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The development of early intervention in psychotic disorders has allowed a more optimistic approach and the development of more adapted and more efficient treatments. Primary care practitioners are often the first professional contact for patients developing psychosis, but diagnostic difficulties and patients' reluctance to engage in treatment are often an obstacle to private practice treatment. It is therefore important to provide more information to primary care practitioners on specific characteristics of these disorders and about locally available treatment structures in order to allow them to suspect this relatively rare diagnosis, facilitate the collaboration with flexible and accessible specialist services, that ideally should provide home treatment, and to improve prognosis.

Introduction: Previous studies comparing olanzapine (OLZ) and risperidone (RIS) have tended to focus on multiple-episode patients, with no studies examining their comparative efficacy in a non-selective sample of first-episode psychosis., Methods: The Early Psychosis Prevention and Intervention Centre in Australia had admitted 786 first-episode psychosis (FEP) patients between 1998-2000. Data were collected from the medical records (MR) of 367 patients, which met inclusion criteria. The primary objective was to evaluate the efficacy of OLZ vs. RIS as measured by CGI-S, CGI-BP (symptomatic level), GAF and SOFAS (functioning level)., Results: 367 FEP patients were entered into the study, 278 in the RIS- (2.7 mg/day) and 89 in the OLZ group (10.2 mg/day). No between-group differences were found in non-affective FEP (n = 273). In affective FEP patients (n = 94), mainly treated for acute mania (86.7 %), OLZ treatment was related to better response on the symptomatic (CGI-S; p = .002), but not on the functioning level (GAF and SOFAS; ns). There were trends in the OLZ group towards a higher rate of remission of positive symptoms ( p = .054) and a shorter treatment duration to reach this remission in affective FEP patients ( p = .077). More extrapyramidal side effects ( p <.001) were related to RIS and more weight gain to OLZ-treatment ( p <.001)., Discussion: Despite the limitations of a retrospective MR design, study results suggest equal therapeutic efficacy of OLZ and RIS in non-affective FEP and some therapeutic advantages of OLZ compared to RIS in affective FEP patients, especially in those with acute mania. Results may serve as hypotheses for future randomised controlled trials.

Objective: Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross-sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms., Method: The Early Psychosis Prevention and Intervention Centre admitted 786 first-episode psychosis (FEP) patients between 1998 and 2000. Data on SUD and clinical outcome were collected from patients' medical records (MR) of 643 patients who met inclusion criteria., Results: Lifetime prevalence of SUD was 74%, with 62% having a SUD at baseline. This reduced to 36% in those patients who completed 18 months of treatment at the EPPIC program. A Cox regression analysis indicated that a decrease or cessation of substance use significantly increased the probability of remission, whilst persistent SUD substantially reduced the likelihood. In addition, patients who reduced use appeared to have better outcomes at 18 months than those patients who had never used substances. Baseline SUD was not found to have any significant influence on symptom remission., Conclusion: Patients presenting with FEP have high rates of SUD. Effective management of psychosis within a specialized service is associated with reductions in SUD over the course of treatment, although persistent substance use is associated with non-compliance, treatment drop-out and poor remission rates. As such, young people with FEP and comorbid substance use should be offered integrated treatment that addresses both disorders., (Copyright Blackwell Munksgaard 2005.)

Objective. Investigation of the efficacy and tolerability of olanzapine (OLZ) as second-line treatment in subjects with a first-episode psychosis (FEP) who had been non-responsive, intolerant or non-compliant to Risperidone (RIS). Methods. The Early Psychosis Prevention and Intervention Centre in Melbourne admitted 786 FEP subjects between 1998 and 2000. Data were collected from subjects' medical records (MR). The objective was to evaluate the efficacy of OLZ as measured by CGI-S, GAF, SOFAS and remission rates as well as tolerability. Results. A total of 104 subjects were switched because of non-response (38%), non-compliance (15%), or intolerance (47%). Independent of reasons for switch, significant symptomatic and functional improvements were detected. Overall, 46 subjects (44%) achieved full remission. Regression analysis indicated that reason for switch did not predict full remission. Significantly more extrapyramidal side effects (P<0.001) were related to previous RIS and significantly more weight gain to the subsequent OLZ treatment (P<0.001). Conclusions. OLZ may be an effective alternative for FEP patients who are non-responsive, intolerant or non-compliant to RIS. The decision to switch to OLZ must be weighted against the greater risk of weight gain with its risks for medical complications and its psychosocial consequences.

