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Although continuous treatment with antipsychotics is still recommended as the gold standard treatment paradigm for all patients with schizophrenia, some clinicians question whether continuous antipsychotic treatment is necessary, or even justified, for every patient with schizophrenia who has been stabilized on antipsychotics. The primary objectives of this systematic review and meta-analysis were (i) to compare relapse/hospitalization risks of stabilized patients with schizophrenia under active versus intermittent or placebo treatment conditions; (ii) to examine the role of several study characteristics, possibly intervening in the relationship between relapse risk and treatment condition; and (iii) to examine whether time to relapse is associated with antipsychotic treatment duration. A systematic literature search, using the MEDLINE database (1950 until November 2014), was conducted for English-language published randomized controlled trials, covering a follow-up time period of at least 6 months, and investigating relapse/rehospitalization and/or time-to-relapse rates with placebo or intermittent treatment strategies versus continuous treatment with oral and long-acting injectable first- or second-generation antipsychotics (FGAs/SGAs) in stabilized patients with schizophrenia. Additional studies were identified through searches of reference lists of other identified systematic reviews and Cochrane reports. Two meta-analyses (placebo versus continuous and intermittent versus continuous treatment) were performed to obtain an optimal estimation of the relapse/hospitalization risks of stabilized patients with schizophrenia under these treatment conditions and to assess the role of study characteristics. For time-to-relapse data, a descriptive analysis was performed. Forty-eight reports were selected as potentially eligible for our meta-analysis. Of these, 21 met the inclusion criteria. Twenty-five records, identified through Cochrane and other systematic reviews and fulfilling the inclusion criteria, were added, resulting in a total of 46 records. Stabilized patients with schizophrenia who have been exposed for at least 6 months to intermittent or placebo strategies, respectively, have a 3 (odds ratio [OR] 3.36; 95 % CI 2.36–5.45; p

Objective: This study was designed to explore the efficacy and tolerability of oral paliperidone extended release (ER) in a sample of patients who were switched to flexible doses within the crucial first 5 years after receiving a diagnosis of schizophrenia. Methods: Patients were recruited from 23 countries. Adults with nonacute but symptomatic schizophrenia, previously unsuccessfully treated with other oral antipsychotics, were transitioned to paliperidone ER (3–12 mg/day) and prospectively treated for up to 6 months. The primary efficacy outcome for patients switching for the main reason of lack of efficacy with their previous antipsychotic was at least 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores. For patients switching for other main reasons, such as lack of tolerability, compliance or ‘other’, the primary outcome was non-inferiority in efficacy compared with the previous oral antipsychotic. Results: For patients switching for the main reason of lack of efficacy, 63.1% achieved an improvement of at least 20% in PANSS total scores from baseline to endpoint. For each reason for switching other than lack of efficacy, efficacy maintenance after switching to paliperidone ER was confirmed. Statistically significant improvement in patient functioning from baseline to endpoint, as assessed by the Personal and Social Performance scale, was observed ( p < 0.0001). Treatment satisfaction with prior antipsychotic treatment at baseline was rated ‘good’ to ‘very good’ by 16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone ER. Paliperidone ER was generally well tolerated, with frequently reported treatment-emergent adverse events being insomnia, anxiety and somnolence. Conclusions: Flexibly dosed paliperidone ER was associated with clinically relevant symptomatic and functional improvement in recently diagnosed patients with non-acute schizophrenia previously unsuccessfully treated with other oral antipsychotics.

Aims: Assessment of oral paliperidone ER therapy. Methods: A subgroup analysis of patients with schizophrenia switched from unsuccessful oral risperidone therapy in a 6-month, open-label, multicenter study investigating flexibly dosed paliperidone ER. Results: 694 patients were analyzed (59.2% male; mean age: 40.0 years). Mean change in PANSS total score from baseline to end point was -14.4 ± 20.2 in patients switching due to lack of efficacy (n = 359). Mean change in PANSS total score for patients switching for other reasons (n = 319) was: -7.6 ± 17.0 (lack of tolerability, n = 175), -19.6 ± 20.3 (lack of compliance, n = 76), and -12.0 ± 16.8 (other, n = 68). Conclusion: In patients with schizophrenia previously unsuccessfully treated with oral risperidone, paliperidone ER was well tolerated and associated with a meaningful treatment response.

The European First Episode Schizophrenia Trial (EUFEST) included first-episode schizophrenia patients, assessing the efficacy of five antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine and ziprasidone) over one year. Baseline frequency of extrapyramidal symptoms (EPS) in this group of patients (n=490) was as follows: parkinsonism 10.8%, akathisia 10.0%, dystonia 1.8%, and dyskinesia 0.6%. The frequency of parkinsonism at baseline was greater in patients with a brief prior exposure to antipsychotics (≤2 weeks) compared with antipsychotic-naïve ones, and was positively correlated with the intensity of negative symptoms and negatively with depressive symptoms. After one month of treatment, the increase of parkinsonism was highest in patients receiving haloperidol (+13%), that of akathisia in patients treated with ziprasidone (+14%), and 10.1% of the patients were taking anticholinergic drugs, most frequently in the haloperidol group (24%). In 291 patients remaining on treatment after one year, both parkinsonism and akathisia had decreased: the frequency of parkinsonism was 3%, highest in the haloperidol group (9.1%), that of akathisia was 3%, highest in the quetiapine group (7.5%), and 4% of patients were taking anticholinergic drugs, most frequently those receiving haloperidol (10.5%). The results obtained suggest that in first-episode schizophrenia patients during the first year of antipsychotic treatment (in this case amisulpride, haloperidol in low doses, olanzapine, quetiapine and ziprasidone), EPS were present as manageable clinical problems.

Using antipsychotic (AP) medication can increase prolactin (PRL) levels and place the patient at risk of sexual dysfunction (SD).The aim of this review is to describe the PRL propensity of the different second-generation and newly approved APs. It then considers the prevalence rates of SDs associated with these compounds in patients with schizophrenia and treatment strategies for the management of SDs and/or hyperprolactinemia (HPRL). Furthermore, we address the lingering question regarding the association between SDs and PRL.SD (particularly long-term) data remain scarce for several APs. A wide variety of assessment techniques used in SD research make reliable comparisons between APs impossible. The majority of these reports do not equally allow us to distinguish between treatment (AP and co-medication)-emergent SDs and illness-related SDs. This makes it difficult to assess the degree to which these side effects are associated with 'PRL-raising' APs, and what part of this fraction is directly reducible to serum PRL levels. Also, few evidence-based treatment strategies for HPRL and associated side effects are available. Therefore, longer-term randomized controlled trials, using reliable and valid structured interviews or questionnaires, are necessary to establish the precise relationship between APs, PRL levels and SDs rates and develop valuable treatment options.

