Towards a pragmatic and operational definition of relapse in schizophrenia: A Delphi consensus approach.

OBJECTIVE: To develop pragmatic and operational definitions of relapse in schizophrenia. METHODS: A two-round Delphi consensus approach was used. The final questionnaire based on seven pre-established definition relapse models developed by a panel of eight experts was presented to 33 general psychiatrists who attended an "ad hoc" meeting. RESULTS: The most frequent components of the pragmatic definition were the psychopathological severity of the psychotic spectrum (70%), more intense management of the case (68%), a previously stabilized episode (67%), and impairment in functioning and social behavior (67%). In the operational definition, reappearance of symptoms was considered indispensable by 71% of the participants, and reappearance of positive symptoms measured by clinical scales was considered recommendable by 67%. Between 46% and 53% rated worsening of severity status and worsening of functioning as indispensable or recommendable. An increase of ≥ 10 points in the positive subscale of Positive and Negative Symptom Scale was rated by 51% of the participants, a score of 6 points in the Clinical Global Impression scale (much worse) by 89%, and a reduction of ≥ 20 points in the Global Assessment of Functioning scale by 62%. CONCLUSIONS: A better understanding of the definition of relapse in schizophrenia is necessary to improve effective prevention strategies.

Treatment adherence and quality of sleep in schizophrenia outpatients.

OBJECTIVE: Patients with schizophrenia (SZ) often present sleep complaints, and patients with sleep disturbances are at a greater risk for symptom worsening after antipsychotic discontinuation. Long-term adherence to antipsychotic treatment remains a challenge for clinicians, and the relationship between quality of sleep and treatment adherence in SZ outpatients has been poorly studied. METHODS: In this cross-sectional, non-interventional study, 811 adult outpatients with a diagnosis of SZ were divided into two groups according to the presence (or absence) of sleep disturbances, and assessed using measures of symptom severity, quality and patterns of sleep, adherence/compliance to treatment, and family support degree. RESULTS: Patients with sleep disturbances were significantly more symptomatic (p < 0.0001), and scored significantly higher on the Pittsburgh Sleep Quality Index (PSQI) as compared with patients without sleep disturbances (p < 0.0001). More compliant patients showed less sleep disturbances (p < 0.0001); moreover, patients with worse compliance to pharmacological treatment showed significantly higher scores on the PSQI (p < 0.0001). Regarding family support degree, patients with sleep disorders presented a lower family support (p = 0.0236), and patients with worse treatment adherence had worse family support (p < 0.0001). CONCLUSIONS: Our findings show that SZ outpatients reporting sleep disturbances show greater symptom severity, and worse adherence/compliance to treatment, as well as a lower family support.

Deciphering the Tangible Spatio-Temporal Spread of a 25-Year Tuberculosis Outbreak Boosted by Social Determinants.

Outbreak strains of Mycobacterium tuberculosis are promising candidates as targets in the search for intrinsic determinants of transmissibility, as they are responsible for many cases with sustained transmission; however, the use of low-resolution typing methods and restricted geographical investigations represent flaws in assessing the success of long-lived outbreak strains. We can now address the nature of outbreak strains by combining large genomic data sets and phylodynamic approaches. We retrospectively sequenced the whole genome of representative samples assigned to an outbreak circulating in the Canary Islands (the GC strain) since 1993, which accounts for ~20% of local tuberculosis cases. We selected a panel of specific single nucleotide polymorphism (SNP) markers for an in-silico search for additional outbreak-related sequences within publicly available tuberculosis genomic data. Using this information, we inferred the origin, spread, and epidemiological parameters of the GC strain. Our approach allowed us to accurately trace the historical and more recent dispersion of the GC strain. We provide evidence of a highly successful nature within the Canarian archipelago but limited expansion abroad. Estimation of epidemiological parameters from genomic data disagree with a distinctive biology of the GC strain. With the increasing availability of genomic data allowing for the accurate inference of strain spread and critical epidemiological parameters, we can now revisit the link between Mycobacterium tuberculosis genotypes and transmission, as is routinely carried out for SARS-CoV-2 variants of concern. We demonstrate that social determinants rather than intrinsically higher bacterial transmissibility better explain the success of the GC strain. Importantly, our approach can be used to trace and characterize strains of interest worldwide. IMPORTANCE Infectious disease outbreaks represent a significant problem for public health. Tracing outbreak expansion and understanding the main factors behind emergence and persistence remain critical to effective disease control. Our study allows researchers and public health authorities to use Whole-Genome Sequencing-based methods to trace outbreaks, and shows how available epidemiological information helps to evaluate the factors underpinning outbreak persistence. Taking advantage of all the freely available information placed in public repositories, researchers can accurately establish the expansion of an outbreak beyond original boundaries, and determine the potential risk of a strain to inform health authorities which, in turn, can define target strategies to mitigate expansion and persistence. Finally, we show the need to evaluate strain transmissibility in different geographic contexts to unequivocally associate spread to local or pathogenic factors, an important lesson taken from genomic surveillance of SARS-CoV-2.

