M.P. García-Portilla

Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study

OBJECTIVES The aim of this cross-sectional study, the EIRE study, was to assess the frequency of several side effects with antipsychotics in the clinical setting. This paper addresses the adverse effect of weight gain. METHOD Outpatients diagnosed of schizophrenia according to DSM-IV criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. Data were collected in a single visit, including data on demographic, clinical and treatment characteristics. Mean weight change was evaluated retrospectively by means of clinical charts and the weight at the time of the visit; in addition, the corresponding item of a modified version of the UKU, a Scandinavian side-effect rating scale, was used. Chi-squared test and logistic regression methods were used to analyze frequency of weight gain between treatments. RESULTS Out of 669 recruited, 636 evaluable patients were assessed. The treatment with the highest number of patients with weight gain as an adverse reaction on the UKU scale was olanzapine (74.5%), followed by risperidone (53.4%) and haloperidol (40.0%). The proportion of patients with clinically relevant weight gain (>or=7% increase versus initial weight) was also higher with olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%). Five patients (13.5%) treated with quetiapine had some degree of weight gain according to the UKU scale, although no patient showed a clinically relevant weight gain (>or=7%). Treatment with olanzapine and risperidone were identified as risk factors of weight gain versus haloperidol. The risk of weight gain was higher in women (OR: 4.4), overweight patients (OR: 3.0) and in patients with <or=1 year of treatment (OR: 6.3) in the olanzapine group. A higher risk of weight gain in women (OR: 2.6) was also seen with risperidone. CONCLUSION Clinically relevant weight gain is clearly associated with olanzapine, and to lesser extent, with haloperidol and risperidone. Data for quetiapine were not conclusive because of the short duration of treatment.

Predictive factors of functional capacity and real-world functioning in patients with schizophrenia

PURPOSE This study was performed to identify the predictive factors of functional capacity assessed by the Spanish University of California Performance Skills Assessment (Sp-UPSA) and real-world functioning assessed by the Spanish Personal and Social Performance scale (PSP) in outpatients with schizophrenia. METHODS Naturalistic, 6-month follow-up, multicentre, validation study. Here, we report data on 139 patients with schizophrenia at their baseline visit. ASSESSMENT Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), Sp-UPSA and PSP. STATISTICS Pearsons correlation coefficient (r) was used to determine the relationships between variables, and multivariable stepwise linear regression analyses to identify predictive variables of Sp-UPSA and PSP total scores. RESULTS Functional capacity: scores on the PSP and PANSS-GP entered first and second at P<0.0001 and accounted for 21% of variance (R(2)=0.208, model df=2, F=15.724, P<0.0001). Real-world functioning: scores on the CGI-S (B=-5.406), PANSS-N (B=-0.657) and Sp-UPSA (B=0.230) entered first, second and third, and accounted for 51% of variance (model df=3, F=37.741, P<0.0001). CONCLUSION In patients with schizophrenia, functional capacity and real-world functioning are two related but different constructs. Each one predicts the other along with other factors; general psychopathology for functional capacity, and severity of the illness and negative symptoms for real-world functioning. These findings have important clinical implications: (1) both types of functioning should be assessed in patients with schizophrenia and (2) strategies for improving them should be different.

Cognitive Performance associated to functional outcomes in stable outpatients with schizophrenia

Background–objective Prevalence data of cognitive impairment in Schizophrenia based on large population samples are scarce. Our goal is to relate cognition and functional outcomes, and estimate prevalence of cognitive impairment in a large sample of schizophrenia outpatients treated with second-generation antipsychotics. Method A cross-sectional outpatient evaluation conducted during follow-up visits. Selection criteria included six-months stable treatment. The brief battery, EPICOG-SCH, covered four cognitive domains related to functional outcomes: working memory (WAIS-III-Letter-Number-Sequencing), executive function (Category Fluency Test; CFT), verbal memory (WMS-III-Logical-Memory), and information processing speed (Digit-Symbol-Coding and CFT). Clinical severity and functional impairment were assessed with CGI-SCH and WHO DAS-S. Impairment prevalence was calculated at ≤ 1.5 SD. Results Among patients recruited (n = 848) in 234 participating centers, 672 were under 6-month treatment. 61.5% (n = 413) reported cognitive impairment according to CGI-SCH Cognitive Subscale. Estimated prevalences were 85.9% (95% CI 85.6–86.2%) CFT-Fruits; 68.3% (95% CI 67.8–68.8%) CFT-Animals; 38.1% (95% CI 37.5–38.3%) Digit-Symbol-Coding; 24.8% (95% CI 24.1–25.5%) Verbal Memory-Units; 20.9% (95% CI 20.2–21.6%) Letter-Number Sequencing; 11.7% (95% CI 11.0–12.4%) Verbal Memory-Items. Negative and Depressive symptoms, Deficit Syndrome, and functional disability were related to poor performance. Functional disability was predicted by CGI-SCH-Overall severity (OR = 1.34635, p < 0.0001), CGI-SCH-Negative Symptoms (OR = 0.75540, p < 0.0001), working memory (Letter-Number-Sequencing) (OR = − 0.16442, p = 0.0004) and the time-course (OR = 0.05083, p = 0.0094), explaining 47% of the observed variability. Conclusion Most prevalent impairments were on executive function and processing speed domains; however, working memory showed the strongest relationship to functional disability. Monitoring cognitive function during follow up is critical to understand patient’s everyday functional capacity.

Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls

BACKGROUND Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear. MAIN AIM To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC). METHODS Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)]. STATISTICAL ANALYSIS ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD. RESULTS Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040). CONCLUSIONS This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.

Frequency of extrapyramidal adverse reactions in schizophrenic outpatients treated with risperidone, olanzapine, quetiapine or haloperidol: Results of the EIRE Study

ObjectiveThe EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia — Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions.Patients and study designOutpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser — Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ2) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used.Results636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ2: p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ2: p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ2: p < 0.05). Olanzapine, quetiapine and risperidone also showed a lower risk of EPS than haloperidol when adjusting by dose.ConclusionOur results suggest that the atypical antipsychotics studied are less likely to induce extrapyramidal adverse reactions compared with haloperidol in stabilised patients, although these reactions are still common.

Early versus late stage schizophrenia. What markers make the difference

Abstract Objectives: To identify the psychopathological, cognitive, functional, physical health and inflammatory markers that differentiate between early-stage schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). Methods: Cross-sectional, naturalistic study of 104 patients with SCH. The sample was divided in two groups: 35 ESSCH (≤7 years’ duration of illness) and 69 LSSCH (>10 years’ duration of illness). Statistical analysis: chi-square test and Students t-test and ANCOVA (or Quade test) controlling for age, sex, BMI and number of cigarettes/day. Finally, a binomial logistic regression was made. Results: ESSCH show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of IκBα (F = 7.644, p = 0.007), were more frequently classified as normal weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic regression model included age (B = 0.127, p = 0.001) and IκBα (B = 0.025, p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square =41.841, p < 0.0001). Conclusions: Age and IκBα are the unique markers that differentiate between ESSCH patients whose duration of illness is less than 7 years and LSSCH patients. These results support the hypothesis of toxicity of episodes and highlight the importance of preventing new episodes.

Treatments for Opioid Dependence and Methadone: Neurological and Behavioral Aspects

Abstract This chapter is focused on opioid dependence treatment and is framed in a holistic perspective. Specifically, there are three main approaches to pharmacological treatment of opioid dependence: opioid detoxification, agonist maintenance, and antagonist maintenance. There is a great amount of evidence supporting the efficacy of methadone and buprenorphine or the combination of buprenorphine–naloxone for the treatment of opioid withdrawal and their clinical utility as pharmacotherapy in long-term maintenance programs. Secondary or adjunctive medications such as heroin, naltrexone, and alpha-2-adrenergics are also reviewed. The need for further research and to overcome nonscientifically based barriers that prevent from developing and improving treatment resources, and the importance of managing comorbidity with other substances as well as other psychiatric illnesses, is briefly discussed.

P.3.f.023 - EPICOG-SCH − a brief cognitive battery to monitor stable outpatients with schizophrenia