Objectives: Antipsychotic drug side effects are common and can cause stigmatisation, decreased quality of life, poor adherence, and secondary morbidity and mortality. Systematic assessment of anticipated side effects is recommended as part of good clinical care, but is uncommon in practice and patients may not spontaneously report side effects. We aimed to develop a simple patient-completed checklist to screen systematically for potential antipsychotic side effects. Methods: The SMARTS checklist was developed over a series of group meetings by an international faculty of 12 experts (including psychiatrists, a general physician and a psychopharmacologist) based on their clinical experience and knowledge of the literature. The emphasis is on tolerability (i.e. assessment of side effects that ‘trouble’ the patient) as subjective impact of side effects is most relevant to medication adherence. The development took account of feedback from practising psychiatrists in Europe, the Middle East and Africa, a process that contributed to face validity. Results: The SMARTS checklist assesses whether patients are currently ‘troubled’ by 11 well-established potential antipsychotic side effects. Patients provide their responses to these questions by circling relevant side effects. An additional open question enquires about any other possible side effects. The checklist has been translated into Italian and Turkish. Conclusions: The SMARTS checklist aims to strike a balance between brevity and capturing the most common and important antipsychotic side effects. It is appropriate for completion by patients prior to a clinical consultation, for example, in the waiting room. It can then form the focus for a more detailed clinical discussion about side effects. It can be used alone or form part of a more comprehensive assessment of antipsychotic side effects including blood tests and a physical examination when appropriate. The checklist assesses current problems and can be used longitudinally to assess change.

Aim: Potential differences in psychiatric clinical outcomes and hospitalization rates before and after the initiation of long-acting risperidone among recently and long-term diagnosed schizophrenia patients were studied. Methods: Data from two observational studies (Trial for the Initiation and Maintenance Of REmission in Schizophrenia with risperidone (TIMORES) and electronic Schizophrenia Treatment Adherence Registry (e-STAR)) were categorized by the recency of their diagnose and compared in several post hoc analyses. Clinical Global Impression of illness Severity (CGI-S) and Global Assessment of Functioning (GAF) scores, as well as symptoms of clinical deterioration (including hospitalization data) at baseline, 12-month (for TIMORES and e-STAR) and 24-month (for e-STAR) follow-up were analysed. Other outcome measures included discontinuation rate, employment status and remission attainment. Results: Statistically significantly differences between recent and long-term diagnosed schizophrenic patients at 12- and 24-month follow-up were found for CGI-S (between P

Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the “at-risk mental state.” Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P

Background Cannabis use may decrease age at onset in both schizophrenia and bipolar disorder, given the evidence for substantial phenotypic and genetic overlap between both disorders. Methods 766 patients, aged 16 to 65 years, were assessed with the Composite International Diagnostic Interview (CIDI) for substance abuse/use. 676 subjects were diagnosed with schizophrenia and 90 subjects with bipolar disorder. The influence of cannabis use on age at onset in both schizophrenia and bipolar disorder was examined using regression analysis. Results Cannabis and other substance use was more frequent in patients with schizophrenia compared to the bipolar group. Both cannabis use and a schizophrenia diagnosis predicted earlier age at onset. There was a significant interaction between cannabis use and diagnosis, cannabis having a greater effect in bipolar patients. Age at onset in users of cannabis was comparable in both diagnostic groups whereas bipolar non-users were significantly older than schizophrenia non-users at onset. Conclusion Cannabis use may decrease age at onset in both schizophrenia and bipolar patients and reduce the effect of diagnosis. This is consistent with the view that cannabis use may unmask a pre-existing genetic liability that is partly shared between patients with schizophrenia and bipolar disorder.

Antipsychotics are the cornerstone in the management of psychotic disorders and schizophrenia. They are effective agents but also have a wide range of side effects. In the recent literature constipation as possible side effect has received little attention. A review of the literature concerning constipation associated with antipsychotics was performed. Overall constipation is a rarely studied or reported side effect of antipsychotic medication. Nevertheless constipation is a common side effect. Antipsychotic agents differ in their liability to induce constipation. Constipation can be severe and can lead to serious consequences such as paralytic ileus, bowel occlusion and death. Active screening, monitoring and treatment are recommended. Further research on incidence, prevalence, underlying mechanisms and preventive measures is required.

Context In the healthy population, several pathways are known to exert an effect on basal metabolic factors. Previous studies have found associations between single nucleotide polymorphisms in clock genes or downstream hormone receptors such as the leptin receptor (LEPR) or glucocorticoid receptor (NR3C1) and obesity in the healthy population, but this association remains to be examined in patients with schizophrenia treated with antipsychotics. Objective To assess anthropomorphic parameters in patients taking second-generation antipsychotics (SGA) as a function of nine polymorphisms in three core genes of the clock pathway, and two genes of downstream hormone receptors. Methods Clinical parameters were evaluated in 261 patients with schizophrenia spectrum disorder. Polymorphisms in LEPR, MC3R, NR3C1, PER2 and SDC3 were genotyped. In order to control for multiple testing, permutation tests were used to generate corrected empirical p-values using the Max ( T ) procedure in PLINK. Results A significant effect of the rs6196 polymorphism in the NR3C1 on weight (β = −4.18; SE = 2.02; p = 0.018), BMI (β = −1.88; SE = 0.64; p = 0.004), waist (β = −5.77; SE = 1.75; p = 0.001) and waist/hip ratio (β = −0.03; SE = 0.012; p = 0.009) was found. Permutation tests confirmed the findings for BMI (p = 0.037) and waist (p = 0.024). Carriers of the G allele consistently displayed better parameters than patients with the wild type allele. A weak effect of rs4949184 in SDC3 on BMI was found, but this did not sustain permutation testing (β = −1.27; SE = 0.58; p = 0.030, p = 0.270 after permutations). Conclusion Variations in genes implicated in circadian regulation or its related downstream pathways may be important in the regulation of antropomorphic parameters in patients with schizophrenia during long-term treatment with SGA.

The incidence of suicide attempts (fatal and non-fatal) was analysed in a prospective cohort of patients with schizophrenia randomly assigned to sertindole (4905 patients) or risperidone (4904 patients) in a parallel-group open-label study with blinded classification of outcomes (the sertindole cohort prospective study--SCoP). The total exposure was 6978 and 7975 patient-years in the sertindole and risperidone groups, respectively. Suicide mortality in the study was low (0.21 and 0.28 per 100 patients per year with sertindole and risperidone, respectively). The majority (84%) of suicide attempts occurred within the first year of treatment. Cox's proportional hazards model analysis of the time to the first suicide attempt, reported by treating psychiatrists and blindly reviewed by an independent expert group according to the Columbia Classification Algorithm of Suicide Assessment (both defining suicide attempts by association of suicidal act and intent to die), showed a lower risk of suicide attempt for sertindole-treated patients than for risperidone-treated patients. The effect was statistically significant with both evaluation methods during the first year of randomized treatment (hazard ratios [95% CI]: 0.5 [0.31-0.82], p=0.006; and 0.57 [0.35-0.92], p=0.02, respectively). With classification by an independent safety committee using a broader definition including all incidences of intentional self-harm, also those without clear suicidal intent, the results were not significant. A history of previous suicide attempts was significantly associated with attempted suicides in both treatment groups.

Cognition has been studied extensively in schizophrenia in Western countries. Far less research is devoted, however, to cognitive functioning in brief psychotic disorder and schizophreniform disorder. Moreover, few studies have been performed in third world countries. In this study, we want to fill this gap by comparing the cognitive functioning of three groups of ambulant, first-episode patients with a non-affective psychosis in the Democratic Republic of Congo. To test if cognitive dysfunction is a core symptom of psychosis in an African population, 153 healthy control subjects are compared with a sample of 68 patients with brief psychotic disorder, 50 patients with schizophreniform disorder, and 70 patients with schizophrenia in a cross-sectional study on several distinctive cognitive domains including verbal, visual, and working memory, attention, visuomotor control, motor speed, verbal fluency, and executive functions. In addition, these three groups of patients are compared among themselves on these cognitive domains. Results indicate that patients perform significantly worse than healthy controls on all cognitive domains with cognitive deficits being most pronounced in verbal and working memory, attention, motor speed, and executive functions. No major differences were found, however, between the three patient groups.