Rapid test for identification of a highly transmissible Mycobacterium tuberculosis Beijing strain of sub-Saharan origin.

The development of a rapid test to identify Mycobacterium tuberculosis Beijing isolates and specifically strain GC1237, coming from a sub-Saharan country, is needed due to its alarming wide spread on Gran Canaria Island (Spain). A rapid test that detects IS6110 present between dnaA and dnaN in the Beijing strains and in a specific site for GC1237 (Rv2180c) has been developed. This test would be a useful tool in the surveillance of subsequent cases.

Adherence to treatment and therapeutic strategies in schizophrenic patients: the ADHERE study.

AIM: To assess the degree of compliance and adherence to treatment during the follow-up of schizophrenic outpatients after a new therapeutic strategy had been initiated. METHODS: A multicenter, retrospective, prospective, observational study of 1,848 outpatients with schizophrenia or schizoaffective disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was conducted. Patients were treated either with oral or injectable conventional or second generation antipsychotics, and were followed up for 3 months at mental health centers. Patient compliance with the pharmacological treatment was assessed by the use of questionnaires, scales, medication accountability, and the Medication Event Monitoring System. Patients were considered compliant if they reported a high compliance rate (> or = 80%). RESULTS: At baseline only 29% of patients on oral medication were compliant compared with 79% of patients on injectable medication (injection counting) (OR= 9.11; 95% CI 6.02-13.77; P<.0001). At the 3 month visit, 84% of patients had changed their treatment and in these, the compliance rate of those on injectable medication was 94% versus 87% of patients taking oral medication (OR= 2.47; 95% CI 1.21-5.05; P=.022). CONCLUSION: The use of long-acting injectable antipsychotics, which improves compliance rates and patient follow-up, should facilitate the management of Spanish patients with schizophrenia in mental health centers.

A Mycobacterium tuberculosis Beijing strain persists at high rates and extends its geographic boundaries 20 years after importation.

Transmission of Beijing Mycobacterium tuberculosis can be investigated based on genotypic analysis of clinical isolates. A Beijing strain began to spread on Gran Canaria Island, Spain, at the end of the last century. In 1996, only 3 years after its importation to the island, its frequency had increased to 27.1% of all the isolates. The strain was tracked during the following years, and the most recent data obtained corresponded to 2007-8, when its presence continued to be alarming (21%). In the current study, we updated data on the distribution of this strain 20 years (2013-2014) after it was first detected on the island and extended the analysis for the first time to all the mycobacteriology laboratories covering the population of the Canary Island archipelago. Rapid updating was enabled by means of 2 different strain-specific PCRs: one targeting a peculiar feature of the strain, which was identified based on an IS6110 copy mapping in the Rv2180c gene, and a newly defined strain-specific single nucleotide polymorphism, which was identified by whole-genome sequencing. The results showed that the strain has remained highly prevalent (20.90% of all isolates), has spread throughout the neighbouring islands, and has also reached high representativeness in them (11-32%).

Long-acting injectable antipsychotics for the treatment of schizophrenia in Spain. / Antipsicóticos inyectables de liberación prolongada para el tratamiento de la esquizofrenia en España.

Antipsychotics are an essential component in the treatment of schizophrenia. Long-acting injectable formulations (LAI) arose to improve adherence with the associated potential of reducing the risk of relapse. The objective of this article is to analyze the use of LAI antipsychotics in Spain, which is similar to other European countries but with a predominance of the use of second generation LAI, to discuss the possible causes of prescribing differences with respect to other countries (including organizational aspects, attitudes of psychiatrists, patients and family members, and clinical practice guidelines), and to discuss their use in acute psychiatric units, first episode, and in children and adolescents. In our view, while it is necessary to increase existing evidence regarding the advantages of LAI antipsychotics and the differentiation between LAI antipsychotics currently available, their use will likely continue to grow driven by clinical experience.

