic patients resistant to classical neuroleptic treatment. According to the clinical data and to the physiopathological hypothesis, the concept of supersensitivity psychosis can have implications in the therapeutic management of resistant schizophrenic patients.

Adult↗
PubMedDate not supplied

[Clozapine in the treatment of refractory rapid cycling bipolar disorder].

A 42 years old man suffering from bipolar disorder I with rapid cycling, unresponsive to conventional therapy, was successfully treated with clozapine. The plasma clozapine levels were monitored. This case suggests that clozapine could be efficient in treating mania and preventing relapse in affective disorders. The plasma concentration of clozapine is discussed.

Adult↗
PubMedDate not supplied

[Evaluation of the quality of life of schizophrenic patients: validation of the brief version of the Quality of Life Interview].

UNLABELLED: The main objective of the study was to determine the psychometric properties (mainly, validity and reliability) of the French language version of the brief Quality of Life Interview (QoLI). That instrument evaluates both the subjective and objective aspects of quality of life. METHODS: 128 patients fulfilling the DSM IV criteria for schizophrenia were included. Quality of life was evaluated using the brief QoLI. Schizophrenic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). The validity of the internal structure of the QoLI was investigated by means of item analysis, study of the correlations between the items and between the item-dimensions and principal component analysis addressing the subjective fields. The validity of the external structure was mainly investigated through the nomological validity study. The reliability of the scale was evaluated by studying the internal consistency. In addition, the acceptability of the scale was documented. RESULTS: The results of the study of the validity of the internal structure confirmed the pertinence of the pre-defined fields, particularly the subjective fields. Only some of the subjective fields of the QoLI showed significant correlations with the PANSS sub-scales. The acceptability of the scale was satisfactory. CONCLUSIONS: The psychometric properties of the French language version of the brief QoLI appeared satisfactory. The brief QoLi was shown to be an easily used instrument for assessment of the various objective and subjective aspects of the quality of life of schizophrenic patients.

Adult↗
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[Pharmaco-epidemiological study on antipsychotic drug prescription in French Psychiatry: Patient characteristics, antipsychotic treatment, and care management for schizophrenia].

UNLABELLED: In 2000, a one week national survey was conducted among 202 psychiatrists (129 participants) in France, from hospitals and clinics, private or public. The first 20 inpatients and 10 outpatients prescribed at least one antipsychotic drug (age range 18-65), were included. The diagnostic procedure was standardized with a structured interview: the Mini International Neuropsychiatric Interview (MINI). A total 2 068 patients were included, among whom 892 (43.1%) reached the criteria of schizophrenia according ICD-10. We present here data on these latter patients. Mean age was 38.8 years; with 38.8% females. Median duration of current antipsychotic treatment was 0.5 year in inpatients and 2 years in outpatients. Median duration of any antipsychotic treatment was 10 years, without difference between groups. Comorbid situations (anxiety disorder, depression and suicidal risk) were found in 33.1% of schizophrenic patients, with higher frequency among inpatients in private hospitals (54.8%) than in other groups. 46.8% patients were prescribed at least 2 neuroleptics, and 73.6% at least one non-neuroleptic drugs. Cyamemazine accounted for 16.6% of all neuroleptics drugs, and 56% of patients were prescribed an atypical antipsychotic (risperidone, olanzapine, amisulpride or clozapine). Atypical drugs accounted for 59.4% of patients who were prescribed only one neuroleptic drug. Inpatients had more neuroleptics coprescription than outpatients (mean 1.8 vs 1.4 drugs), with higher daily dose. In addition, inpatients had more other psychotropics prescribed (mean 1.5 vs 1.1 drugs). Overall, more other psychotropic drugs were prescribed among patients with -, than those without - comorbid situations (1.7 vs 1.2 drugs). Median time since admission, at the time of the study, were similar in private and public hospitals (107 vs 99 days) but maximal time since admission was respectively 2.8 and 48.9 years. Visit frequency for outpatients was more than one every two weeks for 43.1% in private and 24.7% in public clinics. Among inpatients only we found a difference between private and public hospitals for polypharmacy of non neuroleptics psychotropics, (mean 1.9 vs 1.5). In outpatients, long acting depot accounted for 26.6% of neuroleptics treatments in public clinics and 15.4% in private clinics. Finally, we found that polypharmacy among outpatients increased with duration of antipsychotic treatment. CONCLUSION: in France, important differences are reported in antipsychotic prescription for schizophrenia between in- and outpatients. Current antipsychotic prescription is more recent in inpatients than in outpatients, with similar duration of overall antipsychotic treatment. Inpatients have more drug prescription, antipsychotics and other psychotropics, than outpatients. Differences are less important between private and public providers. Inpatients in private hospitals receive more non neuroleptic drugs than in public hospitals, and depot antipsychotics are more used among patients of public clinics. Long term inpatients are found in public hospitals only. Outpatients follow up is more intensive in private than in public clinics.