The presence of the metabolic syndrome is an important risk factor for cardiovascular disease and diabetes. The short- and long-term metabolic safety of sertindole was compared to that of risperidone in a subset of patients enrolled in the sertindole cohort prospective (SCoP) study, an open randomized study. In 261 randomized patients, there were moderate increases in mean weight, BMI, and waist circumference during treatment with either sertindole or risperidone; after 12 weeks, the increase in weight was 1.3 and 1.1 kg, respectively, and after 36 weeks, it was 2.2 and 2.0 kg, respectively. From baseline to last assessment (up to 60 weeks), weight gains of 1.8 and 1.7 kg for sertindole and risperidone, respectively, were observed. Similar proportions of patients (sertindole: 17% versus risperidone: 16%) had weight increases ≥7% from baseline to last assessment. The mean changes from baseline in triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small and not clinically relevant in both treatment groups. No patient in either of the groups developed type 2 diabetes during the study. At last assessment, the prevalence of metabolic syndrome (International Diabetes Federation) was 17% in the sertindole group and 26% in the risperidone group and the incidence of metabolic syndrome was 7% in the sertindole group and 10% in the risperidone group. Treatment with either sertindole or risperidone did not appear to be associated with an increased comparative risk of developing metabolic syndrome. In general, the metabolic effects of sertindole and risperidone were similar.

Summary Background: Physical restraint and seclusion are associated with several risks. Antipsychotic drug use increases this risk. Objective: To evaluate whether the risk of thromboembolism in physical restraint and seclusion of patients with psychosis, treated with antipsychotic medication, was considered by taking preventive measures. Method: Anonymous data on all consecutively admitted patients with schizophrenia, treated with antipsychotic medication, between 2002 and 2009, were analysed. Diagnostic information and data about seclusion procedures and medication were collected. Preventive measures of thromboembolism in patients in physical restraint were assessed by reviewing case notes and the medication prescribed at the time of seclusion. Results: Seclusion of patients with psychosis is common. Out of 679 identified patients, 170 had been secluded (472 events). Physical restraint use was not a rare event (N seclusions with restraint use 296, 62.7%). Pharmacological preventive measures (use of heparine dugs) were taken frequently to prevent deep vein thrombosis (DVT) by physical restraint or isolation. Sixty-five (38.2%) out of 170 secluded patients, including a majority of patients who had been under physical restraint, had been administered anticoagulants at the time of seclusion. No cases of DVT occurred. Conclusions: Preventive measures were routinely administered in clinical practice and were effective in the prevention of DVT. For a clinical setting, it is important to establish a clear and detailed management plan on seclusion and fixation taken into account in all possible risks of physical restraint.

This article reviews evidence that researchers and mental health service providers need to take into account four modifiable factors that affect the prevalence of the metabolic syndrome in people with schizophrenia: (a) physical activity as part of a health-related lifestyle, (b) physical fitness, (c) mental health status and (d) antipsychotic medication. The implementation of physical activity in order to prevent and treat cardiometabolic risk factors in people with schizophrenia is discussed. English language articles published until July 2009 were identified by PubMed, CINAHL, PsychINFO, and Cochrane Central Register of Controlled Trials. The search terms schizophrenia and metabolic syndrome, physical activity, health, fitness, and lifestyle were used. Physical activity interventions result in positive effects on metabolic outcomes, physical fitness, health-related behavior and mental health. Considering present knowledge, physical therapists should take into account the emotional (negative symptoms, self-esteem, self-efficacy, and stress) and physiological (cardiometabolic parameters) components of mental illness when offering physical activity interventions. The physical activity stimulus should be adapted to the individual's physical fitness level and the side effects of the antipsychotic medications. More research is needed to assist in the practical development of effective evidence-based preventive and curative strategies in psychiatric services for metabolic syndrome in persons with schizophrenia.

Despite available effective medications, many patients with schizophrenia do not become completely symptom free. We report analyses of data from a randomized, double-blind, placebo-controlled relapse prevention study of extended release quetiapine fumarate (quetiapine XR) using Remission in Schizophrenia Working Group criteria for symptomatic remission. During 16-week open-label stabilization, patients with stable schizophrenia were switched from their current antipsychotic to quetiapine XR (400, 600 or 800 mg/day flexibly dosed). One hundred and ninety-seven patients were randomized to either quetiapine XR or placebo (planned for 1 year or until relapse). The study was terminated early because the planned interim analysis showed quetiapine XR to be statistically superior to placebo in the primary outcome variable (time to schizophrenia relapse). One hundred and eighty of 195 (92.3%) patients with an available Positive and Negative Syndrome Scale assessment met symptomatic remission criteria at randomization (following 16 weeks' quetiapine XR). The risk of losing symptomatic remission was statistically significantly higher with placebo versus quetiapine XR: hazard ratio 0.39 (95% confidence interval: 0.19-0.81, P=0.009), that is, 61% risk reduction for quetiapine XR-treated versus placebo-treated patients. At 6 months postrandomization, the probability that patients would be in remission was 76% for quetiapine XR and 52% for placebo. Once-daily quetiapine XR was effective in preserving symptomatic remission in the longer-term treatment of patients with schizophrenia.

Thomas SHL, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghoj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP) Objective: To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. Method: Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. Results: After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). Conclusion: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.

To assess treatment retention on risperidone long-acting injection (RLAI) and outcomes in schizophrenia patients for whom 24 months of follow-up data in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) were available.e-STAR is an ongoing, international, multicenter, prospective, observational registry assessing use of antipsychotics in patients with schizophrenia or schizoaffective disorder in a normal clinical practice setting. Parameters were assessed prior to and post-initiation of RLAI. Data presented are from six European countries that enrolled patients in e-STAR after they initiated treatment with RLAI.Clinical and demographic information were collected at baseline and treatment-related data, including RLAI discontinuation, psychiatric hospitalization and medication utilization, were collected prospectively every 3 months. Data collection continued for 24 months, even for patients who discontinued RLAI therapy. Hospitalization and medication utilization were also collected retrospectively by chart review for the 12-month period prior to RLAI initiation.A total of 1659 patients (mean age, 39.2; 18.3% inpatients) completed the study. Twenty-four months after initiating therapy (initial RLAI dose = 33.6 mg) 85% of patients (n = 1410) remained on RLAI (completers) while 15% discontinued therapy. The main reasons for discontinuation were insufficient response (28.5%), patient/family choice (26.1%), adverse events (9.6%) and unacceptable tolerability (6.0%). At baseline, compared to completers, discontinuers were younger (37.4 vs. 39.6 years, p = 0.01), had schizophrenia for a shorter time (10.2 vs. 11.9 years, p = 0.02), had lower Global Assessment of Functioning (GAF) scores (43.5 vs. 48.0, p = 0.0001), higher utilization of benzodiazepines (56.5 vs. 43.3%) and more initiated therapy as inpatients (30 vs. 16%). With RLAI therapy GAF scores improved significantly (p0.001) for both groups but the 24-month value for discontinuers was lower than that of completers (55.4 vs. 67.2). Compared to the pre-RLAI initiation period, at 12 months post-initiation completers had greater reductions than discontinuers in the percent of patients hospitalized (66.2% reduction vs. 29.2%) and in the length (68% reduction vs. 0%) and number (80.0 vs. 14.3%) of hospital stays, differences that remained at 24 months. The most common adverse events while patients were taking RLAI were nervous system disorders (6.8%), psychiatric disorders (5.6%), weight increase (3.2%), reproductive system and breast disorders (2.5%) and gastrointestinal disorders (2.1%).These observational data confirm that RLAI is an effective treatment in schizophrenia and high levels of adherence to therapy offers an opportunity for effective long-term disease management and significant sustained decreases in hospitalization.