A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Hydroxide Ions Stabilize Open Carbon Nanotubes in Degassed Water.

The main hurdle preventing the widespread use of single-walled carbon nanotubes remains the lack of methods with which to produce formulations of pristine, unshortened, unfunctionalized, individualized single-walled carbon nanotubes, thus preserving their extraordinary properties. In particular, sonication leads to shortening, which is detrimental to percolation properties (electrical, thermal, mechanical, etc.). Using reductive dissolution and transfer into degassed water, open-ended, water-filled nanotubes can be dispersed as individualized nanotubes in water-dimethyl sulfoxide mixtures, avoiding the use of sonication and surfactant. Closed nanotubes, however, aggregate immediately upon contact with water. Photoluminescence and absorption spectroscopy both point out a very high degree of individualization while retaining lengths of several microns. The resulting transparent conducting films are 1 order of magnitude more conductive than surfactant-based blanks at equal transmittance.

Management of agitation in the acute psychotic patient--efficacy without excessive sedation.

Rapid-acting intramuscular (IM) formulations of atypical antipsychotics offer a significant advance over IM haloperidol in the short-term management of acute schizophrenic episodes. Several short-term open-label randomised studies, typically enrolling two- to three-hundred patients, have compared an atypical antipsychotic with haloperidol. These studies show that IM ziprasidone, IM olanzapine and IM aripiprazole are at least as effective and better tolerated than IM haloperidol, with lower extrapyramidal side effects. Successful transitions from an IM to oral formulation of the same agent have been performed in double-blind randomised trials assessing haloperidol, olanzapine, ziprasidone and aripiprazole. Avoiding over-sedation is now recognised as important, and randomised clinical trial data indicate that oral ziprasone, quetiapine, and IM olanzapine have high dose-related sedative potential while oral risperidone and IM aripiprazole have low sedative potential. In summary, IM formulations of atypical antipsychotics are recommended as first-line treatment of acute agitation with subsequent transition to an oral formulation of the same agent for ongoing management.

Cost-effectiveness analysis of ziprasidone versus haloperidol in sequential intramuscular/oral treatment of exacerbation of schizophrenia: economic subanalysis of the ZIMO trial.

OBJECTIVE: This study aimed to assess the cost effectiveness of ziprasidone versus haloperidol in sequential intramuscular (IM)/oral treatment of patients with exacerbation of schizophrenia in Spain. METHODS: A cost-effectiveness analysis from the hospital perspective was performed. Length of stay, study medication and use of concomitant drugs were calculated using data from the ZIMO trial. The effectiveness of treatment was determined by the percentage of responders (reduction in baseline Brief Psychiatric Rating Scale [BPRS] negative symptoms subscale >or=30%). Economic assessment included estimation of mean (95% CI) total costs, cost per responder and the incremental cost-effectiveness ratio (ICER) per additional responder. The economic uncertainty level was controlled by resampling and calculation of cost-effectiveness acceptability curves. RESULTS: A total of 325 patients (ziprasidone n = 255, haloperidol n = 70) were included in this economic subanalysis. Ziprasidone showed a significantly higher responder rate compared with haloperidol (71% vs 56%, respectively; p = 0.023). Mean total costs were euro3582 (95% CI 3226, 3937) for ziprasidone and euro2953 (95% CI 2471, 3436) for haloperidol (p = 0.039), mainly due to a higher ziprasidone acquisition cost. However, costs per responder were lower with ziprasidone (euro5045 [95% CI 4211, 6020]) than with haloperidol (euro5302 [95% CI 3666, 7791], with a cost per additional responder (ICER) for ziprasidone of euro4095 (95% CI -130, 22 231). The acceptability curve showed an ICER cut-off value of euro13 891 at the 95% cost-effectiveness probability level for >or=30% reduction in BPRS negative symptoms. CONCLUSIONS: Compared with haloperidol, ziprasidone was significantly better at controlling psychotic negative symptoms in acute psychoses. The extra cost of ziprasidone was offset by a higher effectiveness rate, yielding a lower cost per responder. In light of the social benefit (less family burden and greater restoration of productivity), the incremental cost per additional responder with sequential IM/oral ziprasidone should be considered cost effective in patients with exacerbation of schizophrenia in Spain.

Adherence predicts symptomatic and psychosocial remission in schizophrenia: Naturalistic study of patient integration in the community. / La adherencia predice la remisión sintomática y psicosocial en esquizofrenia: estudio naturalístico de la integración de los pacientes en la comunidad.