Adolescent↗
PubMedDate not supplied

[Compliance in schizophrenia: predictive factors, therapeutical considerations and research implications].

Compliance has been defined as the extent to which a person's behavior coincides with the medical advice given. Medication compliance is one of the foremost problems affecting neuroleptic efficacy in psychiatric patients. Since chlorpromazine introduction in 1952, antipsychotics are the principal element of schizophrenia treatment. Actually progress links to the use of new antipsychotics are conditioned by quality of compliance. The problem of nonadherence to medication could concern 50% of prescription. The reported incidence of non-compliance with antipsychotic medication ranges from 11 to 80%. In a two thirds of case rehospitalization is the result of complete or partial noncompliance. After one year of first hospitalisation, 40% of relapse results from non adherence to medication. Medication adherence problems increase hospitalisation, morbidity and mortality. Social consequences, professional problems and family troubles linked to hospitalisations lead to low quality of life for patients and high cost for society. There are three main methods of measuring compliance. These include patient and clinical self-report, pill counts, and biological measures. Self-report methods are generally the most cost-effective and time-efficient way of obtaining an indication of compliance. In psychiatric research, the most commonly used self-report measure of compliance is the Drug Attitude Inventory (DAI) originally devised by Hogan et al. On the basis of criticism concerning DAI reliability, a new questionnaire of medication compliance was proposed: the Medication Adherence Rating scale (MARS). The main goal of compliance evaluation is to quantify this phenomenon with accuracy and to find predictive factors of medication nonadherence. Three types of factors influencing compliance are identified: factors due to medications, factors linked to patients and factors depending on the therapeutic relation with the clinician. Tolerance is considered as the principal reason explaining a bad compliance. Neurologic, endocrine and anticholinergic side-effects are the first fact of treatment stop. Medication prescription complexity is although important to take under consideration. Some psychotic's symptoms, comorbid addictive behavior, poor insight are mentioned in the case of noncompliance. Some effective actions to improve compliance are described. Information and communication with the patient, simplification of therapeutic plan, consultation planning and account of side effect are simple and effective actions. Social support is very important for improvement of compliance. The communication attitude of the clinician, therapeutic relation and prescription use are main points of compliance. Compared to a conventional care, psychoeducational programmes of compliance show their superiority. More research on compliance evaluation is needed. Information and tools must be proposed to practitioners.

Antipsychotic Agents↗
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[Neuroleptic-induced movement disorders: historical perspectives].