The study's goal was to characterize the typology of patient outcomes based on social and occupational functioning and psychiatric symptoms following antipsychotic drug treatment, and to explore predictors of group membership representing the best/worst outcomes. A hierarchical cluster analysis was used to define groups of patients (n=1449) based on endpoint values for psychiatric symptoms, social functioning, and useful work measured up to 30 weeks of treatment. Stepwise logistic regression was used to construct predictive models of cluster membership for baseline predictors, and with 2/4/8 weeks of treatment. Five distinct clusters of patients were identified at endpoint (Clusters A-E). Patients in Cluster A (25.6%, best outcome) had minimal psychiatric symptoms and mild functional impairment, while patients in Cluster D (14.3%) and E (14.8%) (worst outcome) had moderate-to-severe symptoms and severe functional impairment. Occupational functioning, disorganized thinking, and positive symptoms were sufficient to describe the clusters. Membership in the best/worst clusters was predicted by baseline scores for functioning and symptom severity, and by early changes in symptoms with treatment. Psychiatric symptoms and functioning provided complementary information to describe treatment outcomes. Early symptom response significantly improved the prediction of outcome, suggesting that early monitoring of treatment response may be useful in clinical practice.

Objectives: To identify and evaluate the recent evidence of physical activity (PA) with or without diet counselling on cardiometabolic parameters in people who have schizophrenia. Methods: Keyword searches were used to identify articles since 2003 up to August 2009 from PubMed, SPORTDiscus, Cochrane Central Register of Controlled Trials, EMBASE, PEDro, DARE, ProQuest Dissertations and Theses and PsycINFO. There were no limitations in terms of study design and sample size. Data were extracted from each included study using key items that included participants, study design, intervention modalities, and outcome measures. Results: Thirteen studies met the inclusion criteria. Physical activity with or without diet counselling results in modest weight loss, reductions in systolic and diastolic blood pressure and decreases in fasting plasma concentrations of glucose and insulin. Identifying an optimal dose or intervention strategy for PA is not yet possible. Compliance to PA seems to be an important pr...

Background: Profile and correlates of cognitive deficits in first episode (FE) schizophrenia patients are still debated. The present study is aimed to clarify in a large sample of FIE patients the extent of impairment in key cognitive domains and its relationships with demographic and clinical variables. Method: The European First Episode Schizophrenia Trial collected demographic, clinical and neurocognitive baseline data in 498 FE patients with minimal or no prior exposure to antipsychotics. Two-hundred-twenty healthy subjects (HS) were also evaluated. Neurocognitive assessment included the Rey Auditory Verbal Learning Test: Trail Making A and B, Purdue Pegboard and Digit-Symbol Coding. Results: Patients performed worse than HS on all tests (effect sizes from - 0.88 to - 1,73). Correlations with psychopathological dimensions were weak and involved reality distortion and disorganization. The duration of untreated psychosis (DUP) was not associated with cognitive impairment. Subjects living alone had a better neurocognitive performance, while the occupation status did not reveal any association with cognition. Conclusions: A moderate/severe impairment of processing speed, motor dexterity, verbal memory and cognitive flexibility was found in the largest sample of FE patients analyzed so far. The impairment was largely independent from psychopathology and not associated with DUP. (C) 2009 Elsevier B.V. All rights reserved.

Non-adherence to pharmacological treatment leading to frequent relapses and rehospitalizations is a major issue of concern among schizophrenia patients, especially those who are recently diagnosed. Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy.To determine clinical outcomes and hospitalizations before and after the initiation of RLAI among schizophrenia patients with recent (or =2 years) diagnosis relative to those who had long-term (2 years) diagnosis.The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is an observational study of patients with schizophrenia who start treatment with RLAI. Data were recorded at baseline, retrospectively for the 12 months prior to baseline, and prospectively every 3 months for 24 months. Data on patients with a defined length of diagnosis were pooled from eight countries.Clinical Global Impression of Illness Severity (CGI-S), Global Assessment of Functioning (GAF) scores, and hospitalization data were key outcomes.The magnitude of improvement in CGI-S scores was greater in the recent versus long-term diagnosis group [Delta -1.48 vs. Delta -0.95 (12 months); Delta -1.6 vs. Delta -1.09 (24 months)]. There were parallel improvements in GAF scores [Delta 19.4 vs. Delta 13.7 (12 months); Delta 22.3 vs. Delta 16.8 (24 months)]. The decline in the proportion of patients hospitalized from the retrospective to the prospective period was greater in the recent versus long-term diagnosis group (Delta -36.0 vs. Delta -19%, respectively) at 12 months. This was also true for the number of hospital stays (Delta -0.6 vs. Delta -0.3, respectively) and length of stay (days) (Delta -20.9 vs. Delta -6.9, respectively) at 12 months. Common adverse events in both groups included psychiatric, gastrointestinal, musculoskeletal and reproductive system and breast disorders.Treatment with RLAI is associated with improved outcomes in recently diagnosed and chronic patients. However, the magnitude of improvement was higher in recently diagnosed patients.

Depression is a common mental disorder that presents with depressed mood, loss of interest or pleasure, feel- ings of guilt or low self-worth, disturbed sleep and/or appetite, low energy, and poor concentration. Depression is a wide- spread and often chronic condition. Lifetime prevalence estimates for major depressive disorder are approximately 15% to 20%; 1-year prevalence estimates are 5% to 10%. Moreover, depression is characterized by high rates of relapse: 22% to 50% of patients suffer recurrent episodes within 6 months after recovery. Depression is associated with a high incidence of co-morbid somatic illness. Individuals suffering from major depression run a higher relative risk of coronary heart disease, type 2 diabetes and osteoporosis compared with the general popula- tion. In general, depressed individuals exhibit a less active life-style and have a reduced cardio-respiratory fitness in com- parison with the general population. Strong evidence demonstrates that lack of physical activity is associated with an un- healthier body mass and composition, and a biomarker risk profile for cardiovascular disease, type 2 diabetes, and osteo- porosis. A growing body of evidence suggests that exercise is an effective treatment for depression. For mild to moderate depression the effect of exercise may be comparable to antidepressant medication and psychotherapy; for severe depres- sion exercise seems to be a valuable complementary therapy to the traditional treatments. Exercise training not only im- proves depression, but also produces 'positive side effects' on depression associated physical diseases and cognitive de- cline. We identified the meta-analyses in the area of exer- cise/physical activity and depression from 1998 until 2008. Relevant studies were identified by searching PubMed, Med- line, Sport Discus, and PsycInfo. Terms used in the search were 'depression', 'clinical depression', 'depressive symp- toms', 'exercise', 'physical activity', 'meta-analysis'. We also identified the meta-analyses and single-studies on the theme depression as an independent risk factor for develop- ment of coronary heart disease, type 2 diabetes and osteopo- rosis. All studies that investigated the role of exercise in the association among depression and these diseases were in- cluded. Finally, literature was also identified by citation tracking using reference lists from selected papers.