INTRODUCTION: Psychosocial functioning in patients with schizophrenia attended in daily practice is an understudied aspect. The aim of this study was to assess the relationship between symptomatic and psychosocial remission and adherence to treatment in schizophrenia. METHODS: This cross-sectional, non-interventional, and multicenter study assessed symptomatic and psychosocial remission and community integration of 1,787 outpatients with schizophrenia attended in Spanish mental health services. Adherence to antipsychotic medication in the previous year was categorized as≥80% vs.<80%. RESULTS: Symptomatic remission was achieved in 28.5% of patients, and psychosocial remission in 26.1%. A total of 60.5% of patients were classified as adherent to antipsychotic treatment and 41% as adherent to non-pharmacological treatment. During the index visit, treatment was changed in 28.4% of patients, in 31.1% of them because of low adherence (8.8% of the total population). Adherent patients showed higher percentages of symptomatic and psychosocial remission than non-adherent patients (30.5 vs. 25.4%, P<.05; and 32 vs. 17%, P<.001, respectively). Only 3.5% of the patients showed an adequate level of community integration, which was also higher among adherent patients (73.0 vs. 60.1%, P<.05). CONCLUSIONS: Adherence to antipsychotic medication was associated with symptomatic and psychosocial remission as well as with community integration.

Safety and effectiveness of olanzapine in monotherapy: a multivariate analysis of a naturalistic study.

BACKGROUND: This study investigated safety and effectiveness of olanzapine in monotherapy compared with conventional antipsychotics in treatment of acute inpatients with schizophrenia. METHOD: This was a prospective, comparative, nonrandomized, open-label, multisite, observational study of Spanish inpatients with an acute episode of schizophrenia. Data included safety assessments with an extrapyramidal symptoms (EPS) questionnaire and the report of spontaneous adverse events, plus clinical assessments with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate methodology was used to more adequately determine which factors can influence safety and effectiveness of olanzapine in monotherapy. RESULTS: 339 patients treated with olanzapine in monotherapy (OGm) and 385 patients treated with conventional antipsychotics (CG) were included in the analysis. Treatment-emergent EPS were significantly higher in the CG (p<0.0001). Response rate was significantly higher in the OGm (p=0.005). Logistic regression analyses revealed that the only variable significantly correlated with treatment-emergent EPS and clinical response was treatment strategy, with patients in OGm having 1.5 times the probability of obtaining a clinical response and patients in CG having 5 times the risk of developing EPS. CONCLUSION: In this naturalistic study olanzapine in monotherapy was better-tolerated and at least as effective as conventional antipsychotics.

Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia: a multivariate analysis of a large naturalistic study in the hospital setting.

BACKGROUND AND OBJECTIVE: This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness. PATIENTS AND METHOD: This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients' entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed. RESULTS: Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007). CONCLUSIONS: Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.

Nurses' perceptions of medication adherence in schizophrenia: results of the ADHES cross-sectional questionnaire survey.

OBJECTIVES: Poor adherence to antipsychotic treatment is a widespread problem within schizophrenia therapy with serious consequences including increased risks of relapse and rehospitalization. Mounting evidence supports the key roles that nurses play in monitoring patient progress and facilitating long-term treatment adherence. The Adherencia Terapéutica en la Esquizofrenia (ADHES) nurses' survey was designed to assess the opinions of nurses on the causes and management of partial/nonadherence to antipsychotic medication. METHODS: A questionnaire-based cross-sectional survey of 4120 nurses from Europe, the Middle East and Africa. Interpretation of results was based on a descriptive comparison of responses. RESULTS: Nurses perceived 54% of patients seen in the preceding month to be partially/nonadherent to treatment. Most nurses (90%) reported some level of experience with administration of long-acting injectable (LAI) antipsychotics, with 24% of nurses administering >10 injections per month. The majority (85%) of nurses surveyed believed that improving adherence would improve patient outcomes. Nearly half (49%) reported that most of their patients depend on a family member or other nonprofessional carer to remind them to take their medication as prescribed. A similar proportion of nurses (43%) reported that most of their patients relied on a professional to remind them to take medication. Most nurses (92%) felt that ensuring continuous medication with LAI antipsychotics would yield long-term benefits for patients, but their opinion was that over a third of patients were unaware of LAI antipsychotic treatments. In a series of forced options, the strategy used most often by respondents (89%) to promote medication adherence was to build trusting relationships with patients while listening to and interpreting their needs and concerns. Respondents also rated this as the most effective strategy that they used (48%). CONCLUSION: Nurses are highly aware of adherence issues faced by their patients; further patient education on treatment options is needed.