Soon after the discovery of neuroleptics, neurological side effects of the extrapyramidal type were reported. The first description of neuroleptic-induced parkinsonism dates back to the "Swiss Symposium on Chloropromazine" held in 1953. Steck in 1954 vividly described the symptoms in a convincing manner. In 1955, Delay and Denicker, observing the therapeutic efficacy and extrapyramidal activity of two seemingly different compounds as chloropromazine and reserpine, used the term "neuroleptic" to characterize this common property. Two years later they proposed a definition of neuroleptics taking into account therapeutic efficacy as well as side effects. Such a definition was not accepted by American authors who preferred term like "major tranquilizers" and finally "antipsychotics". The meaning of neuroleptic parkinsonism (whether it was a side effect or part of the therapeutic action) had been discussed for a long time. The analogy with the clinical manifestations of Von Economo's encephalitis lethargica was also mentioned. Tardive dyskinesia appeared in the literature in the late 1950's. The first report was made by Schoenecker in 1957 who described bucco-oral movements persisting after the neuroleptics were diminished or discontinued. He concluded that these manifestations were different from the acute extrapyramidal side effects. Two years later Sigwald et al. reported involuntary movements of the tongue, lips and facial muscles which appeared after several years of phenothiazine treatment. In 1960 Uhrbrand and Faurbye described bucco-linguo-masticatory movements sometimes associated with trunk and foot movements. Half of these cases persisted (and a few aggravated) after neuroleptic withdrawal. In others the condition was unmasked by the neuroleptic discontinuation. In 1964 Faurbye et al. proposed the term "tardive dyskinesia" for this extrapyramidal side effect. After an initial description by Druckman et al. in 1962, the term of "tardive dystonia" was first used in 1973 by Keegan and Rajput. The patients described in the early literature were mainly of an advanced age with organic involvement. The first serious epidemiological studies were undertaken in the late 1960's, showing prevalences varying between 0.5 to 65%! Most of the predisposing factors suspected in early studies (cerebral lesions, lobotomy, ECT) were not confirmed in more recent studies that emphasized the role of an older age and a female gender. The interest in tardive dyskinesia varies from one country to another. Perhaps, dyskinesia was more severe and problematic in the USA because of more liberal indications for neuroleptic use, higher doses and smaller choice of neuroleptic medications. Medicolegal aspects have also increased the apprehension of american physicians. Tardive dyskinesia remains an enigmatic phenomenon and a therapeutic challenge. In the future, the possible discovery of antipsychotic molecules devoid of extrapyramidal side effects may discourage the research on these unresolved issues.

Antipsychotic Agents↗
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[Descriptive approach to latent forms of schizophrenia].

The computerized medical file, used in routine work in an Adult Psychiatry University-Hospital Unit enabled us to select 113 cases among 1,000 consecutive hospitalizations, the diagnosis of which could possibly lead to schizophrenia. These cases which we named "paraschizophrenic states" are linked to DSM III-R criteria of borderline (27 cases), schizoid (40 cases) or schizotypical (15 cases) personalities, schizophreniform trouble and unspecified psychotic trouble (17 cases), brief reactional psychosis (14 cases). We selected 196 cases of schizophrenia in the same cohort of hospitalized patients. As it is now usually admitted, we marked out two subgroups in this second group: the positive schizophrenia which gather together the paranoid and undifferentiated patterns and the negative schizophrenia which correspond to disorganized, catatonic and residual models, according to DSM III-R criterion. We compared the "paraschizophrenic states'" group and its five subgroups (we indeed joined schizophreniform trouble and unspecified psychotic trouble under the name of "other psychotic trouble" by reason of their relative nosographic lacks of precision and of their too small sizes) with the schizophrenia's group and its two subgroups. Each group is matched for sex (1.51 men for 1 woman in the first group and 1.45 men for 1 woman in the second group). We evaluated statistics for markers usually studied in schizophrenia in each subgroup. These markers are of three classes: biographical: age during the study, age of troubles' onset, season of birth; socioeconomic: socioeconomic level of family and patient's student status; psychiatric: family (history affective trouble, psychotic trouble, alcoholism), treatment response and short- and middle-term prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

[Comparative efficacy of bromocriptine, carbamazepine and cyproheptadine with neuroleptics in 24 refractory chronic schizophrenic patients].