This study aims to identify different outcome trajectories in a psychoanalytic hospitalization-based treatment in a sample of 70 patients with personality disorders using a naturalistic 12 month follow-up design. Trajectory analysis identified four groups of patients, i.e., patients showing (a) high initial symptom levels and considerable and consistent improvement late in treatment (High-Low group; HL), (b) medium initial symptom levels and a quick and sustained response (Medium-Low group; ML), (c) medium initial symptom levels but without substantial improvement (Medium-Medium group; MM), and (d) low initial symptom levels without substantial further improvement during and after treatment (Low-Low group; LL). Further, data suggested that these four trajectories were related in theoretically meaningful ways to pre-treatment variables, such as anaclitic and introjective personality styles and trauma. Results are discussed in the context of other studies showing the need for differential treatment approaches based on pretreatment characteristics.

Objectives: There is little evidence for differences in response and speed of response to electroconvulsive therapy (ECT) between patients with bipolar and patients with unipolar depressive disorder. In the only prospective study to date, Daly et al. (Bipolar Disord 2001; 3: 95–104) found patients with bipolar depression to show more rapid clinical improvement and require fewer treatments than unipolar patients. In this study, response and speed of response of patients with unipolar and bipolar depression treated with ultra-brief pulse ECT were compared. Methods: All patients (n = 64) participated in a randomized trial comparing ultra-brief pulse bifrontal ECT at 1.5 times seizure threshold and unilateral ECT at 6 times seizure threshold. Thirteen patients (20.3%) had DSM-IV-defined bipolar depression. The Hamilton Rating Scale for Depression and Clinical Global Impression scale were administered at baseline and repeated weekly during and after the course of treatment by a blinded rater. At the same time point, the Beck Depression Inventory and the Patient Global Impression scale were administered. Speed of response was analyzed using survival analyses. Results: Patients with bipolar and unipolar depression did not differ in rates of response or remission following the ECT course, nor in response to unilateral or bifrontal ECT. Patients with bipolar depression, however, showed a more rapid response than patients with unipolar depression. Conclusions: Patients with bipolar depression tend to show more rapid clinical improvement with ECT than patients with unipolar depression.

ObjectivesThe present study aimed to (i) evaluate the association between insight and measures of executive functions and working memory in a sample of 132 patients with schizophrenia and (ii) to explore to what proportion neurocognitive dysfunction contributed to the variance in insight after controlling for symptomatology.MethodsSubjects were evaluated with a standardized neurocognitive test battery and a semi-structured interview, the Psychosis Evaluation tool for Common use by Caregivers (PECC). PECC, apart from evaluating symptoms and side-effects, measures insight on a 4-point scale by two of its dimensions: awareness of having a mental illness (AMI) and awareness of having symptoms attributed to a mental illness (ASAMI). Executive functioning was measured by the Wisconsin Card Sort Test (WCST) and the Trail Making B (TMB). Working memory was measured by the Letter Number Sequencing (LNS) test from the Wechsler Adult Intelligence Scale (WAIS).ResultsOnly one significant association was found after correction for multiple testing, between WCST categories completed and AMI (r = −0.29, p = 0.0006). WCST categories completed explained only 7.9% of the variance in AMI, while symptomatology explained 20% of variance in AMI and 16.5% of variance in ASAMI.ConclusionsThe current results show a significant but subtle association with the WCST, which is in agreement with earlier literature. No other associations between cognitive functioning and insight were found. In general, these findings seem to suggest that factors other than cognition have a greater impact on insight in patients with schizophrenia.

ObjectivesThis Schizophrenia Outcome Survey compared medical costs, psychopathology and adverse events in outpatients for 2 years following hospitalisation for an acute schizophrenic episode.MethodsAdults stabilised with haloperidol, olanzapine or risperidone entered this observational study ≤1 month after discharge and were assessed at baseline, 3, 6, 12, 18 and 24 months using Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Global Assessment of Functioning and adverse events reporting.ResultsAmong 323 patients (haloperidol 32, olanzapine 149, risperidone 142), baseline characteristics were similar in the olanzapine and risperidone groups, except for more first episodes in the risperidone group (p = 0.01). Haloperidol patients were more often single and institutionalised, less educated, had more residual schizophrenia, were longer hospitalised in the previous year, took more corrective and psychotropic drugs and had more extrapyramidal symptoms (EPS) and gynaecomastia (all significantly). Sixty-eight percent of patients completed a 2-year follow-up. In all groups, CGI and GAF improved during the first 3 months (both p < 0.0001) while BPRS deteriorated in the first year (all within group changes p < 0.05, between group changes NS) before it stabilised. There were no significant differences in hospitalisations and no change in social profile. At the last visit, 66% of haloperidol (p < 0.01), 35% of olanzapine (NS) and 39% (NS) of risperidone patients had ≥1 EPS; 69% (p < 0.013), 40 and 44%, respectively, had ≥1 sexual problem (NS). Mean weight gain was 0.4 (NS), 2.6 (p < 0.05) and 2.6 kg (p < 0.05), respectively.ConclusionsIn this naturalistic study, treatment allocation might have introduced a bias in the interpretation of efficiency results, but olanzapine and risperidone caused less EPS than haloperidol during 2 years of outpatient follow-up.

Objective: Acute aerobic exercise is associated with a reduction in state anxiety and an improvement in subjective well-being. The objective of the present study was to contrast the effects of aerobic exercise at self-selected intensity versus prescribed intensity on state anxiety and subjective well-being (negative affect, positive well-being and fatigue) in patients with depressive and/or anxiety disorders. In addition, the potential impact of heart rate feedback was assessed. Methods: Nineteen men and 29 women performed three test conditions on a bicycle ergometer during 20 minutes: two tests at self-selected intensity; one with and another without heart rate feedback, and a third test at the prescribed intensity of 50% of the maximal heart rate reserve according to Karvonen. Tests were executed in random order. State anxiety and subjective well-being were evaluated using the state anxiety inventory and the subjective exercise experiences scale. Results: After 20 minutes cycling, patients showed significantly decreased state anxiety and negative affect in the three conditions. The magnitude of the reduction did not differ significantly between the three conditions. Only cycling at self-selected intensity enhanced positive well-being. Cycling at 50% of the maximal heart rate reserve decreased fatigue, whereas cycling at self-selected intensity increased fatigue. Conclusions: The response in state anxiety and negative affect was unaffected by the type of aerobic exercise. Self-selected intensity influenced exercise-induced changes in positive well-being and fatigue in a positive and negative way, respectively.