Objective: (1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence., Methods: The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment., Results: The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects., Conclusions: All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Background: The validity of a sub-classification of affective psychosis according to the mood congruence of psychotic features has been questioned in the literature. While some authors have found a correlation between such symptoms and outcome, their predictive value was rather limited in these studies., Method: Prospective study of 108 subjects presenting with a first DSM-III-R manic episode with psychotic features to determine the frequency of different types of psychotic symptoms and to measure the predictive utility of mood incongruent psychotic symptoms (MIPS) and first-rank Schneiderian symptoms (FRSS) during the first episode for a 12-month outcome. Outcome was measured by the level of positive, negative, depressive symptoms, and psychosocial functioning. Duration of affective and psychotic symptoms was also assessed., Results: Patients presented with a wide variety of psychotic symptoms. The presence of MIPS at baseline was significantly correlated with a longer persistence of psychotic symptoms, but not with poorer outcome at 12 months. By contrast, the presence of FRSS at baseline was significantly associated with earlier onset of psychosis as well as increased severity of negative symptoms and poorer psychosocial functioning after 12 months., Conclusion: The presence of FRSS during a first manic episode with psychotic features identifies a sub-group of patients with more severe presentation and poorer short-term outcome. These results question the prognostic utility of MIPS., Limitations: Despite the relatively large number of subjects compared with other studies, the statistical power to detect all but large effect sizes is limited by the sample size.

Psychotic patients to not access easily to psychiatric care. First, psychotic disorders are difficult to identify among a great number of non psychotic depressive and anxious disorders. Second, inpatient care has shortened and now focus on acute care rather than long stay. For some psychotic patients, desinstitutionalization means exclusion and marginalization. Intensive case management can answer these needs in collaboration with relatives and professionals of patient's social network. Results and care's steps of intensive case management as practiced in Lausanne are described and illustrated with cases vignettes.

Schizophrenia has long been considered with pessimism, but the recent interest in the early phase of psychotic disorders has modified this often unjustified perception. Literature has demonstrated the benefit of the development of programs specialised in the treatment of early psychosis, which tend to be developed in many countries. It is however important to match them to local needs as well as to the structure of local health services. This paper reviews elements that justify such a development in Lausanne, Switzerland, and describe its various elements.

Substance abuse co morbidity is frequent in psychotic disorders. General practitioners are frequently involved in such treatments. In order to be able to face this complex task, it is important to be able to identify early symptoms of psychosis in a patient abusing substances, to make the difference between psychotic symptoms and intoxication or withdrawal symptoms, to know basic principles of treatment and the type of medication used in such interventions, and finally to know when specialised treatment or hospital admission are required. This paper reviews epidemiological and diagnostic elements, outlines the various treatment stages, the type of medication currently used in such situations and provides a brief description of motivational interview techniques.

Background: The feasibility of clinical trials depends, among other factors, on the number of eligible patients, the recruitment process, and the readiness of patients to participate in research. Seeking patients' views about their experience in research projects may allow investigators to develop more effective recruitment and retention strategies., Methods: A total of 100 patients consecutively admitted to a psychiatric university hospital were interviewed with respect to their willingness to participate in a study. For a different study scenario, patients were asked whether they would be ready to participate if such a study were organized in the service and to indicate their reasons for refusing or for participating., Results: The general readiness to participate in a study ranged between 70% and 96%. The prospect of remuneration did not notably augment the potential consent rate. The most common and spontaneous motivation for agreeing to take part in a study was to help science progress and to allow future patients to benefit from improved diagnosis and treatment (87%). The presence or lack of a financial incentive was rarely chosen as an argument to agree (23%) or to refuse (7%) to participate. Patients relied mainly on their treating physicians when contemplating possible participation in a study (family physician [65%] and hospital physician [54%])., Conclusions: Clinicians and, in particular, treating doctors can play an important role in facilitating the recruitment process.

Early intervention in psychosis has attracted more attention in the last few years. The treatment of this phase of the disorders requires a specific and adapted approach. The issue of engaging the patient is so critical that it influences not only the choice of medication, but also the context and the way in which it is administered. In the case of a first admission, patients should be observed for 24-48 h without any antipsychotic treatment, in order to clarify the diagnosis and exclude the possibility that symptoms are caused by acute intoxication with illicit substances, for example. The diagnosis is often difficult and unstable. A dimensional, rather than a categorical approach, is usually more likely to be adopted. In recent years, atypical antipsychotics have become the most frequently used first-line treatment. They are less likely to cause secondary negative symptoms, cognitive impairments and dysphoria. They also appear to influence the course of depression and hostility/aggression better than conventional neuroleptics, have possibly mood-stabilising properties and, subjectively, are often better accepted by patients. On the risk side, prevalence of acute extrapyramidal side effects and possibly tardive dyskinesia are lower, compared to the older neuroleptics. Although, the risk for short-term weight gain, cardiovascular, and especially hyperglycaemic complications are somewhat higher for some of these antipsychotics. Finally, the dose should be adapted as it has been shown that patients presenting a first psychotic episode respond to a lower dose of antipsychotic. This article focuses on the pharmacotherapy of first-episode psychosis, on the basis of a computerised and a manual search for articles dealing with antipsychotic treatment of these patients. Findings are discussed and combined in clinical guidelines for first-episode affective and non-affective psychosis, for patients with incomplete recovery or treatment resistance, for cases of emergency and for side effects associated with antipsychotic treatment.