Different drugs have been used as adjuvant to neuroleptics in chronic schizophrenia. Bromocriptine, carbamazepine and cyproheptadine have shown an efficacy added to neuroleptics in schizophrenia. In our study, 24 chronic schizophrenic inpatients considered to be resistant to neuroleptics were treated double blind with the associations haloperidol (40 mg a day)--carbamazepine (400 mg a day), haloperidol (40 mg a day)--bromocriptine (2.5 mg a day), haloperidol (40 mg a day)--cyproheptadine (24 mg a day) and haloperidol (40 mg a day)--placebo. The drugs were given successively, in a randomized succession using a latin square procedure, for four 5-weeks periods. A psychiatric assessment using the Brief Psychiatric Rating Scale (BPRS), the SANS (Scale for Assessment of Negative Symptoms) and the SAPS (Scale for Assessment of Positive Symptoms) occurred every two weeks. Extrapyramidal symptomatology and abnormal movements were assessed using the AIMS (Abnormal Involuntary Movement Scale) and the Simpson-Angus scale. Using an ANOVA, we cannot show any clinical efficacy of any of those three drugs as an adjuvant to haloperidol. The discrepancy between our results and the data of the literature can be linked to the high specificity of our sample (resistance to neuroleptics). We cannot show any specific efficacy of those drugs on positive and negative symptoms, using the sub-factors of the SAPS and SANS.

Adult↗
PubMedDate not supplied

[Clinical effects of clozapine: effect on negative symptoms].

OBJECTIVES: we have realized an open study in a population of chronic schizophrenic inpatients treated with clozapine. The purpose of this study was to investigate the clinical response and the effect of extrapyramidal symptoms of this atypical antipsychotic. METHODS: our sample is composed of 25 chronic hospitalized schizophrenics (18 males, 7 females; average age = 36.57, SD = 8.41) with an initial important symptomatology (average score on BPRS = 64.92, SD = 7.99). The weekly assessment was done using PANSS and EPRS during 9 weeks. After a 15-days period of treatment adjustment, each patient reached a daily dose of 400 mg. Then the dosage was adjusted according to the clinical condition of the patients (average = 429.41 mg per day). RESULTS: using the PANSS, we identified a statistically significant (p < 0.05) clinical improvement from the fourth week of treatment for global score, positive, negative and general psychopathology sub-score. For EPRS a dramatic improvement (p < 0.01) occurred from the second week. We found no correlation between the improvement of negative symptoms and the improvement of extrapyramidal symptoms. We individualized a sub-group of 7 good responders who showed an improvement of 20% or more on PANSS global score at the ninth week. This group showed a statistically significant (p < 0.01) more intense initial negative symptomatology compared to non-responders. CONCLUSION: the improvement of extrapyramidal symptoms precede the improvement of psychotic symptoms; this effect underlines the good neurological tolerance of clozapine. The clinical efficacy concerns both positive and negative symptoms. The efficacy on negative symptoms seems to be primary. In our sample, patients with intense negative symptomatology improve more than others.

Adolescent↗
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[Psychometric properties of PANSS (Positive and Negative Syndrome Scale) in the French version in a sample of schizophrenic patients].

Our study focuses on psychometrics properties of the french version of the Positive and Negative Syndrom Scale (PANSS). 85 schizophrenic subjects, in accordance with DSM III-R criteria were included in this study. Our results allow us to discuss the construct validity and the reliability of this scale. The traditional 3 dimensions of the PANSS (positive, negative and general psychopathology) are discuss. We show that expect positive scale and general psychopathology scale average several symptomatic dimensions. We propose a 5 dimensions solution (negative, hostility, positive, disorganization, anxiety), which represent 54% of the total inertie. The internal consistency of this solution is presented.

Adolescent↗
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[Psychoses, mood, suicidal tendencies and clozapine].

Depression and mood disorders are frequently associated. They can be described as a part of schizophrenic symptomatology, observed as post-psychotic depression, be a part of a schizoaffective disorder or be a consequence of neuroleptic treatment. Suicide is the main risk of evolution in young schizophrenics and is often associated to depression. Despite methodological difficulties, a few studies demonstrate the efficacy of clozapine, one of the first atypical antipsychotic, in the treatment of depressive symptomatology in schizophrenics and schizoaffectives. This action remains controversial in the treatment of post-psychotic depression. This drug also contribute to reduce suicidality in a sample of chronic schizophrenics in an open study. This action has to be considered when we evaluate the risk-benefit of the prescription of clozapine.

Antipsychotic Agents↗