OBJECTIVE: Unconfounded differences in inherent vulnerability to metabolic disturbance may be hypothesized for different diagnostic groups with severe mental illness. METHOD: A naturalistic cohort of patients diagnosed with DSM-IV bipolar disorder (N = 112), schizophrenia (N = 503), and schizoaffective disorder (N = 92) were assessed for metabolic disturbances. The prospective inclusions started in November 2003 and were concluded in July 2007. RESULTS: Diagnosis was strongly associated with the metabolic syndrome (chi(2) = 14.90, df = 2, p < .001). Compared with bipolar patients, the unadjusted risk for metabolic syndrome was significantly higher for schizoaffective (odds ratio [OR] = 3.51, p < .0001) but not for schizophrenia patients (OR = 1.58, p = .094). Differences were not reducible to confounding factors including treatment. Rather, the difference between bipolar and schizophrenia patients also reached significance after adjustment (OR = 1.97, p = .046). Furthermore, the association between diagnosis and glucose dysregulation was significant (chi(2) = 6.97, df = 2, p = .031), with a significantly higher risk in schizoaffective (unadjusted OR = 2.12, p = .022) but not in schizophrenia patients (unadjusted OR = 1.13, p = .640) compared with bipolar patients. Diagnostic differences in glucose dysregulation were in part mediated by body mass index (BMI). CONCLUSIONS: Schizoaffective patients in particular may be at risk for metabolic disturbances compared with bipolar and schizophrenia patients. Differences were not reducible to known metabolic risk factors and could only be explained in part by higher BMI in schizoaffective patients, suggesting an increased inherent vulnerability in this group. ispartof: Journal of Clinical Psychiatry vol:69 issue:8 pages:1319-1327 ispartof: location:United States status: published

Objectives: The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in disorders other than schizophrenia in which antipsychotic medication is part of routine treatment. Methods: Sixty consecutive patients with bipolar disorder (BD) at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test. The prevalence of the metabolic syndrome was assessed based on the National Cholesterol Education Program Adult Treatment Protocol (ATP-III) criteria, the adapted ATP-III criteria using a fasting glucose threshold of 100 mg/dL, and the recently proposed criteria from the International Diabetes Federation (IDF). Results: The analysis of 60 patients showed a prevalence of the metabolic syndrome of 16.7% (ATP-III), 18.3% (adapted ATP-III) and 30.0%) (IDF), respectively. A total of 6.7% of the patients met criteria for diabetes and 23.3% for pre-diabetic abnormalities. Conclusions: The metabolic syndrome and glucose abnormalities are highly prevalent among patients with BD. They represent an important risk for cardiovascular and metabolic disorders. Assessment of the presence and monitoring of metabolic abnormalities and its associated risks should be part of the clinical management of patients with BD.

Background: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. Methods: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. Findings: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0·37, [95% CI 0·24-0·57]), olanzapine (HR 0·28 [0·18-0·43]), quetiapine (HR 0·52 [0·35-0·76]), and ziprasidone (HR 0·51 [0·32-0·81]). However, symptom reductions were virtually the same in all the groups, at around 60%. Interpretation: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement. Funding: AstraZeneca, Pfizer, Sanofi-Aventis. © 2008 Elsevier Ltd. All rights reserved.

Although the concept of remission has been widely accepted and utilized in depression and anxiety disorders, there has been much less emphasis on defining remission in schizophrenia. Recently, an expert consensus definition of remission in schizophrenia was proposed along specific operational criteria for the attainment of remission focusing on the three core dimensions of psychopathology identified within schizophrenia: psychoticism, disorganization and negative symptoms. To date, the criteria have been applied retrospectively to several clinical studies, and these have demonstrated that the proposed definition of remission correlates significantly with established measures of symptom severity, functioning and quality of life, and appears achievable for a significant proportion of patients receiving at least 3 months of pharmacotherapy. In this article we extend the notion of remission to include an examination of the possible association of several modifiable and unmodifiable factors and co-morbidities on remission status. We also propose an investigation into the likelihood of different patient populations in achieving remission as well as assessing the impact of remission on health care costs and family burden. Since cognitive dysfunction and negative symptoms may be strongly correlated with a lower likelihood of achieving remission, we recommend retrospective and/or prospective studies to determine the relationship between neurocognitive status and the predominance of negative symptoms at treatment start and the probability of achieving remission. Taken together, these studies should help identify key predictors of remission, further define the remitted state, reduce therapeutic pessimism, raise treatment expectations and chart a strategy for further research in this important area.

This naturalistic study aims to evaluate the influence of antipsychotic treatment on the use of anticholinergics. The observed use of anticholinergics will give an indication of the occurrence of extrapyramidal side effects (EPS) in the different antipsychotic treatment conditions. The medication use of 1215 hospitalised patients with DSM-IV 295.xx diagnosis is recorded. Four antipsychotic treatment conditions are distinguished: 1) only first generation antipsychotics (FGA): patients receive one or a combination of first generation antipsychotics, 2) a combination of high potency FGA and second generation antipsychotics (SGA), 3) a combination of low potency FGA and SGA, and 4) only SGA: patients receive one or a combination of SGA. Antipsychotic treatment significantly influences the use of anticholinergics. Anticholinergic use is highest in patients treated with high potency FGA (whether or not in combination with SGA) as compared with patients only treated with SGA and patients combining SGA with low potency FGA. The two latter groups do not significantly differ. However, there were no significant differences in the prevalence of EPS with the exception of akathisia between FGA and SGA. Thus, through the use of anticholinergics, EPS induced by FGA can be effectively reduced.

Objective: The presence of a prospective association between cognition and functional outcome in first episode patients with schizophrenia is much debated. Method: Associations between Intelligence Quotient (IQ) measures and functional outcome were assessed at the first hospitalization and after 10 years follow-up. Results: Functional outcome was associated with estimated premorbid IQ and IQ at 10-year follow-up, but not with IQ assessed at first hospitalization. Conclusion: The presence of a prospective as well as a cross-sectional relationship of the global cognitive measure IQ with 10-year functional outcome could be established. However, assessing associations between cognitive measures assessed at first hospitalization and subsequent functional outcome, can give inconclusive results due to non-uniform intellectual deterioration from premorbid level in the period preceding the first hospitalization.

The use of certain atypical antipsychotics has been associated with metabolic disturbances. We have assessed the evolution of body weight and glycaemia during a 6-month randomized comparative trial of amisulpride and olanzapine. Three hundred and seventy-seven adult patients with schizophrenia were randomized to either amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. Body weight and fasting blood glucose were measured. Both treatments showed comparable antipsychotic activity. Weight gain over the study was significantly greater (P=0.0004) in the olanzapine group (3.9+/-5.3 kg) than in the amisulpride group (1.6+/-4.9 kg). Mean fasting blood glucose increased in the olanzapine group by 4.42 mg/dl to a mean maximum value (118+/-38 mg/dl). In the amisulpride group, mean glucose levels fell by 2.82 mg/dl. The difference between groups was significant at 2 (P=0.0066) and 6 months (P=0.017). One olanzapine-treated patient was diagnosed with diabetes. Metabolic changes in the amisulpride group were restricted to patients with high body mass index at inclusion. At doses that provide comparable control of psychosis, treatment with olanzapine was associated with greater increase in weight and blood glucose compared with amisulpride. This should be taken into account in assessing risk-benefit of treatment options in schizophrenia.