Background and Purpose: Cognition and functional outcomes in schizophrenia have been largely studied. Our aim was to validate and describe the usefulness of EPICOG-SCH brief battery to monitor patient’s cognitive status in Mental Health Settings. Method: A cross-sectional outpatient evaluation was conducted during follow-up visits. Selection criteria included six-months of stable treatment with second generation antipsychotics. EPICOGSCH battery covered four cognitive domains related to functional outcomes as described in the literature: working memory, executive function, verbal memory and information processing speed. Subtests included WAIS-III-Letter-Number-SequencingLNS), Category Fluency Test-CFT, WMS-III-Logical-MemoryLM Immediate Recall, and WAIS-III-Digit Symbol Coding-DSC. Clinical Severity and Functional Impairment was assessed with CGI-SCH and WHO DAS-S, respectively. Cognitive impairment prevalence was calculated at 1.5 SD or Percentil 10 using published normative data. Composite scores based on Unitary Sum of Scores (UCS) based on scalar scores and Functional Weighted Composite Score (FWCS) based on regression analysis using WHO DAS-S [1], were calculated. A more patient-focused summary scores included domain Relative Indexes, as measure of patient’s cognitive resources involved during battery performance, and domain Absolute Indexes, as measure of patient cognitive status on each domain. UCS relationship to patient’s sociodemographic and functional factors are presented. Results: Among recruited patients (n = 848) in 234 participating centers, 6-month stable drug treatment was confirmed in 672 patients. According to CGI-SCH Cognitive Subscale, 61.5% (n = 413) were reported to have impairment. Based on cognitive testing, the highest prevalence was observed for CFT-Animals 68.3%, followed by DSC 38.1%, LM-Units 24.8% and LNS 20.9%, with the lowest prevalence for LM-Issues 11.7% [2]. No differences on prevalence among gender were found but for LM-Issues estimated prevalence 13.7% for men and 8.1% for women (p = 0.0125). Gender differences were mainly found at low limit performance levels (i.e. 1 SD) on DSC (p = 0.0241), LMUnits (p = 0.019), LM-Issues, (p = 0.0033). EPICOG-SCH battery showed a good internal consistency, Chronbac Alpha 0.78. Derived battery composite score UCS showed also similar performance among men and women (p = 0.8115). Significantly higher scores were observed on younger patients (p< 0.0001, Effect SizeES = 0.68), on those with higher educational level (p< 0.0001, ES = 1.78), with Active work situation (p< 0.0001, ES = 0.50), with higher Professional Level (p< 0.0001, ES = 0.47) or on those enrolled on Educational Programs (p< 0.0001, ES = 0.92). Regarding clinical factors, more severely ill patients, as measured by CGI-SCH subscales, showed lower cognitive performance, and also those presenting Deficit Syndrome (p< 0.0009, ES=-0.61). Anticholinergic treatment was also significantly related to lower performance (p< 0.0001, ES=-0.42), as well as Non-Adherence to antipsychotic treatment (p< 0.0041, ES=-0.32), or low Treatment Satisfaction (p< 0.0001, ES=-0.30). UCS was also inversely correlated to Severity on CGI-SCH Cognitive Subscale at r = 0.4, p< 0.0001 and CGI-SCH Negative Symptoms subscale at r = 0.4, p< 0.0001. Conclusions: EPICOG-SCH brief battery is a valid tool to evaluate schizophrenia patients during clinical stability periods; it provides useful providing information about cognitive status in schizophrenia key domains. Battery composite score (UCS) showed association to patient’s sociodemographic and to clinical features. Longitudinal studies are needed to evaluate stability over time and sensitivity to change.

EPA-0781 – Psychopathology and pattern of tobacco use in patients with schizophrenia.

Introduction The self-medication hypothesis proposes that schizophrenia patients may smoke as an attempt to reduce their cognitive deficits, their symptoms or the antipsychotic side-effects. Aim to identify the relationship between the smoking topography and psychopathology among outpatients with DSM-IV schizophrenia. Method The sample included 26 smoking outpatients with DSM-IV schizophrenia from a Mental Health Center sited in the North of Spain [65.5% males; mean age (SD) = 44.66 (7.83)]. Instruments: (1) Psychopathology: Positive and Negative Syndrome Scales (PANSS); Clinical Global Impression of Severity (CGI-S); n° antipsychotic. (2) Pattern of tobacco use: n° cigarettes/day; Fargerstrom test for nicotine physical dependence; Glover-Nilsson test for nicotine psychological dependence; Expired carbon monoxide (CO ppm). Results prevalence was 59.3% for non-heavy smokers [ Conclusion In this sample of schizophrenia patients, there is no relation between the severity of psychopathology and the dependence of nicotine. However, the sample of this study is small.

EPA-0492 - Functional remediation in bipolar II patients: improvement of functioning and subsyndromal symptoms

Introduction Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. Objective Our objective was to test the efficacy of FR programme in a subsample of euthymic bipolar II patients (BPII). Aims The main aim was improve the functional outcome in these patients. Method Post-hoc analyses were undertaken using data of 53 DSM-IV diagnosed BPII outpatients who had participated in a multicentre, rater blind, randomized, controlled trial (RCT) exploring the efficacy of FR (n=17) as compared with a Psychoeducation (PSY) (n=19) and a control (n=17) groups which only treatment as usual (TAU). The primary outcome variable was a functional improvement measured as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after intervention. Results Data revealed a significant functional improvement from baseline to endpoint (Pillais Trace =0.164; F =3.619; p =0.037), suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukeys post-hoc test only revealed a trend in favour of a better outcome for FR when compared to the TAU (p =0.058) and to the PSY group (p =0.062). We also found an interaction between program pertinence and time when analysing the subdepressive symptoms (Pillais Trace =0.157; F =3.635; p =0.036), so that patients in FR showed a significant reduction in subdepressive symptomatology when compared to the PSY group (p= 0.041). Conclusions The FR program appears to be effective in improving the overall functional outcome in BPII patients, as well as in reducing subdepressive symptoms.