Objective: While first-episode (FE) psychosis has become an important field of research, FE affective psychoses, and mania in particular, have been relatively neglected. This paper summarizes current knowledge about FE mania and explores the potential for early intervention., Method: The main computerized psychiatric literature databases were accessed., Results: When functional as well as symptomatic variables are considered, the outcome of mania is not as good as was formerly believed, a characteristic which is already present from the first episode. Various factors (lower socio-economic status, younger age at onset of illness, poor adherence to treatment, presence of comorbidity) have been identified as possible predictors of poor outcome. The prognostic value of the presence of psychotic symptoms and their congruence to mood, as well as the diagnostic subgroup, is less well established. This literature review also reveals striking similarities between manic and schizophreniform first episodes. Poor functional outcome in a significant proportion of patients following the first episode, high risk of suicide, high prevalence of comorbid diagnoses, worse outcome with a younger age at onset and with longer delay until treatment is initiated, and finally early presence of neuro-anatomical changes, are observed in both syndromes., Conclusions: This pattern justifies the development of early intervention strategies for FE manic patients and supports more exploratory research to identify prodromal symptoms, which might ultimately lead to even earlier focus on preventive interventions.

Practice of psychiatric hospitalization has considerably changed: deinstitutionnalization, brief hospitalizations, opened units, partnership with patients and complementarity with community mental health services. These changes appear simultaneously in most of industrialized countries. They are the result of social changes, evolution of mental health care, and a sharper perception of deinsertion risks through long term hospitalizations. Values of psychiatric hospital were based on a closed and protective place, where community life prepared to life in the community; they are now founded on an opened place where care aims at resolving crisis and keeping closely in touch with the community. These modifications imply to rethink hospital psychiatric care and their connections with environment. This paper describe a model of care developed in a first admission psychiatric unit.

While the hospital remains an important element of the psychiatric health-care system, the fact that it is always the best place to treat acute psychotic episodes is still debated. After a brief review of the literature relative to the main existing community care models, the authors describe the development in the Department Universitaire de Psychiatrie Adulte (DUPA), of an alternative to hospitalisation for patient going through a severe acute psychiatric episode. They present three clinical situations and the aims of the research project, which will follow this pilot phase.

Unlabelled: Subjective response to neuroleptics is essential to long term observance of treatment and quality of life of patients. Numerous factors (pharmacological, relational and psychopathological) are responsible of this subjective response. Objectives of this study are: (a) to examine psychometric features of the french version of the Drug Attitude Inventory (DAI-30) [13] and (b) to explore pharmacological, relational and psychopathological factors related to this subjective response., Subjects and Methods: 78 subjects were rated (self rated response rate 61% (n = 48)) for (a) subjective response to neuroleptics, (b) compliance, (c) therapeutic alliance, (d) symptoms (e) severity of disorder., Results: Factor analysis yielded 2 main clinically relevant factors, similar to the original version: (I) global subjective response and (II) specific subjective response. Internal consistency is high. Correspondance analysis showed two important dimensions in the treatment of schizophrenic patients: (I) Recovery--aggravation, (II) Therapeutic ambition--positive or negative symptoms., Conclusion: French version of DAI-30 seems to have a similar structure and psychometric features as the original version. It shows concordance with the degree of compliance. Pharmacological factors are not the only factors implicated in subjective response, but are still to be identified. Limitations of our study are: (a) nonhomogenous indication for treatment, (b) small rate and degree of non compliance in our sample. Relationships between therapeutic ambition, type of symptoms and treatment outcome should be further studied.

We describe the case of a depressive patient who was a rapid metabolizer of CYP2D6 substrates and a heavy smoker, and who did not respond to several courses of treatment with antidepressants, as a result of unusually low drug-plasma levels. During hospitalization, he did not improve after treatment with clomipramine (150-225 mg/day during three weeks), but showed a response within four days after addition of fluvoxamine (100 mg/day). Plasma levels of clomipramine and desmethylclomipramine changed from 58 ng/ml and 87 ng/ml to 223 ng/ml and 49 ng/ml respectively one week after addition of fluvoxamine. Present knowledge of the role of cytochrome P-450 isozymes, such as CYP1A2, CYP2C19, CYP2D6, and CYP3A4, in the metabolism of psychotropic drugs as well as therapeutic drug-plasma level monitoring may thus help to determine individual treatment.

We investigated the relationship between the amount of ceftriaxone used in our hospital and the evolution of the rate of resistance among Enterobacter species isolates. We reviewed all positive microbiological reports for Enterobacter species and the pharmacy records for the ceftriaxone consumption during four semesters over 4 consecutive years. The resistance to ceftriaxone among Enterobacter species rose from 10 to 27% while the amount of ceftriaxone used almost trebled during the study period. In order to investigate the relationship between the use of an antibiotic and the emergence of resistance to it, we studied the development of ceftriaxone resistance in Enterobacter species and the use of this drug at the Centre Hospitalier Universitaire Vaudois (CHUV) each year between 1983 and 1986. The consumption of ceftriaxone more than doubled between 1983 and 1984, and since then has increased only slowly. Within 2 years the rate of Enterobacter species resistance to ceftriaxone has jumped from about 10% between 1983 and 1985 to 27% in 1986. As no particular modification in the preventive methods of hospital hygiene and no epidemics occurred during the period of our study, we conclude that the increase in the prescribing of ceftriaxone probably played a central role in the increased number of resistant strains of Enterobacter species.