To evaluate the relationship of dose decrease, symptom worsening, and baseline covariates on subsequent relapse during olanzapine treatment in patients with schizophrenia or schizoaffective disorder.In two 28-week, randomized, double-blind clinical trials, a Cox proportional hazards model was used to determine potential correlates of relapse (defined asor =20% worsening on PANSS total and CGI-Severity 3) among patients (N=271) who responded to 8 weeks of olanzapine treatment (10-20mg/day). Variables examined included: demographics, illness characteristics, baseline symptoms, symptom change, dose, adverse events, and functioning.Patients with a lower last dose relative to the preceding visit interval were 4 times more likely to relapse during that visit interval than other patients (p.001). A similar finding was observed for a decrease in interval modal dose, although this variable was more predictive of relapse in the visit interval immediately following dose decrease (p=.027). In a subgroup analysis by gender, there was a significantly greater incidence of relapse in men with a dose decrease, whereas a dose decrease in women did not correlate with relapse. Relapse was also correlated with the emergence or worsening of a psychiatric adverse event during the same (p.001) and preceding (p=.007) visit intervals, and with increased rating scale measures of psychopathology. The occurrence of a non-psychiatric adverse event was not associated with relapse.Dose decrease is a significant predictor of relapse in male but not female patients. Psychiatric adverse events also predicted relapse. Patients should be periodically reassessed to determine the need for maintenance treatment with appropriate dose.

Contains fulltext : 56927.pdf (Publisher’s version ) (Closed access) To study action monitoring in anorexia nervosa, behavioral and EEG measures were obtained in underweight anorexia nervosa patients (n = 17) and matched healthy controls (n = 19) while performing a speeded choice-reaction task. Our main measures of interest were questionnaire outcomes, reaction times, error rates, and the error-related negativity ERP component. Questionnaire and behavioral results indicated increased perfectionism in patients with anorexia nervosa. In line with their perfectionism and controlled response style patients made significantly less errors than controls. However, when controlling for this difference in error rates, the EEG results demonstrated a reduced error-related negativity in the patient group. These seemingly contradictory outcomes of improved performance and reduced error monitoring are discussed in relation with indications of anterior cingulate cortex hypoactivity in anorexia nervosa patients. 9 p.

Background A regulatory signal suggested that sertindole was associated with a 10-fold increased risk of death. This observational study aimed to identify deaths and their causes in patients treated with sertindole. Methods Sertindole-treated patients in Germany, Austria, Belgium, Hungary, The Netherlands and the United Kingdom were identified and their vital status ascertained. Eventual cause of death and patient and treatment characteristics were ascertained. A nested case-control study compared on-treatment cardiac or unexplained deaths with randomly selected survivors matched on age and gender for potential risk factors. Results Eight thousand six hundred eight patients were identified as having initiated treatment with sertindole, for a total 3819 person-years exposure. Thirty-five had died since (all-cause mortality rate 0.92 per 100 person-years exposed). Of these, 15 (43%) had been previously reported to the regulatory authorities. Eight deaths were suicides, of which 2 (25%) had been previously reported; 11 were cardiac deaths, of which 8 (73%) had been reported. On average, patients who died because of cardiac disorders were older, and patients who committed suicide were younger than the other patients who died. The nested case-control study revealed that patients receiving sertindole were at a higher risk of premature cardiac or unexplained death if they had hypertension or other cardiovascular disorders associated with diabetes or metabolic disorder. Conclusion Overall and cardiovascular death rates were similar or lower than those observed in premarketing clinical trials. There was a very high reporting rate of all-cause and cardiovascular deaths that could have contributed to the regulatory alert. Copyright © 2007 John Wiley & Sons, Ltd.

Background: Metabolic abnormalities and weight gain are an important problem in patients with schizophrenia. An instrument to evaluate body image and self-esteem related to weight has recently been developed (B-WISE®). The first objective was to evaluate whether the findings of the original validation study could be confirmed in a European sample. The second objective was to explore the association of B-WISE® scores with the metabolic syndrome and glucose abnormalities. Methods: A Dutch translation of B-WISE® was tested in a large sample of patients with schizophrenia (n=300) who underwent an extensive metabolic screening. Results: The original findings with B-WISE® were confirmed in an independent sample. Scores on B-WISE® differed significantly as a function of BMI. Scores on B-WISE® also differentiated patients with and without the metabolic syndrome and glucose abnormalities. Patients experiencing a recent weight gain had lower self-esteem and poorer psychosocial adaptation. Conclusion: B-WISE® could be a useful instrument to evaluate the subjective psychosocial consequences associated with current weight and weight gain in patients with schizophrenia.

The aim of the present study was to examine the longitudinal course of IQ and its heterogeneity in patients with schizophrenia, from the perspective of the two main "subtypes" of schizophrenia described in the literature: progressive cognitive deficit versus cognitive stabilisation or recovery. Premorbid IQ scores and WAIS IQ scores of 100 first onset patients were obtained at first hospitalization (T1) and after 10 years (T2). Significant changes in IQ over time were found, representing (i) at T1, a deterioration compared to premorbid intelligence (B=-6.3, 95% CI -9.5 to -3.0, p

Velen veronderstellen dat bij patienten met anorexia nervosa cognitieve processen gestoord zijn, waarschijnlijk omdat zij er zulke vreemde opvattingen op na houden over hun gewicht en hun voorkomen. Zij zouden cognitieve beperkingen hebben zolang ze mager zijn. Dit hebben wij onderzocht. Patienten werden getest met kopieertaken. Deze werden afgenomen bij sterk ondergewicht en na gewichtsherstel. Bovendien werden ze afgenomen bij controleproefpersonen. In de kopieertaken vertoonden de anorexiapatienten kortere reactietijden dan de controles, zowel bij uitgesproken ondergewicht als na gewichtsherstel. We vonden dus geen aanwijzingen voor cognitieve tekorten, gerelateerd aan executief functioneren, bij anorexia-nervosapatienten. Patienten vertoonden aanwijzingen voor superieure planning en sequencing-capaciteit, zowel bij uitgesproken ondergewicht als na gewichtsherstel. Deze bevindingen zijn in overeenstemming met de hypothese dat een sterke cognitieve activering, een ‘mentale bewegingsdrang’, karakteristiek is voor acute anorexia nervosa.

Objective The purpose of this study was to investigate the “extent of information desired” (EID)-scale through a behavioural approach. Methods Standardised interviews consisting of the EID-scale and four (half) open questions were conducted in a convenience sample of psychiatric in-patients and information seeking behaviour was measured. At the same time, socially desirable behaviour was assessed by means of Marlowe–Crowne social desirability (MCSD). Results 39 patients were interviewed. The behavioural approach yielded mixed results, but there was no correlation between EID- and MCSD-scores. Discussion From the calculated correlations information seeking behaviour is perceived as socially undesirable, whereas EID-scores seem unaffected by social desirability. Conclusion It is difficult to define independent variables which would reflect information seeking behaviour. The ones we used might have been confounded. We found a correlation between the EID-scale used and the information seeking behaviour, without a strong correlation with social desirability. Practice implications The EID-scale used may predict patients’ desire for information within a well-defined clinical context. The step to validation requires more robustness of the research model and a better profiling of patients.

Contains fulltext : 56419.pdf (Publisher’s version ) (Closed access) Objectives A vast amount of studies demonstrates the presence of psychomotor slowing in schizophrenia. The objective of the present study was to investigate whether this overall psychomotor slowing can be divided into distinct processes that differentially affect cognitive functioning in schizophrenia. Methods The pen-tip movements of 30 schizophrenic inpatients and 30 matched controls were digitally recorded during performance of the Symbol Digit Substitution Test (SDST) and analysed to differentiate matching time and writing time, representing the cognitive and sensorimotor component of slowing, respectively. In addition, the results were compared to each other and to the scores of traditional neuropsychological tests that assess domains such as memory and attention. Results Both matching time and writing time were longer in the schizophrenic patients relative to the controls but did not correlate. Only matching time correlated significantly with the conventional neuropsychological test results. Conclusions Although schizophrenic patients display both sensorimotor and cognitive slowing, the two processes are unrelated. Furthermore, only the cognitive component was associated with most of the cognitive deficits as measured by traditional neuropsychological tests. 7 p.