Resistance to first-line antituberculosis drugs in Spain, 2010-2011. RETUBES Study.

INTRODUCTION: The magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. METHODS: Prospective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. RESULTS: A total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR=2.3; 95%CI: .98-5.67 and OR=2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03). CONCLUSIONS: The rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.

Rafts: a simple way to control apoptosis by subcellular redistribution.

Apoptosis is an essential feature of development and homeostasis in higher organisms. Lipid rafts are subdomains of the plasma membrane that contain high concentrations of cholesterol and sphingolipids. In response to intra or extracellular stimuli, lipid rafts can include or exclude proteins to variable extents. This favors specific protein-protein interactions and modulates the activity of signaling cascades. Recently, a number of proteins involved in apoptotic signals have been located in lipid rafts. Among these proteins is included Bad, a pro-apoptotic molecule belonging to the Bcl-2 family. Bad is attached to lipid rafts in proliferating cells while associated to mitochondria in apoptotic cells, suggesting that the interaction of Bad with rafts is a dynamic process involved in the control of apoptosis. In this review, we briefly summarize the structure of rafts and illustrate their contribution to the control of apoptosis.

Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

Safety and effectiveness of olanzapine versus conventional antipsychotics in the acute treatment of first-episode schizophrenic inpatients.

OBJECTIVE: To assess the safety and effectiveness of olanzapine compared to typical antipsychotics in the treatment of first-episode schizophrenics in acute psychiatric inpatient wards. METHODS: Data were collected from a prospective, comparative, nonrandomized, open, observational study of 904 inpatients with schizophrenia. One hundred and fifty-eight patients fulfilled the criteria for first-episode schizophrenia, defined as (1) the International Classification of Diseases: Mental and Behavioral Disorders, 10th ed. (ICD-10) diagnosis of schizophrenia, (2) antipsychotic nai;ve, and (3) a course of illness of less than 5 years. Eighty-nine (56.3%) of these patients were assigned to the olanzapine treatment group (OLZ) and 69 (43.7%) to the control group that received treatment with conventional antipsychotics (CON). Safety was evaluated in terms of the spontaneous adverse events reported and a specific questionnaire for extrapyramidal symptoms (EPS). Clinical status was measured by means of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Severity (CGI-S). Clinical response was defined as the baseline-endpoint decrease in BPRS>40% plus an endpoint BPRS<18 or an endpoint CGI

Safety of olanzapine versus conventional antipsychotics in the treatment of patients with acute schizophrenia. A naturalistic study.

BACKGROUND: Conventional antipsychotics although effective in treating acute psychotic and behavioural symptoms are subject to certain limitations due to the high incidence of side effects associated, mainly extrapyramidal symptoms (EPS), and insufficient response shown in some cases. EPS are a major factor in neuroleptic non compliance and high relapse rates among patients. This study was designed to assess the safety and effectiveness of olanzapine compared to typical antipsychotics drugs in the treatment of schizophrenic inpatients at acute psychiatric in-patient units. METHOD: Data from 904 patients schizophrenic patients (F20 of ICD10, WHO) were collected in this prospective, comparative, non-randomized, open and observational study. Patients were followed during their entire hospital stay. Safety was assessed through the collection of spontaneous adverse events and a specific extrapyramidal symptoms questionnaire (EPS). Clinical status was measured through the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Improvement (PGI) and the Nursing Observational Scale for In-patient Evaluation (NOSIE). RESULTS: A total of 483 patients received olanzapine (olanzapine group, OG), and 421 received typical antipsychotics (control group, CG). Treatment emergent EPS, or worsening of previous EPS were statistically significantly higher in the CG (P=0.001). Responder rate was statistically greater in the OG (P<0.001). Mean change in BPRS-total, BPRS-negative, BPRS-agitation subscales and PGI was significantly higher in the OG (P<0.001). Mean decrease in CGI, BPRS positive and BPRS depression sub-scales was also significantly lower (P< or =0.05). Mean change in the NOSIE scale was similar between both groups. CONCLUSION: Olanzapine has been shown to be better tolerated in comparison with conventional antipsychotics in a large unselected sample of acutely psychotic schizophrenic in-patients. Its effectiveness may be greater than that of conventional antipsychotics.