Objective: Recent work has focussed on schizophrenia as a ‘deficit’ state but little attention has been paid to defining illness plasticity in terms of symptomatic remission. Method: A qualitative review of a recently proposed concept of remission [N.C. Andreasen, W.T. Carpenter Jr, J.M. Kane, R.A. Lasser, S.R. Marder, D.R. Weinberger (2005) Am J Psychiatry 162: 441] is presented. Results: The proposed definition of remission is conceptually viable, and can be easily implemented in clinical trials and clinical practice. Its increasing acceptance may reset expectations of treatment to a higher level, improve documentation of clinical status and facilitate dialogue on treatment expectations. The availability of validated outcome measures based on remission will enhance the conduct and reporting of clinical investigations, and could facilitate the design and interpretation of new studies on cognition and functional outcomes. While useful as a concept, it is important to consider that remission is distinct from recovery. Conclusion: The introduction of standardized remission criteria may offer significant opportunities for clinical practice, health services research and clinical trials.

Objective To assess the diagnostic properties of 2 different screening guidelines for the detection of diabetes in patients diagnosed with schizophrenia. Method Over a 2-year period (November 2003-November 2005), 415 patients with schizophrenia were screened with a full laboratory screening and a 75-g oral glucose tolerance test (OGTT). The sensitivity of 2 screening strategies was compared with the "gold standard": the OGTT. The 2 strategies were (1) assessing fasting glucose in all patients, as suggested by the American Psychiatric Association/ American Diabetes Association (APA/ADA), and (2) a screening strategy derived from the guidelines of the World Health Organization of assessing fasting glucose in all patients (step 1) and subsequently performing an OGTT in patients with impaired fasting glucose (step 2). Results Of the total sample, 6.3% (N = 26) met criteria for diabetes, resulting in a mean annual incidence of diabetes of 3.15% (6.3% incident cases/2 years). A screening based on the APA/ADA guidelines detected diabetes in 12 (46.2%) of the 26 cases identified by the OGTT. The proposed 2-step strategy detected 25 (96.2%) of 26 cases. Conclusion The data suggest a high incidence of diabetes in patients diagnosed with schizophrenia. However, the guidelines to detect diabetes as proposed by the APA/ADA did not sufficiently detect diabetes in this specific high-risk group. The alternative 2-step strategy was able to detect the vast majority of diabetes cases and should therefore be considered in the clinical routine of screening and monitoring patients with schizophrenia.

The presence of the metabolic syndrome is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic syndrome in European patients suffering from schizophrenia. Methods All consecutive patients with schizophrenia at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test. The prevalence of the metabolic syndrome was assessed based on the National Cholesterol Education Program criteria (NCEP, Adult Treatment Protocol, ATP-III), adapted ATP-III criteria using a fasting glucose threshold of 100 mg/dl (AHA) and on the recently proposed criteria from the International Diabetes Federation (IDF). Results The analysis of 430 patients showed a prevalence of the metabolic syndrome of 28.4% (ATP-III), 32.3% (ATP-III A) and 36% (IDF), respectively. The prevalence of the metabolic syndrome in our sample of patients with schizophrenia is at least twice as high compared to an age-adjusted community sample in Belgium. Conclusion The metabolic syndrome is highly prevalent among treated patients with schizophrenia. It represents an important risk for cardiovascular and metabolic disorders. Assessment of the presence and monitoring of the associated risks of the metabolic syndrome should be part of the clinical management of patients treated with antipsychotics.

Background Mortality rates in patients with schizophrenia are double compared to those in the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein (LDL) cholesterol is recognized as a primary target for the prevention of cardiovascular mortality according to the National Cholesterol Education Program-Adult Treatment Panel III. Use of lipid-lowering drugs such as statins is recommended when lifestyle changes are not sufficient to reach the LDL goal. The efficacy and safety of rosuvastatin treatment were evaluated in schizophrenic patients. Method 100 schizophrenic patients with severe dyslipidemia were identified. All were treated with antipsychotics. Fifty-two patients were treated with rosuvastatin and compared with 48 who did not receive statin treatment. All patients were screened for cardiovascular risk factors and examined at baseline. The effects of lipid-lowering medication on lipid profile, glucose homeostasis, and components of metabolic syndrome were evaluated at 3-month follow-up. The study began in 2003, and all data available until December 2005 are reported. Results After 3 months of statin therapy, a significant decrease in triglycerides, total cholesterol, LDL cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol and in associated ratios (LDL/HDL, total cholesterol/HDL) was observed. The difference was highly significant compared to patients not receiving statin treatment. No significant changes occurred in HDL cholesterol, body mass index and waist circumference, or glucose homeostasis. The only component of metabolic syndrome affected by statin therapy was the serum triglyceride level. Conclusion Rosuvastatin proved effective in the management of dyslipidemia in patients with schizophrenia treated with antipsychotics. More complex treatment may be required for associated metabolic disturbances.

We sought to determine the degree of satisfaction with bifrontal and right unilateral electroconvulsive therapy (ECT) and to investigate the relation with treatment-related variables, such as memory complaints, and patient-related variables, such as self-rated depression severity and negative affectivity.Subjects included all patients who started a course of ECT between May 2001 and December 2003, or still were receiving continuation or maintenance ECT (C/M-ECT) at the time of the study. A psychiatric nurse that was not a member of the treatment team conducted semi-structured interviews based on a battery of questionnaires (Patient Satisfaction Survey [PSS], Mini-Mental State Examination [MMSE], Squire Subjective Memory Questionnaire [SSMQ], Beck Depression Inventory [BDI], and Positive and Negative Affect Schedule [PANAS]).Of 50 eligible subjects, 36 (72%) completed the survey. Fourteen patients refused to participate. At the time of the interview, 19 patients (52.8%) were hospitalized, and 14 (38.9%) were receiving C/M-ECT. The mean time between last treatment session and interview was 282 days. Diagnostic categories were depressive disorder (50%) and psychotic disorder (47.2%). Bifrontal electrode position was used in 25 (69.4%) of the study patients and unilateral in 4 (11.1%). Patients had a considerable degree of satisfaction (mean PSS 153.41; SD 16.29), although they had prominent cognitive complaints (mean score SSMQ -11.86; SD 21.30). In a multiple regression model, in which satisfaction was predicted on the basis of age, sex, and scores on BDI, SSMQ, PANAS, and GAF, only the GAF-score at the time of the interview was significantly related to satisfaction. All other predictors were not significant.Patients receiving bifrontal or right unilateral ECT do have considerable memory complaints, even a long time after their treatment. However, the degree of these complaints does not seem to predict satisfaction with the treatment. Only 38% of the variance of satisfaction could be predicted on the basis of age, sex, BDI, SSMQ, Negative Affectivity subscale of the PANAS, and GAF-scores, which proves that satisfaction with ECT is based on other factors than just the relief of symptoms or the occurrence of side-effects. The factors that contribute to patients' satisfaction remain largely unknown.